sample research paper chapter 1 to 3

What’s Included: Research Paper Template

If you’re preparing to write an academic research paper, our free research paper template is the perfect starting point. In the template, we cover every section step by step, with clear, straightforward explanations and examples .

The template’s structure is based on the tried and trusted best-practice format for formal academic research papers. The template structure reflects the overall research process, ensuring your paper will have a smooth, logical flow from chapter to chapter.

The research paper template covers the following core sections:

The title page/cover page
Abstract (sometimes also called the executive summary)
Section 1: Introduction
Section 2: Literature review
Section 3: Methodology
Section 4: Findings /results
Section 5: Discussion
Section 6: Conclusion
Reference list

Each section is explained in plain, straightforward language , followed by an overview of the key elements that you need to cover within each section. We’ve also included links to free resources to help you understand how to write each section.

The cleanly formatted Google Doc can be downloaded as a fully editable MS Word Document (DOCX format), so you can use it as-is or convert it to LaTeX.

FAQs: Research Paper Template

What format is the template (doc, pdf, ppt, etc.).

The research paper template is provided as a Google Doc. You can download it in MS Word format or make a copy to your Google Drive. You’re also welcome to convert it to whatever format works best for you, such as LaTeX or PDF.

What types of research papers can this template be used for?

The template follows the standard best-practice structure for formal academic research papers, so it is suitable for the vast majority of degrees, particularly those within the sciences.

Some universities may have some additional requirements, but these are typically minor, with the core structure remaining the same. Therefore, it’s always a good idea to double-check your university’s requirements before you finalise your structure.

Is this template for an undergrad, Masters or PhD-level research paper?

This template can be used for a research paper at any level of study. It may be slight overkill for an undergraduate-level study, but it certainly won’t be missing anything.

How long should my research paper be?

This depends entirely on your university’s specific requirements, so it’s best to check with them. We include generic word count ranges for each section within the template, but these are purely indicative.

What about the research proposal?

If you’re still working on your research proposal, we’ve got a template for that here .

We’ve also got loads of proposal-related guides and videos over on the Grad Coach blog .

How do I write a literature review?

We have a wealth of free resources on the Grad Coach Blog that unpack how to write a literature review from scratch. You can check out the literature review section of the blog here.

How do I create a research methodology?

We have a wealth of free resources on the Grad Coach Blog that unpack research methodology, both qualitative and quantitative. You can check out the methodology section of the blog here.

Can I share this research paper template with my friends/colleagues?

Yes, you’re welcome to share this template. If you want to post about it on your blog or social media, all we ask is that you reference this page as your source.

Can Grad Coach help me with my research paper?

Within the template, you’ll find plain-language explanations of each section, which should give you a fair amount of guidance. However, you’re also welcome to consider our private coaching services .

Want to create or adapt books like this? Learn more about how Pressbooks supports open publishing practices.

13.1 Formatting a Research Paper

Learning objectives.

Identify the major components of a research paper written using American Psychological Association (APA) style.
Apply general APA style and formatting conventions in a research paper.

In this chapter, you will learn how to use APA style , the documentation and formatting style followed by the American Psychological Association, as well as MLA style , from the Modern Language Association. There are a few major formatting styles used in academic texts, including AMA, Chicago, and Turabian:

AMA (American Medical Association) for medicine, health, and biological sciences
APA (American Psychological Association) for education, psychology, and the social sciences
Chicago—a common style used in everyday publications like magazines, newspapers, and books
MLA (Modern Language Association) for English, literature, arts, and humanities
Turabian—another common style designed for its universal application across all subjects and disciplines

While all the formatting and citation styles have their own use and applications, in this chapter we focus our attention on the two styles you are most likely to use in your academic studies: APA and MLA.

If you find that the rules of proper source documentation are difficult to keep straight, you are not alone. Writing a good research paper is, in and of itself, a major intellectual challenge. Having to follow detailed citation and formatting guidelines as well may seem like just one more task to add to an already-too-long list of requirements.

Following these guidelines, however, serves several important purposes. First, it signals to your readers that your paper should be taken seriously as a student’s contribution to a given academic or professional field; it is the literary equivalent of wearing a tailored suit to a job interview. Second, it shows that you respect other people’s work enough to give them proper credit for it. Finally, it helps your reader find additional materials if he or she wishes to learn more about your topic.

Furthermore, producing a letter-perfect APA-style paper need not be burdensome. Yes, it requires careful attention to detail. However, you can simplify the process if you keep these broad guidelines in mind:

Work ahead whenever you can. Chapter 11 “Writing from Research: What Will I Learn?” includes tips for keeping track of your sources early in the research process, which will save time later on.
Get it right the first time. Apply APA guidelines as you write, so you will not have much to correct during the editing stage. Again, putting in a little extra time early on can save time later.
Use the resources available to you. In addition to the guidelines provided in this chapter, you may wish to consult the APA website at http://www.apa.org or the Purdue University Online Writing lab at http://owl.english.purdue.edu , which regularly updates its online style guidelines.

General Formatting Guidelines

This chapter provides detailed guidelines for using the citation and formatting conventions developed by the American Psychological Association, or APA. Writers in disciplines as diverse as astrophysics, biology, psychology, and education follow APA style. The major components of a paper written in APA style are listed in the following box.

These are the major components of an APA-style paper:

Body, which includes the following:

Headings and, if necessary, subheadings to organize the content
In-text citations of research sources
References page

All these components must be saved in one document, not as separate documents.

The title page of your paper includes the following information:

Title of the paper
Author’s name
Name of the institution with which the author is affiliated
Header at the top of the page with the paper title (in capital letters) and the page number (If the title is lengthy, you may use a shortened form of it in the header.)

List the first three elements in the order given in the previous list, centered about one third of the way down from the top of the page. Use the headers and footers tool of your word-processing program to add the header, with the title text at the left and the page number in the upper-right corner. Your title page should look like the following example.

Beyond the Hype: Evaluating Low-Carb Diets cover page

The next page of your paper provides an abstract , or brief summary of your findings. An abstract does not need to be provided in every paper, but an abstract should be used in papers that include a hypothesis. A good abstract is concise—about one hundred fifty to two hundred fifty words—and is written in an objective, impersonal style. Your writing voice will not be as apparent here as in the body of your paper. When writing the abstract, take a just-the-facts approach, and summarize your research question and your findings in a few sentences.

In Chapter 12 “Writing a Research Paper” , you read a paper written by a student named Jorge, who researched the effectiveness of low-carbohydrate diets. Read Jorge’s abstract. Note how it sums up the major ideas in his paper without going into excessive detail.

Write an abstract summarizing your paper. Briefly introduce the topic, state your findings, and sum up what conclusions you can draw from your research. Use the word count feature of your word-processing program to make sure your abstract does not exceed one hundred fifty words.

Depending on your field of study, you may sometimes write research papers that present extensive primary research, such as your own experiment or survey. In your abstract, summarize your research question and your findings, and briefly indicate how your study relates to prior research in the field.

Margins, Pagination, and Headings

APA style requirements also address specific formatting concerns, such as margins, pagination, and heading styles, within the body of the paper. Review the following APA guidelines.

Use these general guidelines to format the paper:

Set the top, bottom, and side margins of your paper at 1 inch.
Use double-spaced text throughout your paper.
Use a standard font, such as Times New Roman or Arial, in a legible size (10- to 12-point).
Use continuous pagination throughout the paper, including the title page and the references section. Page numbers appear flush right within your header.
Section headings and subsection headings within the body of your paper use different types of formatting depending on the level of information you are presenting. Additional details from Jorge’s paper are provided.

Begin formatting the final draft of your paper according to APA guidelines. You may work with an existing document or set up a new document if you choose. Include the following:

Your title page
The abstract you created in Note 13.8 “Exercise 1”
Correct headers and page numbers for your title page and abstract

APA style uses section headings to organize information, making it easy for the reader to follow the writer’s train of thought and to know immediately what major topics are covered. Depending on the length and complexity of the paper, its major sections may also be divided into subsections, sub-subsections, and so on. These smaller sections, in turn, use different heading styles to indicate different levels of information. In essence, you are using headings to create a hierarchy of information.

The following heading styles used in APA formatting are listed in order of greatest to least importance:

Section headings use centered, boldface type. Headings use title case, with important words in the heading capitalized.
Subsection headings use left-aligned, boldface type. Headings use title case.
The third level uses left-aligned, indented, boldface type. Headings use a capital letter only for the first word, and they end in a period.
The fourth level follows the same style used for the previous level, but the headings are boldfaced and italicized.
The fifth level follows the same style used for the previous level, but the headings are italicized and not boldfaced.

Visually, the hierarchy of information is organized as indicated in Table 13.1 “Section Headings” .

Table 13.1 Section Headings

A college research paper may not use all the heading levels shown in Table 13.1 “Section Headings” , but you are likely to encounter them in academic journal articles that use APA style. For a brief paper, you may find that level 1 headings suffice. Longer or more complex papers may need level 2 headings or other lower-level headings to organize information clearly. Use your outline to craft your major section headings and determine whether any subtopics are substantial enough to require additional levels of headings.

Working with the document you developed in Note 13.11 “Exercise 2” , begin setting up the heading structure of the final draft of your research paper according to APA guidelines. Include your title and at least two to three major section headings, and follow the formatting guidelines provided above. If your major sections should be broken into subsections, add those headings as well. Use your outline to help you.

Because Jorge used only level 1 headings, his Exercise 3 would look like the following:

Citation Guidelines

In-text citations.

Throughout the body of your paper, include a citation whenever you quote or paraphrase material from your research sources. As you learned in Chapter 11 “Writing from Research: What Will I Learn?” , the purpose of citations is twofold: to give credit to others for their ideas and to allow your reader to follow up and learn more about the topic if desired. Your in-text citations provide basic information about your source; each source you cite will have a longer entry in the references section that provides more detailed information.

In-text citations must provide the name of the author or authors and the year the source was published. (When a given source does not list an individual author, you may provide the source title or the name of the organization that published the material instead.) When directly quoting a source, it is also required that you include the page number where the quote appears in your citation.

This information may be included within the sentence or in a parenthetical reference at the end of the sentence, as in these examples.

Epstein (2010) points out that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (p. 137).

Here, the writer names the source author when introducing the quote and provides the publication date in parentheses after the author’s name. The page number appears in parentheses after the closing quotation marks and before the period that ends the sentence.

Addiction researchers caution that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (Epstein, 2010, p. 137).

Here, the writer provides a parenthetical citation at the end of the sentence that includes the author’s name, the year of publication, and the page number separated by commas. Again, the parenthetical citation is placed after the closing quotation marks and before the period at the end of the sentence.

As noted in the book Junk Food, Junk Science (Epstein, 2010, p. 137), “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive.”

Here, the writer chose to mention the source title in the sentence (an optional piece of information to include) and followed the title with a parenthetical citation. Note that the parenthetical citation is placed before the comma that signals the end of the introductory phrase.

David Epstein’s book Junk Food, Junk Science (2010) pointed out that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (p. 137).

Another variation is to introduce the author and the source title in your sentence and include the publication date and page number in parentheses within the sentence or at the end of the sentence. As long as you have included the essential information, you can choose the option that works best for that particular sentence and source.

Citing a book with a single author is usually a straightforward task. Of course, your research may require that you cite many other types of sources, such as books or articles with more than one author or sources with no individual author listed. You may also need to cite sources available in both print and online and nonprint sources, such as websites and personal interviews. Chapter 13 “APA and MLA Documentation and Formatting” , Section 13.2 “Citing and Referencing Techniques” and Section 13.3 “Creating a References Section” provide extensive guidelines for citing a variety of source types.

Writing at Work

APA is just one of several different styles with its own guidelines for documentation, formatting, and language usage. Depending on your field of interest, you may be exposed to additional styles, such as the following:

MLA style. Determined by the Modern Languages Association and used for papers in literature, languages, and other disciplines in the humanities.
Chicago style. Outlined in the Chicago Manual of Style and sometimes used for papers in the humanities and the sciences; many professional organizations use this style for publications as well.
Associated Press (AP) style. Used by professional journalists.

References List

The brief citations included in the body of your paper correspond to the more detailed citations provided at the end of the paper in the references section. In-text citations provide basic information—the author’s name, the publication date, and the page number if necessary—while the references section provides more extensive bibliographical information. Again, this information allows your reader to follow up on the sources you cited and do additional reading about the topic if desired.

The specific format of entries in the list of references varies slightly for different source types, but the entries generally include the following information:

The name(s) of the author(s) or institution that wrote the source
The year of publication and, where applicable, the exact date of publication
The full title of the source
For books, the city of publication
For articles or essays, the name of the periodical or book in which the article or essay appears
For magazine and journal articles, the volume number, issue number, and pages where the article appears
For sources on the web, the URL where the source is located

The references page is double spaced and lists entries in alphabetical order by the author’s last name. If an entry continues for more than one line, the second line and each subsequent line are indented five spaces. Review the following example. ( Chapter 13 “APA and MLA Documentation and Formatting” , Section 13.3 “Creating a References Section” provides extensive guidelines for formatting reference entries for different types of sources.)

In APA style, book and article titles are formatted in sentence case, not title case. Sentence case means that only the first word is capitalized, along with any proper nouns.

Key Takeaways

Following proper citation and formatting guidelines helps writers ensure that their work will be taken seriously, give proper credit to other authors for their work, and provide valuable information to readers.
Working ahead and taking care to cite sources correctly the first time are ways writers can save time during the editing stage of writing a research paper.
APA papers usually include an abstract that concisely summarizes the paper.
APA papers use a specific headings structure to provide a clear hierarchy of information.
In APA papers, in-text citations usually include the name(s) of the author(s) and the year of publication.
In-text citations correspond to entries in the references section, which provide detailed bibliographical information about a source.

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Practical Research chapter 1 2 and 3

In the software industry, "Gadget" refers to computer programs that provide services without needing an independent application to be launched for each one, but instead run in an environment that manages multiple gadgets. There are several implementations based on existing software development techniques, like JavaScript, form input, and various image formats.

Related Papers

Saul Greenberg

ABSTRACT Physical widgets, or phidgets, comprise devices and software that are almost direct analogs of graphical user interface widgets. Like widgets, phidgets abstract and package input and output devices: they hide implementation and construction details while exposing functionality through a well-defined API. They also have an (optional) on-screen interface.

Aptisi Transactions On Technopreneurship (ATT)

Aptisi Transactions on Technopreneurship Journal

The gadget is a sophisticated item that can present a variety of news media, social networking, hobbies, and even entertainment. The presence of gadgets today makes some people become dependent. If the gadget is damaged, they will repair the gadget itself or bring it to the service place. The problem in this study is the difficulty of finding information about the place of seller of gadget components and looking for a trusted service place, the nearest location and affordable prices. To overcome this problem, the author designed an application called Gadgetku.Id used a qualitative research method consisting of data collection, data analysis and system design. In this application have 2 main services, namely service and shop. The purpose of designing this application is to be able to assist users in finding a trusted service place, the nearest location, safe, scheduled and without the need to go to the service place and help to find gadget needs through the shop feature.

Abstract Physical widgets or phidgets are to physical user interfaces what widgets are to graphical user interfaces. Similar to widgets, phidgets abstract and package input and output devices: they hide implementation and construction details, they expose functionality through a well-defined API, and they have an (optional) on-screen interactive interface for displaying and controlling device state.

Srikanth Jatla

Here in this paper we proposed a virtual class environment by applying off the shelf cot integration methodologies in a traditional classroom, the model we proposed helps to remove the boundaries between tele-education and physical classroom activities in terms of the teacher's experience and seamlessly integrates these two currently separate educational practices. More specifically, we replace the legacy desktop based tele education system. Hence the teachers are not opting to mouse and keyboards than marker and whiteboard. In the proposed model, teachers can use multiple traditional approaches while interacting with students who are available on virtual class. Now a days, rather than physical class room education, craze and necessity for distance education is under rapid growth. The time of the students is better handled in this type because they can even have lessons from teachers of other nations and saves their travelling time. This helps them to study working for their liv...

sigit widiyanto

Widget is kind of application that provides a single service such as a map, news feed, simple clock, and battery-life indicators. It is developed to facilitate user interface (UI) design. A user interface function may be implemented using different widgets developed on different UI platforms. This article presents a comprehensive review on Java Swing as a platform to develop widgets. It is a platform that is generally used in various applications, such as in desktop, web browser, and mobile phone. Furthermore, we also describe UI elements of Java Swing’s components used to establish widgets. At the end, this article discusses comparison between Java Swing and several commonly used UI platforms.

Tanguy Wettengel , Dinh Quang

—Widget selection when designing user interfaces is a rather intuitive task. No clearly established methodology containing in-depth descriptions of widgets or explicit rules to choose them has been included in the major development processes. Widget catalogs are only partially specified and do not overtly consider the domain-field knowledge representation as bound to current tasks. Moreover, these representations have not undergone any systematic approach from the point of view of their structure. The first aim of this paper is to formally describe the major types of content that widgets can host from this perspective. We call these types " Information Structures " and divide them into 5 categories (" atom " , " collection " , " hierarchy " , " taxonomy " and " network "). We then specify a series of features allowing to classify widgets alongside with their informational content structure and set a framework for widget description.

9th IFAC Symposium Advances in Control Education

Denis Gillet

Many ubiquitous computing environments rely on special purpose physical devices to for input (sensors, etc.) and output (motors, lights, etc.) Yet everyday programmers interested in such environments face considerable hurdles creating, developing and combining physical devices and interfacing them to conventional programming languages.

Proceedings of the third annual ACM conference on Hypertext - HYPERTEXT '91

Brian Beckman

Timothy C Lethbridge

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Chapter 1. Introduction

“Science is in danger, and for that reason it is becoming dangerous” -Pierre Bourdieu, Science of Science and Reflexivity

Why an Open Access Textbook on Qualitative Research Methods?

I have been teaching qualitative research methods to both undergraduates and graduate students for many years. Although there are some excellent textbooks out there, they are often costly, and none of them, to my mind, properly introduces qualitative research methods to the beginning student (whether undergraduate or graduate student). In contrast, this open-access textbook is designed as a (free) true introduction to the subject, with helpful, practical pointers on how to conduct research and how to access more advanced instruction.

Textbooks are typically arranged in one of two ways: (1) by technique (each chapter covers one method used in qualitative research); or (2) by process (chapters advance from research design through publication). But both of these approaches are necessary for the beginner student. This textbook will have sections dedicated to the process as well as the techniques of qualitative research. This is a true “comprehensive” book for the beginning student. In addition to covering techniques of data collection and data analysis, it provides a road map of how to get started and how to keep going and where to go for advanced instruction. It covers aspects of research design and research communication as well as methods employed. Along the way, it includes examples from many different disciplines in the social sciences.

The primary goal has been to create a useful, accessible, engaging textbook for use across many disciplines. And, let’s face it. Textbooks can be boring. I hope readers find this to be a little different. I have tried to write in a practical and forthright manner, with many lively examples and references to good and intellectually creative qualitative research. Woven throughout the text are short textual asides (in colored textboxes) by professional (academic) qualitative researchers in various disciplines. These short accounts by practitioners should help inspire students. So, let’s begin!

What is Research?

When we use the word research , what exactly do we mean by that? This is one of those words that everyone thinks they understand, but it is worth beginning this textbook with a short explanation. We use the term to refer to “empirical research,” which is actually a historically specific approach to understanding the world around us. Think about how you know things about the world. [1] You might know your mother loves you because she’s told you she does. Or because that is what “mothers” do by tradition. Or you might know because you’ve looked for evidence that she does, like taking care of you when you are sick or reading to you in bed or working two jobs so you can have the things you need to do OK in life. Maybe it seems churlish to look for evidence; you just take it “on faith” that you are loved.

Only one of the above comes close to what we mean by research. Empirical research is research (investigation) based on evidence. Conclusions can then be drawn from observable data. This observable data can also be “tested” or checked. If the data cannot be tested, that is a good indication that we are not doing research. Note that we can never “prove” conclusively, through observable data, that our mothers love us. We might have some “disconfirming evidence” (that time she didn’t show up to your graduation, for example) that could push you to question an original hypothesis , but no amount of “confirming evidence” will ever allow us to say with 100% certainty, “my mother loves me.” Faith and tradition and authority work differently. Our knowledge can be 100% certain using each of those alternative methods of knowledge, but our certainty in those cases will not be based on facts or evidence.

For many periods of history, those in power have been nervous about “science” because it uses evidence and facts as the primary source of understanding the world, and facts can be at odds with what power or authority or tradition want you to believe. That is why I say that scientific empirical research is a historically specific approach to understand the world. You are in college or university now partly to learn how to engage in this historically specific approach.

In the sixteenth and seventeenth centuries in Europe, there was a newfound respect for empirical research, some of which was seriously challenging to the established church. Using observations and testing them, scientists found that the earth was not at the center of the universe, for example, but rather that it was but one planet of many which circled the sun. [2] For the next two centuries, the science of astronomy, physics, biology, and chemistry emerged and became disciplines taught in universities. All used the scientific method of observation and testing to advance knowledge. Knowledge about people , however, and social institutions, however, was still left to faith, tradition, and authority. Historians and philosophers and poets wrote about the human condition, but none of them used research to do so. [3]

It was not until the nineteenth century that “social science” really emerged, using the scientific method (empirical observation) to understand people and social institutions. New fields of sociology, economics, political science, and anthropology emerged. The first sociologists, people like Auguste Comte and Karl Marx, sought specifically to apply the scientific method of research to understand society, Engels famously claiming that Marx had done for the social world what Darwin did for the natural world, tracings its laws of development. Today we tend to take for granted the naturalness of science here, but it is actually a pretty recent and radical development.

To return to the question, “does your mother love you?” Well, this is actually not really how a researcher would frame the question, as it is too specific to your case. It doesn’t tell us much about the world at large, even if it does tell us something about you and your relationship with your mother. A social science researcher might ask, “do mothers love their children?” Or maybe they would be more interested in how this loving relationship might change over time (e.g., “do mothers love their children more now than they did in the 18th century when so many children died before reaching adulthood?”) or perhaps they might be interested in measuring quality of love across cultures or time periods, or even establishing “what love looks like” using the mother/child relationship as a site of exploration. All of these make good research questions because we can use observable data to answer them.

What is Qualitative Research?

“All we know is how to learn. How to study, how to listen, how to talk, how to tell. If we don’t tell the world, we don’t know the world. We’re lost in it, we die.” -Ursula LeGuin, The Telling

At its simplest, qualitative research is research about the social world that does not use numbers in its analyses. All those who fear statistics can breathe a sigh of relief – there are no mathematical formulae or regression models in this book! But this definition is less about what qualitative research can be and more about what it is not. To be honest, any simple statement will fail to capture the power and depth of qualitative research. One way of contrasting qualitative research to quantitative research is to note that the focus of qualitative research is less about explaining and predicting relationships between variables and more about understanding the social world. To use our mother love example, the question about “what love looks like” is a good question for the qualitative researcher while all questions measuring love or comparing incidences of love (both of which require measurement) are good questions for quantitative researchers. Patton writes,

Qualitative data describe. They take us, as readers, into the time and place of the observation so that we know what it was like to have been there. They capture and communicate someone else’s experience of the world in his or her own words. Qualitative data tell a story. ( Patton 2002:47 )

Qualitative researchers are asking different questions about the world than their quantitative colleagues. Even when researchers are employed in “mixed methods” research ( both quantitative and qualitative), they are using different methods to address different questions of the study. I do a lot of research about first-generation and working-college college students. Where a quantitative researcher might ask, how many first-generation college students graduate from college within four years? Or does first-generation college status predict high student debt loads? A qualitative researcher might ask, how does the college experience differ for first-generation college students? What is it like to carry a lot of debt, and how does this impact the ability to complete college on time? Both sets of questions are important, but they can only be answered using specific tools tailored to those questions. For the former, you need large numbers to make adequate comparisons. For the latter, you need to talk to people, find out what they are thinking and feeling, and try to inhabit their shoes for a little while so you can make sense of their experiences and beliefs.

Examples of Qualitative Research

You have probably seen examples of qualitative research before, but you might not have paid particular attention to how they were produced or realized that the accounts you were reading were the result of hours, months, even years of research “in the field.” A good qualitative researcher will present the product of their hours of work in such a way that it seems natural, even obvious, to the reader. Because we are trying to convey what it is like answers, qualitative research is often presented as stories – stories about how people live their lives, go to work, raise their children, interact with one another. In some ways, this can seem like reading particularly insightful novels. But, unlike novels, there are very specific rules and guidelines that qualitative researchers follow to ensure that the “story” they are telling is accurate , a truthful rendition of what life is like for the people being studied. Most of this textbook will be spent conveying those rules and guidelines. Let’s take a look, first, however, at three examples of what the end product looks like. I have chosen these three examples to showcase very different approaches to qualitative research, and I will return to these five examples throughout the book. They were all published as whole books (not chapters or articles), and they are worth the long read, if you have the time. I will also provide some information on how these books came to be and the length of time it takes to get them into book version. It is important you know about this process, and the rest of this textbook will help explain why it takes so long to conduct good qualitative research!

Example 1 : The End Game (ethnography + interviews)

Corey Abramson is a sociologist who teaches at the University of Arizona. In 2015 he published The End Game: How Inequality Shapes our Final Years ( 2015 ). This book was based on the research he did for his dissertation at the University of California-Berkeley in 2012. Actually, the dissertation was completed in 2012 but the work that was produced that took several years. The dissertation was entitled, “This is How We Live, This is How We Die: Social Stratification, Aging, and Health in Urban America” ( 2012 ). You can see how the book version, which was written for a more general audience, has a more engaging sound to it, but that the dissertation version, which is what academic faculty read and evaluate, has a more descriptive title. You can read the title and know that this is a study about aging and health and that the focus is going to be inequality and that the context (place) is going to be “urban America.” It’s a study about “how” people do something – in this case, how they deal with aging and death. This is the very first sentence of the dissertation, “From our first breath in the hospital to the day we die, we live in a society characterized by unequal opportunities for maintaining health and taking care of ourselves when ill. These disparities reflect persistent racial, socio-economic, and gender-based inequalities and contribute to their persistence over time” ( 1 ). What follows is a truthful account of how that is so.

Cory Abramson spent three years conducting his research in four different urban neighborhoods. We call the type of research he conducted “comparative ethnographic” because he designed his study to compare groups of seniors as they went about their everyday business. It’s comparative because he is comparing different groups (based on race, class, gender) and ethnographic because he is studying the culture/way of life of a group. [4] He had an educated guess, rooted in what previous research had shown and what social theory would suggest, that people’s experiences of aging differ by race, class, and gender. So, he set up a research design that would allow him to observe differences. He chose two primarily middle-class (one was racially diverse and the other was predominantly White) and two primarily poor neighborhoods (one was racially diverse and the other was predominantly African American). He hung out in senior centers and other places seniors congregated, watched them as they took the bus to get prescriptions filled, sat in doctor’s offices with them, and listened to their conversations with each other. He also conducted more formal conversations, what we call in-depth interviews, with sixty seniors from each of the four neighborhoods. As with a lot of fieldwork , as he got closer to the people involved, he both expanded and deepened his reach –

By the end of the project, I expanded my pool of general observations to include various settings frequented by seniors: apartment building common rooms, doctors’ offices, emergency rooms, pharmacies, senior centers, bars, parks, corner stores, shopping centers, pool halls, hair salons, coffee shops, and discount stores. Over the course of the three years of fieldwork, I observed hundreds of elders, and developed close relationships with a number of them. ( 2012:10 )

When Abramson rewrote the dissertation for a general audience and published his book in 2015, it got a lot of attention. It is a beautifully written book and it provided insight into a common human experience that we surprisingly know very little about. It won the Outstanding Publication Award by the American Sociological Association Section on Aging and the Life Course and was featured in the New York Times . The book was about aging, and specifically how inequality shapes the aging process, but it was also about much more than that. It helped show how inequality affects people’s everyday lives. For example, by observing the difficulties the poor had in setting up appointments and getting to them using public transportation and then being made to wait to see a doctor, sometimes in standing-room-only situations, when they are unwell, and then being treated dismissively by hospital staff, Abramson allowed readers to feel the material reality of being poor in the US. Comparing these examples with seniors with adequate supplemental insurance who have the resources to hire car services or have others assist them in arranging care when they need it, jolts the reader to understand and appreciate the difference money makes in the lives and circumstances of us all, and in a way that is different than simply reading a statistic (“80% of the poor do not keep regular doctor’s appointments”) does. Qualitative research can reach into spaces and places that often go unexamined and then reports back to the rest of us what it is like in those spaces and places.

Example 2: Racing for Innocence (Interviews + Content Analysis + Fictional Stories)

Jennifer Pierce is a Professor of American Studies at the University of Minnesota. Trained as a sociologist, she has written a number of books about gender, race, and power. Her very first book, Gender Trials: Emotional Lives in Contemporary Law Firms, published in 1995, is a brilliant look at gender dynamics within two law firms. Pierce was a participant observer, working as a paralegal, and she observed how female lawyers and female paralegals struggled to obtain parity with their male colleagues.

Fifteen years later, she reexamined the context of the law firm to include an examination of racial dynamics, particularly how elite white men working in these spaces created and maintained a culture that made it difficult for both female attorneys and attorneys of color to thrive. Her book, Racing for Innocence: Whiteness, Gender, and the Backlash Against Affirmative Action , published in 2012, is an interesting and creative blending of interviews with attorneys, content analyses of popular films during this period, and fictional accounts of racial discrimination and sexual harassment. The law firm she chose to study had come under an affirmative action order and was in the process of implementing equitable policies and programs. She wanted to understand how recipients of white privilege (the elite white male attorneys) come to deny the role they play in reproducing inequality. Through interviews with attorneys who were present both before and during the affirmative action order, she creates a historical record of the “bad behavior” that necessitated new policies and procedures, but also, and more importantly , probed the participants ’ understanding of this behavior. It should come as no surprise that most (but not all) of the white male attorneys saw little need for change, and that almost everyone else had accounts that were different if not sometimes downright harrowing.

I’ve used Pierce’s book in my qualitative research methods courses as an example of an interesting blend of techniques and presentation styles. My students often have a very difficult time with the fictional accounts she includes. But they serve an important communicative purpose here. They are her attempts at presenting “both sides” to an objective reality – something happens (Pierce writes this something so it is very clear what it is), and the two participants to the thing that happened have very different understandings of what this means. By including these stories, Pierce presents one of her key findings – people remember things differently and these different memories tend to support their own ideological positions. I wonder what Pierce would have written had she studied the murder of George Floyd or the storming of the US Capitol on January 6 or any number of other historic events whose observers and participants record very different happenings.

This is not to say that qualitative researchers write fictional accounts. In fact, the use of fiction in our work remains controversial. When used, it must be clearly identified as a presentation device, as Pierce did. I include Racing for Innocence here as an example of the multiple uses of methods and techniques and the way that these work together to produce better understandings by us, the readers, of what Pierce studied. We readers come away with a better grasp of how and why advantaged people understate their own involvement in situations and structures that advantage them. This is normal human behavior , in other words. This case may have been about elite white men in law firms, but the general insights here can be transposed to other settings. Indeed, Pierce argues that more research needs to be done about the role elites play in the reproduction of inequality in the workplace in general.

Example 3: Amplified Advantage (Mixed Methods: Survey Interviews + Focus Groups + Archives)

The final example comes from my own work with college students, particularly the ways in which class background affects the experience of college and outcomes for graduates. I include it here as an example of mixed methods, and for the use of supplementary archival research. I’ve done a lot of research over the years on first-generation, low-income, and working-class college students. I am curious (and skeptical) about the possibility of social mobility today, particularly with the rising cost of college and growing inequality in general. As one of the few people in my family to go to college, I didn’t grow up with a lot of examples of what college was like or how to make the most of it. And when I entered graduate school, I realized with dismay that there were very few people like me there. I worried about becoming too different from my family and friends back home. And I wasn’t at all sure that I would ever be able to pay back the huge load of debt I was taking on. And so I wrote my dissertation and first two books about working-class college students. These books focused on experiences in college and the difficulties of navigating between family and school ( Hurst 2010a, 2012 ). But even after all that research, I kept coming back to wondering if working-class students who made it through college had an equal chance at finding good jobs and happy lives,

What happens to students after college? Do working-class students fare as well as their peers? I knew from my own experience that barriers continued through graduate school and beyond, and that my debtload was higher than that of my peers, constraining some of the choices I made when I graduated. To answer these questions, I designed a study of students attending small liberal arts colleges, the type of college that tried to equalize the experience of students by requiring all students to live on campus and offering small classes with lots of interaction with faculty. These private colleges tend to have more money and resources so they can provide financial aid to low-income students. They also attract some very wealthy students. Because they enroll students across the class spectrum, I would be able to draw comparisons. I ended up spending about four years collecting data, both a survey of more than 2000 students (which formed the basis for quantitative analyses) and qualitative data collection (interviews, focus groups, archival research, and participant observation). This is what we call a “mixed methods” approach because we use both quantitative and qualitative data. The survey gave me a large enough number of students that I could make comparisons of the how many kind, and to be able to say with some authority that there were in fact significant differences in experience and outcome by class (e.g., wealthier students earned more money and had little debt; working-class students often found jobs that were not in their chosen careers and were very affected by debt, upper-middle-class students were more likely to go to graduate school). But the survey analyses could not explain why these differences existed. For that, I needed to talk to people and ask them about their motivations and aspirations. I needed to understand their perceptions of the world, and it is very hard to do this through a survey.

By interviewing students and recent graduates, I was able to discern particular patterns and pathways through college and beyond. Specifically, I identified three versions of gameplay. Upper-middle-class students, whose parents were themselves professionals (academics, lawyers, managers of non-profits), saw college as the first stage of their education and took classes and declared majors that would prepare them for graduate school. They also spent a lot of time building their resumes, taking advantage of opportunities to help professors with their research, or study abroad. This helped them gain admission to highly-ranked graduate schools and interesting jobs in the public sector. In contrast, upper-class students, whose parents were wealthy and more likely to be engaged in business (as CEOs or other high-level directors), prioritized building social capital. They did this by joining fraternities and sororities and playing club sports. This helped them when they graduated as they called on friends and parents of friends to find them well-paying jobs. Finally, low-income, first-generation, and working-class students were often adrift. They took the classes that were recommended to them but without the knowledge of how to connect them to life beyond college. They spent time working and studying rather than partying or building their resumes. All three sets of students thought they were “doing college” the right way, the way that one was supposed to do college. But these three versions of gameplay led to distinct outcomes that advantaged some students over others. I titled my work “Amplified Advantage” to highlight this process.

These three examples, Cory Abramson’s The End Game , Jennifer Peirce’s Racing for Innocence, and my own Amplified Advantage, demonstrate the range of approaches and tools available to the qualitative researcher. They also help explain why qualitative research is so important. Numbers can tell us some things about the world, but they cannot get at the hearts and minds, motivations and beliefs of the people who make up the social worlds we inhabit. For that, we need tools that allow us to listen and make sense of what people tell us and show us. That is what good qualitative research offers us.

How Is This Book Organized?

This textbook is organized as a comprehensive introduction to the use of qualitative research methods. The first half covers general topics (e.g., approaches to qualitative research, ethics) and research design (necessary steps for building a successful qualitative research study). The second half reviews various data collection and data analysis techniques. Of course, building a successful qualitative research study requires some knowledge of data collection and data analysis so the chapters in the first half and the chapters in the second half should be read in conversation with each other. That said, each chapter can be read on its own for assistance with a particular narrow topic. In addition to the chapters, a helpful glossary can be found in the back of the book. Rummage around in the text as needed.

Chapter Descriptions

Chapter 2 provides an overview of the Research Design Process. How does one begin a study? What is an appropriate research question? How is the study to be done – with what methods ? Involving what people and sites? Although qualitative research studies can and often do change and develop over the course of data collection, it is important to have a good idea of what the aims and goals of your study are at the outset and a good plan of how to achieve those aims and goals. Chapter 2 provides a road map of the process.

Chapter 3 describes and explains various ways of knowing the (social) world. What is it possible for us to know about how other people think or why they behave the way they do? What does it mean to say something is a “fact” or that it is “well-known” and understood? Qualitative researchers are particularly interested in these questions because of the types of research questions we are interested in answering (the how questions rather than the how many questions of quantitative research). Qualitative researchers have adopted various epistemological approaches. Chapter 3 will explore these approaches, highlighting interpretivist approaches that acknowledge the subjective aspect of reality – in other words, reality and knowledge are not objective but rather influenced by (interpreted through) people.

Chapter 4 focuses on the practical matter of developing a research question and finding the right approach to data collection. In any given study (think of Cory Abramson’s study of aging, for example), there may be years of collected data, thousands of observations , hundreds of pages of notes to read and review and make sense of. If all you had was a general interest area (“aging”), it would be very difficult, nearly impossible, to make sense of all of that data. The research question provides a helpful lens to refine and clarify (and simplify) everything you find and collect. For that reason, it is important to pull out that lens (articulate the research question) before you get started. In the case of the aging study, Cory Abramson was interested in how inequalities affected understandings and responses to aging. It is for this reason he designed a study that would allow him to compare different groups of seniors (some middle-class, some poor). Inevitably, he saw much more in the three years in the field than what made it into his book (or dissertation), but he was able to narrow down the complexity of the social world to provide us with this rich account linked to the original research question. Developing a good research question is thus crucial to effective design and a successful outcome. Chapter 4 will provide pointers on how to do this. Chapter 4 also provides an overview of general approaches taken to doing qualitative research and various “traditions of inquiry.”

Chapter 5 explores sampling . After you have developed a research question and have a general idea of how you will collect data (Observations? Interviews?), how do you go about actually finding people and sites to study? Although there is no “correct number” of people to interview , the sample should follow the research question and research design. Unlike quantitative research, qualitative research involves nonprobability sampling. Chapter 5 explains why this is so and what qualities instead make a good sample for qualitative research.

Chapter 6 addresses the importance of reflexivity in qualitative research. Related to epistemological issues of how we know anything about the social world, qualitative researchers understand that we the researchers can never be truly neutral or outside the study we are conducting. As observers, we see things that make sense to us and may entirely miss what is either too obvious to note or too different to comprehend. As interviewers, as much as we would like to ask questions neutrally and remain in the background, interviews are a form of conversation, and the persons we interview are responding to us . Therefore, it is important to reflect upon our social positions and the knowledges and expectations we bring to our work and to work through any blind spots that we may have. Chapter 6 provides some examples of reflexivity in practice and exercises for thinking through one’s own biases.

Chapter 7 is a very important chapter and should not be overlooked. As a practical matter, it should also be read closely with chapters 6 and 8. Because qualitative researchers deal with people and the social world, it is imperative they develop and adhere to a strong ethical code for conducting research in a way that does not harm. There are legal requirements and guidelines for doing so (see chapter 8), but these requirements should not be considered synonymous with the ethical code required of us. Each researcher must constantly interrogate every aspect of their research, from research question to design to sample through analysis and presentation, to ensure that a minimum of harm (ideally, zero harm) is caused. Because each research project is unique, the standards of care for each study are unique. Part of being a professional researcher is carrying this code in one’s heart, being constantly attentive to what is required under particular circumstances. Chapter 7 provides various research scenarios and asks readers to weigh in on the suitability and appropriateness of the research. If done in a class setting, it will become obvious fairly quickly that there are often no absolutely correct answers, as different people find different aspects of the scenarios of greatest importance. Minimizing the harm in one area may require possible harm in another. Being attentive to all the ethical aspects of one’s research and making the best judgments one can, clearly and consciously, is an integral part of being a good researcher.

Chapter 8 , best to be read in conjunction with chapter 7, explains the role and importance of Institutional Review Boards (IRBs) . Under federal guidelines, an IRB is an appropriately constituted group that has been formally designated to review and monitor research involving human subjects . Every institution that receives funding from the federal government has an IRB. IRBs have the authority to approve, require modifications to (to secure approval), or disapprove research. This group review serves an important role in the protection of the rights and welfare of human research subjects. Chapter 8 reviews the history of IRBs and the work they do but also argues that IRBs’ review of qualitative research is often both over-inclusive and under-inclusive. Some aspects of qualitative research are not well understood by IRBs, given that they were developed to prevent abuses in biomedical research. Thus, it is important not to rely on IRBs to identify all the potential ethical issues that emerge in our research (see chapter 7).

Chapter 9 provides help for getting started on formulating a research question based on gaps in the pre-existing literature. Research is conducted as part of a community, even if particular studies are done by single individuals (or small teams). What any of us finds and reports back becomes part of a much larger body of knowledge. Thus, it is important that we look at the larger body of knowledge before we actually start our bit to see how we can best contribute. When I first began interviewing working-class college students, there was only one other similar study I could find, and it hadn’t been published (it was a dissertation of students from poor backgrounds). But there had been a lot published by professors who had grown up working class and made it through college despite the odds. These accounts by “working-class academics” became an important inspiration for my study and helped me frame the questions I asked the students I interviewed. Chapter 9 will provide some pointers on how to search for relevant literature and how to use this to refine your research question.

Chapter 10 serves as a bridge between the two parts of the textbook, by introducing techniques of data collection. Qualitative research is often characterized by the form of data collection – for example, an ethnographic study is one that employs primarily observational data collection for the purpose of documenting and presenting a particular culture or ethnos. Techniques can be effectively combined, depending on the research question and the aims and goals of the study. Chapter 10 provides a general overview of all the various techniques and how they can be combined.

The second part of the textbook moves into the doing part of qualitative research once the research question has been articulated and the study designed. Chapters 11 through 17 cover various data collection techniques and approaches. Chapters 18 and 19 provide a very simple overview of basic data analysis. Chapter 20 covers communication of the data to various audiences, and in various formats.

Chapter 11 begins our overview of data collection techniques with a focus on interviewing , the true heart of qualitative research. This technique can serve as the primary and exclusive form of data collection, or it can be used to supplement other forms (observation, archival). An interview is distinct from a survey, where questions are asked in a specific order and often with a range of predetermined responses available. Interviews can be conversational and unstructured or, more conventionally, semistructured , where a general set of interview questions “guides” the conversation. Chapter 11 covers the basics of interviews: how to create interview guides, how many people to interview, where to conduct the interview, what to watch out for (how to prepare against things going wrong), and how to get the most out of your interviews.

Chapter 12 covers an important variant of interviewing, the focus group. Focus groups are semistructured interviews with a group of people moderated by a facilitator (the researcher or researcher’s assistant). Focus groups explicitly use group interaction to assist in the data collection. They are best used to collect data on a specific topic that is non-personal and shared among the group. For example, asking a group of college students about a common experience such as taking classes by remote delivery during the pandemic year of 2020. Chapter 12 covers the basics of focus groups: when to use them, how to create interview guides for them, and how to run them effectively.

Chapter 13 moves away from interviewing to the second major form of data collection unique to qualitative researchers – observation . Qualitative research that employs observation can best be understood as falling on a continuum of “fly on the wall” observation (e.g., observing how strangers interact in a doctor’s waiting room) to “participant” observation, where the researcher is also an active participant of the activity being observed. For example, an activist in the Black Lives Matter movement might want to study the movement, using her inside position to gain access to observe key meetings and interactions. Chapter 13 covers the basics of participant observation studies: advantages and disadvantages, gaining access, ethical concerns related to insider/outsider status and entanglement, and recording techniques.

Chapter 14 takes a closer look at “deep ethnography” – immersion in the field of a particularly long duration for the purpose of gaining a deeper understanding and appreciation of a particular culture or social world. Clifford Geertz called this “deep hanging out.” Whereas participant observation is often combined with semistructured interview techniques, deep ethnography’s commitment to “living the life” or experiencing the situation as it really is demands more conversational and natural interactions with people. These interactions and conversations may take place over months or even years. As can be expected, there are some costs to this technique, as well as some very large rewards when done competently. Chapter 14 provides some examples of deep ethnographies that will inspire some beginning researchers and intimidate others.

Chapter 15 moves in the opposite direction of deep ethnography, a technique that is the least positivist of all those discussed here, to mixed methods , a set of techniques that is arguably the most positivist . A mixed methods approach combines both qualitative data collection and quantitative data collection, commonly by combining a survey that is analyzed statistically (e.g., cross-tabs or regression analyses of large number probability samples) with semi-structured interviews. Although it is somewhat unconventional to discuss mixed methods in textbooks on qualitative research, I think it is important to recognize this often-employed approach here. There are several advantages and some disadvantages to taking this route. Chapter 16 will describe those advantages and disadvantages and provide some particular guidance on how to design a mixed methods study for maximum effectiveness.

Chapter 16 covers data collection that does not involve live human subjects at all – archival and historical research (chapter 17 will also cover data that does not involve interacting with human subjects). Sometimes people are unavailable to us, either because they do not wish to be interviewed or observed (as is the case with many “elites”) or because they are too far away, in both place and time. Fortunately, humans leave many traces and we can often answer questions we have by examining those traces. Special collections and archives can be goldmines for social science research. This chapter will explain how to access these places, for what purposes, and how to begin to make sense of what you find.

Chapter 17 covers another data collection area that does not involve face-to-face interaction with humans: content analysis . Although content analysis may be understood more properly as a data analysis technique, the term is often used for the entire approach, which will be the case here. Content analysis involves interpreting meaning from a body of text. This body of text might be something found in historical records (see chapter 16) or something collected by the researcher, as in the case of comment posts on a popular blog post. I once used the stories told by student loan debtors on the website studentloanjustice.org as the content I analyzed. Content analysis is particularly useful when attempting to define and understand prevalent stories or communication about a topic of interest. In other words, when we are less interested in what particular people (our defined sample) are doing or believing and more interested in what general narratives exist about a particular topic or issue. This chapter will explore different approaches to content analysis and provide helpful tips on how to collect data, how to turn that data into codes for analysis, and how to go about presenting what is found through analysis.

Where chapter 17 has pushed us towards data analysis, chapters 18 and 19 are all about what to do with the data collected, whether that data be in the form of interview transcripts or fieldnotes from observations. Chapter 18 introduces the basics of coding , the iterative process of assigning meaning to the data in order to both simplify and identify patterns. What is a code and how does it work? What are the different ways of coding data, and when should you use them? What is a codebook, and why do you need one? What does the process of data analysis look like?

Chapter 19 goes further into detail on codes and how to use them, particularly the later stages of coding in which our codes are refined, simplified, combined, and organized. These later rounds of coding are essential to getting the most out of the data we’ve collected. As students are often overwhelmed with the amount of data (a corpus of interview transcripts typically runs into the hundreds of pages; fieldnotes can easily top that), this chapter will also address time management and provide suggestions for dealing with chaos and reminders that feeling overwhelmed at the analysis stage is part of the process. By the end of the chapter, you should understand how “findings” are actually found.

The book concludes with a chapter dedicated to the effective presentation of data results. Chapter 20 covers the many ways that researchers communicate their studies to various audiences (academic, personal, political), what elements must be included in these various publications, and the hallmarks of excellent qualitative research that various audiences will be expecting. Because qualitative researchers are motivated by understanding and conveying meaning , effective communication is not only an essential skill but a fundamental facet of the entire research project. Ethnographers must be able to convey a certain sense of verisimilitude , the appearance of true reality. Those employing interviews must faithfully depict the key meanings of the people they interviewed in a way that rings true to those people, even if the end result surprises them. And all researchers must strive for clarity in their publications so that various audiences can understand what was found and why it is important.

The book concludes with a short chapter ( chapter 21 ) discussing the value of qualitative research. At the very end of this book, you will find a glossary of terms. I recommend you make frequent use of the glossary and add to each entry as you find examples. Although the entries are meant to be simple and clear, you may also want to paraphrase the definition—make it “make sense” to you, in other words. In addition to the standard reference list (all works cited here), you will find various recommendations for further reading at the end of many chapters. Some of these recommendations will be examples of excellent qualitative research, indicated with an asterisk (*) at the end of the entry. As they say, a picture is worth a thousand words. A good example of qualitative research can teach you more about conducting research than any textbook can (this one included). I highly recommend you select one to three examples from these lists and read them along with the textbook.

A final note on the choice of examples – you will note that many of the examples used in the text come from research on college students. This is for two reasons. First, as most of my research falls in this area, I am most familiar with this literature and have contacts with those who do research here and can call upon them to share their stories with you. Second, and more importantly, my hope is that this textbook reaches a wide audience of beginning researchers who study widely and deeply across the range of what can be known about the social world (from marine resources management to public policy to nursing to political science to sexuality studies and beyond). It is sometimes difficult to find examples that speak to all those research interests, however. A focus on college students is something that all readers can understand and, hopefully, appreciate, as we are all now or have been at some point a college student.

Patton’s Ten Suggestions for Doing Qualitative Research

The following ten suggestions were made by Michael Quinn Patton in his massive textbooks Qualitative Research and Evaluations Methods . This book is highly recommended for those of you who want more than an introduction to qualitative methods. It is the book I relied on heavily when I was a graduate student, although it is much easier to “dip into” when necessary than to read through as a whole. Patton is asked for “just one bit of advice” for a graduate student considering using qualitative research methods for their dissertation. Here are his top ten responses, in short form, heavily paraphrased, and with additional comments and emphases from me:

Make sure that a qualitative approach fits the research question. The following are the kinds of questions that call out for qualitative methods or where qualitative methods are particularly appropriate: questions about people’s experiences or how they make sense of those experiences; studying a person in their natural environment; researching a phenomenon so unknown that it would be impossible to study it with standardized instruments or other forms of quantitative data collection.
Study qualitative research by going to the original sources for the design and analysis appropriate to the particular approach you want to take (e.g., read Glaser and Straus if you are using grounded theory )
Find a dissertation adviser who understands or at least who will support your use of qualitative research methods. You are asking for trouble if your entire committee is populated by quantitative researchers, even if they are all very knowledgeable about the subject or focus of your study (maybe even more so if they are!)
Really work on design. Doing qualitative research effectively takes a lot of planning. Even if things are more flexible than in quantitative research, a good design is absolutely essential when starting out.
Practice data collection techniques, particularly interviewing and observing. There is definitely a set of learned skills here! Do not expect your first interview to be perfect. You will continue to grow as a researcher the more interviews you conduct, and you will probably come to understand yourself a bit more in the process, too. This is not easy, despite what others who don’t work with qualitative methods may assume (and tell you!)
Have a plan for analysis before you begin data collection. This is often a requirement in IRB protocols , although you can get away with writing something fairly simple. And even if you are taking an approach, such as grounded theory, that pushes you to remain fairly open-minded during the data collection process, you still want to know what you will be doing with all the data collected – creating a codebook? Writing analytical memos? Comparing cases? Having a plan in hand will also help prevent you from collecting too much extraneous data.
Be prepared to confront controversies both within the qualitative research community and between qualitative research and quantitative research. Don’t be naïve about this – qualitative research, particularly some approaches, will be derided by many more “positivist” researchers and audiences. For example, is an “n” of 1 really sufficient? Yes! But not everyone will agree.
Do not make the mistake of using qualitative research methods because someone told you it was easier, or because you are intimidated by the math required of statistical analyses. Qualitative research is difficult in its own way (and many would claim much more time-consuming than quantitative research). Do it because you are convinced it is right for your goals, aims, and research questions.
Find a good support network. This could be a research mentor, or it could be a group of friends or colleagues who are also using qualitative research, or it could be just someone who will listen to you work through all of the issues you will confront out in the field and during the writing process. Even though qualitative research often involves human subjects, it can be pretty lonely. A lot of times you will feel like you are working without a net. You have to create one for yourself. Take care of yourself.
And, finally, in the words of Patton, “Prepare to be changed. Looking deeply at other people’s lives will force you to look deeply at yourself.”
We will actually spend an entire chapter ( chapter 3 ) looking at this question in much more detail! ↵
Note that this might have been news to Europeans at the time, but many other societies around the world had also come to this conclusion through observation. There is often a tendency to equate “the scientific revolution” with the European world in which it took place, but this is somewhat misleading. ↵
Historians are a special case here. Historians have scrupulously and rigorously investigated the social world, but not for the purpose of understanding general laws about how things work, which is the point of scientific empirical research. History is often referred to as an idiographic field of study, meaning that it studies things that happened or are happening in themselves and not for general observations or conclusions. ↵
Don’t worry, we’ll spend more time later in this book unpacking the meaning of ethnography and other terms that are important here. Note the available glossary ↵

An approach to research that is “multimethod in focus, involving an interpretative, naturalistic approach to its subject matter. This means that qualitative researchers study things in their natural settings, attempting to make sense of, or interpret, phenomena in terms of the meanings people bring to them. Qualitative research involves the studied use and collection of a variety of empirical materials – case study, personal experience, introspective, life story, interview, observational, historical, interactional, and visual texts – that describe routine and problematic moments and meanings in individuals’ lives." ( Denzin and Lincoln 2005:2 ). Contrast with quantitative research .

In contrast to methodology, methods are more simply the practices and tools used to collect and analyze data. Examples of common methods in qualitative research are interviews , observations , and documentary analysis . One’s methodology should connect to one’s choice of methods, of course, but they are distinguishable terms. See also methodology .

A proposed explanation for an observation, phenomenon, or scientific problem that can be tested by further investigation. The positing of a hypothesis is often the first step in quantitative research but not in qualitative research. Even when qualitative researchers offer possible explanations in advance of conducting research, they will tend to not use the word “hypothesis” as it conjures up the kind of positivist research they are not conducting.

The foundational question to be addressed by the research study. This will form the anchor of the research design, collection, and analysis. Note that in qualitative research, the research question may, and probably will, alter or develop during the course of the research.

An approach to research that collects and analyzes numerical data for the purpose of finding patterns and averages, making predictions, testing causal relationships, and generalizing results to wider populations. Contrast with qualitative research .

Data collection that takes place in real-world settings, referred to as “the field;” a key component of much Grounded Theory and ethnographic research. Patton ( 2002 ) calls fieldwork “the central activity of qualitative inquiry” where “‘going into the field’ means having direct and personal contact with people under study in their own environments – getting close to people and situations being studied to personally understand the realities of minutiae of daily life” (48).

The people who are the subjects of a qualitative study. In interview-based studies, they may be the respondents to the interviewer; for purposes of IRBs, they are often referred to as the human subjects of the research.

The branch of philosophy concerned with knowledge. For researchers, it is important to recognize and adopt one of the many distinguishing epistemological perspectives as part of our understanding of what questions research can address or fully answer. See, e.g., constructivism , subjectivism, and objectivism .

An approach that refutes the possibility of neutrality in social science research. All research is “guided by a set of beliefs and feelings about the world and how it should be understood and studied” (Denzin and Lincoln 2005: 13). In contrast to positivism , interpretivism recognizes the social constructedness of reality, and researchers adopting this approach focus on capturing interpretations and understandings people have about the world rather than “the world” as it is (which is a chimera).

The cluster of data-collection tools and techniques that involve observing interactions between people, the behaviors, and practices of individuals (sometimes in contrast to what they say about how they act and behave), and cultures in context. Observational methods are the key tools employed by ethnographers and Grounded Theory .

Research based on data collected and analyzed by the research (in contrast to secondary “library” research).

The process of selecting people or other units of analysis to represent a larger population. In quantitative research, this representation is taken quite literally, as statistically representative. In qualitative research, in contrast, sample selection is often made based on potential to generate insight about a particular topic or phenomenon.

A method of data collection in which the researcher asks the participant questions; the answers to these questions are often recorded and transcribed verbatim. There are many different kinds of interviews - see also semistructured interview , structured interview , and unstructured interview .

The specific group of individuals that you will collect data from. Contrast population.

The practice of being conscious of and reflective upon one’s own social location and presence when conducting research. Because qualitative research often requires interaction with live humans, failing to take into account how one’s presence and prior expectations and social location affect the data collected and how analyzed may limit the reliability of the findings. This remains true even when dealing with historical archives and other content. Who we are matters when asking questions about how people experience the world because we, too, are a part of that world.

The science and practice of right conduct; in research, it is also the delineation of moral obligations towards research participants, communities to which we belong, and communities in which we conduct our research.

An administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated. The IRB is charged with the responsibility of reviewing all research involving human participants. The IRB is concerned with protecting the welfare, rights, and privacy of human subjects. The IRB has the authority to approve, disapprove, monitor, and require modifications in all research activities that fall within its jurisdiction as specified by both the federal regulations and institutional policy.

Research, according to US federal guidelines, that involves “a living individual about whom an investigator (whether professional or student) conducting research: (1) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (2) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.”

One of the primary methodological traditions of inquiry in qualitative research, ethnography is the study of a group or group culture, largely through observational fieldwork supplemented by interviews. It is a form of fieldwork that may include participant-observation data collection. See chapter 14 for a discussion of deep ethnography.

A form of interview that follows a standard guide of questions asked, although the order of the questions may change to match the particular needs of each individual interview subject, and probing “follow-up” questions are often added during the course of the interview. The semi-structured interview is the primary form of interviewing used by qualitative researchers in the social sciences. It is sometimes referred to as an “in-depth” interview. See also interview and interview guide .

A method of observational data collection taking place in a natural setting; a form of fieldwork . The term encompasses a continuum of relative participation by the researcher (from full participant to “fly-on-the-wall” observer). This is also sometimes referred to as ethnography , although the latter is characterized by a greater focus on the culture under observation.

A research design that employs both quantitative and qualitative methods, as in the case of a survey supplemented by interviews.

An epistemological perspective that posits the existence of reality through sensory experience similar to empiricism but goes further in denying any non-sensory basis of thought or consciousness. In the social sciences, the term has roots in the proto-sociologist August Comte, who believed he could discern “laws” of society similar to the laws of natural science (e.g., gravity). The term has come to mean the kinds of measurable and verifiable science conducted by quantitative researchers and is thus used pejoratively by some qualitative researchers interested in interpretation, consciousness, and human understanding. Calling someone a “positivist” is often intended as an insult. See also empiricism and objectivism.

A place or collection containing records, documents, or other materials of historical interest; most universities have an archive of material related to the university’s history, as well as other “special collections” that may be of interest to members of the community.

A method of both data collection and data analysis in which a given content (textual, visual, graphic) is examined systematically and rigorously to identify meanings, themes, patterns and assumptions. Qualitative content analysis (QCA) is concerned with gathering and interpreting an existing body of material.

A word or short phrase that symbolically assigns a summative, salient, essence-capturing, and/or evocative attribute for a portion of language-based or visual data (Saldaña 2021:5).

Usually a verbatim written record of an interview or focus group discussion.

The primary form of data for fieldwork , participant observation , and ethnography . These notes, taken by the researcher either during the course of fieldwork or at day’s end, should include as many details as possible on what was observed and what was said. They should include clear identifiers of date, time, setting, and names (or identifying characteristics) of participants.

The process of labeling and organizing qualitative data to identify different themes and the relationships between them; a way of simplifying data to allow better management and retrieval of key themes and illustrative passages. See coding frame and codebook.

A methodological tradition of inquiry and approach to analyzing qualitative data in which theories emerge from a rigorous and systematic process of induction. This approach was pioneered by the sociologists Glaser and Strauss (1967). The elements of theory generated from comparative analysis of data are, first, conceptual categories and their properties and, second, hypotheses or generalized relations among the categories and their properties – “The constant comparing of many groups draws the [researcher’s] attention to their many similarities and differences. Considering these leads [the researcher] to generate abstract categories and their properties, which, since they emerge from the data, will clearly be important to a theory explaining the kind of behavior under observation.” (36).

A detailed description of any proposed research that involves human subjects for review by IRB. The protocol serves as the recipe for the conduct of the research activity. It includes the scientific rationale to justify the conduct of the study, the information necessary to conduct the study, the plan for managing and analyzing the data, and a discussion of the research ethical issues relevant to the research. Protocols for qualitative research often include interview guides, all documents related to recruitment, informed consent forms, very clear guidelines on the safekeeping of materials collected, and plans for de-identifying transcripts or other data that include personal identifying information.

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Original research article, microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug.

1 School of Internet of Things Engineering, Institute of Advanced Technology, Jiangnan University, Wuxi, China
2 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China
3 Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing, China
4 School of Biotechnology, the Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations.

1 Introduction

Cytotoxicity assays are pivotal in evaluating cellular damage induced by drugs, playing a critical role in the drug development process and safety evaluation ( Parboosing et al., 2017 ; Zhang and Wan, 2022 ). These assays facilitate the determination of a drug’s safety profile, therapeutic window, and potential side effects, thus informing drug design, judicious usage, and toxicity risk assessment. They are instrumental in detecting adverse effects and providing essential data for the secure administration of drugs ( Niles et al., 2008 ; Vaucher et al., 2010 ).

The relationship between drug concentration, an independent factor influencing cytotoxicity ( Chan et al., 2002 ; Radko et al., 2013 ), and cytotoxicity is essential to optimize therapeutic efficacy and minimize adverse effects. Understanding the dose-response relationship is pivotal for researchers to strike a delicate balance between drug efficacy and safety, thereby ensuring judicious drug utilization that curtails potential risks. Cancer cells differ from normal cells in many ways, one of which is that they grow and divide very rapidly. In response to this characteristic, a number of cytotoxic drugs have been developed that target rapidly proliferating cancer cells and inhibit their growth and proliferation by interfering with their DNA synthesis or cell division processes ( McQuade et al., 2017 ; Dongsar et al., 2023 ). However, cytotoxic drugs do not completely discriminate between cancer cells and normal cells ( Tofzikovskaya et al., 2015 ). Mitomycin-C is an example of a cell cycle-specific chemotherapeutic agent widely used in oncology and cytotoxicity research ( Tomasz, 1995 ; Zhang et al., 2019 ; Park et al., 2021 ), predominantly acting on the G2 and M phases to impede DNA synthesis and cell division, thereby arresting cancer cell proliferation. Despite its efficacy against various cancer cell types, mitomycin-c’s potential toxicity to normal cells necessitates rigorous dose regulation and vigilant monitoring for adverse effects. Consequently, assessing the drug concentration-inhibition relationship is an indispensable component of cytotoxicity studies.

To accurately evaluate drug impacts on cell viability, two common techniques are employed: real-time cellular analysis (RTCA) and CCK-8 assays ( Cai et al., 2019 ). RTCA offers real-time, non-invasive monitoring of cellular dynamics, but with limited application scope and higher equipment costs ( Yan et al., 2018 ). Conversely, the CCK-8 assay, a standard in cytotoxicity tests, facilitates straightforward colorimetric measurements and is versatile across various cell lines ( Wang et al., 2015 ; Liu et al., 2018 ; Wang et al., 2018 ). However, to ensure a sufficient reaction, the CCK-8 method requires a certain incubation time for the reaction, typically 1∼4 h.

While established cytotoxicity assays like CCK-8 and real-time cellular assays are well-developed, ongoing research is delving into novel assays tailored for diverse cellular contexts and specific experimental requirements. The investigation of cytotoxic mechanisms warrants detailed analysis in certain studies, whereas others prioritize the rapidity and precision of the assay’s readouts. Moreover, optical and electrical measurements can often complement each other’s results in the field of biosensing ( He et al., 2023 ). Microwave biosensors, as a new type of biosensor, are highly sensitive and correspondingly fast (their response time is usually only a few seconds to a few mins), allowing real-time results to be obtained in a short period of time ( Narang et al., 2018 ; Gao et al., 2021 ). Microwave biosensors’ compactness and lightweight design indeed make them ideal for portable device production. Their seamless integration with electronic circuits, coupled with appropriate algorithms, can lead to intelligent data processing products. To date, no attempt has been made to detect drug cytotoxicity using microwave resonance sensors. If the microwave biosensor can be used for cytotoxicity detection, it can complement the original method in terms of advantages and disadvantages. This wound also further broaden the application areas of microwave detection. Microwave biosensors for measuring cytotoxicity have the advantages of eliminating the need for cell staining, rapid detection, low cost, easy integration with matching circuits, and small sample size. Microwave sensors based on resonant elements are very sensitive to the dielectric constant and loss angle tangent of the surrounding medium ( Muñoz-Enano et al., 2020 ), and have been widely used in the fields of biosensing. Researchers have demonstrated that it has promising applications in bacteria detection ( Narang et al., 2018 ; Jain et al., 2020 ; Jain et al., 2021 ), blood glucose detection ( Yilmaz et al., 2019 ; Kandwal et al., 2020 ; Nazli Kazemi anLight, 2023 ), and many other areas. Since the key to the endpoint method of evaluating drug cytotoxicity is to determine the number of surviving cells at the end of the experiment ( Adan et al., 2016 ), and there have been studies on the differences in dielectric properties of cell solutions at different concentrations ( Chen et al., 2014 ), it has a certain degree of feasibility to do cytotoxicity testing with microwave sensors.

In this paper, we have designed and fabricated a microwave biosensor based on the integrated passive device (IPD) fabrication technology. IPD integrates different passive components (inductors, capacitors, resistors) in a single subcomponent, which is characterized by a small linewidth, precise substrate control, a high degree of integration and fewer parasitic effects ( Yu et al., 2019 ; Chu et al., 2020 ). Moreover, IPDs demonstrate enhanced stability compared to capacitive or resistive sensors ( Yu et al., 2021 ). The consolidation of multiple passive components onto a single chip allows IPDs to conserve space, diminish energy consumption, bolster system reliability and accuracy of measurements, and ease the transition to productization. Employing this biosensor, we assessed the impact of concentration on cytotoxicity using HepG2 cells as the model and Mitomycin-c as the chemotherapeutic agent. We determined OD450 values via the CCK-8 assay, which is the biological gold standard ( Zhou et al., 2018 ), as a control group for parallel experiments and verified the feasibility of cytotoxicity experiments using microwave sensors by mapping and comparing the curves of the two groups. In addition, we treated the cells with ultrapure water instead of phosphate buffered saline (PBS) in this experiment to verify the feasibility of this treatment in the microwave biosensor cell number measurement experiments.

2 Materials and methods

2.1 sensor design and analysis.

The proposed biosensor is a microwave IPD resonator, consisting of a spiral inductor and an interdigital capacitor, where changes in the electrical parameters of the surrounding medium, mainly the dielectric constant and the loss angle tangent can cause changes in the resonant frequency or the amplitude of the resonance peak. When designing microwave resonators, the relevant parameters and performance are usually adjusted by the capacitance section ( Zhu and Abbosh, 2016 ; Xu and Zhu, 2017 ). The spiral inductor of the proposed microwave sensor is pre-designed by our group ( Wang et al., 2023 ) and this work focuses on the design, optimization and simulation of the interdigital capacitor. By adjusting the corresponding capacitance structure, we can adjust the frequency sensitivity and amplitude sensitivity of the resonator. In the design of the interdigital capacitive structure, three schemes are considered, respectively, in a cross-shaped central periphery equally spaced increase of 1-turn, 2-turn and 3-turn copper strip lines as shown in Figures 1A–I, B-I, and C-I . The reflection coefficient (S 11 ) of the three resonators and the variation of the resonance peak amplitude in different loss angle tangent environments are simulated in the Advanced Design System 2020 (ADS). The Eq. (1) shows that the permittivity of a sample can be obtained by adding the real and imaginary permittivity:

Figure 1 . Simulation results of the sensor. (A) Interdigital capacitor with 1-turn, (A–I) structure, (A-II) S 11 , (A-III) resonance peak amplitude in different loss angle tangent. (B) Interdigital capacitor with 2-turns, (B–I) structure, (B-II) S 11 , (B-III) resonance peak amplitude in different loss angle tangent. (C) Interdigital capacitor with 3-turns, (C–I) structure, (C-II) S 11 , (C-III) resonance peak amplitude in different loss angle tangent.

The loss angle tangent is calculated from Eq. 2 :

Samples with varying cell concentrations can be characterized by using different values of the loss angle tangent. A change in the loss angle tangent indicates a change in the complex dielectric constant, which in turn affects the S 11 of the microwave resonator. It can be seen from Figures 1A–II , B-II, and C-II that as the number of turns increases, the resonant frequency decreases, the bandwidth decreases and the Q value decreases. High Q represents high energy storage capacity and frequency selectivity. In terms of sensitivity to the loss angle tangent, the structure of 2-turn shows the best performance as illustrated in Figures 1A–III , B-III, and C-III. Since the resonance amplitude is usually the preferred metric for this type of detection relative to the resonance frequency ( Jain et al., 2021 ), and combined with factors such as the size of the detection area, interdigital capacitor with 2-turns was finally selected as the biosensor.

Figure 2A delineates the capacitive section’s architecture and precise dimensions. Encircling the device, a spiral inductor integrated with air-bridge structures is observed, while at its nucleus lies an interdigital capacitor, composed of strip wires coiled around a cruciform framework. The strip lines boast a uniform size and interspace of 20 μm. Figure 2B shows the longitudinal layer structure of the sensor, from top to bottom, with a 4.5/0.5 µm Cu/Au top layer, a 1.8 μm copper interconnect layer containing air bridge structure which were introduced in the spiral inductor to increase the mutual inductance and decrease the signal transmission loss in the inductor, a 4.5/0.5 µm Cu/Au bottom layer, a 0.2 μm thick nitride dielectric layer with relative dielectric constant of 7.5 and a loss angle tangent of 0.0036, a 200 μm thick GaAs substrate layer with relative dielectric constant of 12.85 and a loss angle tangent of 0.0028. For the fabrication of our proposed biosensor, seed metal (Ti/Au) is sputtered with the thicknesses of 20/80 nm as for strengthened metallic adhesion. In the electroplating process, gold and copper are tightly bonded through the plating process and have excellent corrosion resistance and do not easily diffuse into the solution, thus they do not interfere with the cytotoxicity analysis of cells. The electric field condition of this resonator is simulated in High Frequency Structure Simulator 19.1(HFSS), and its horizontal E-field strength is shown in Figure 2C , where the E-field strength reaches 10 6 V/m in its core sensitive region. The highest electric field strengths reported so far in the paper are around 10 5 V/m ( Zarifi et al., 2017 ; Kumar et al., 2020 ). The device’s notably higher electric field strengths suggest enhanced penetration and sensitivity. Considering the actual measured solution droplet size, the longitudinal field strength distribution is also simulated, and the results are shown in Figure 2D , illustrating that the sensitive region can still achieve an electric field strength of 10 5 V/m at a height of 50 μm. High electric field strength in the horizontal and vertical directions reveals the good penetration capability of the device. Consequently, this allows for the use of larger droplet volumes when applying sample droplets, effectively minimizing random sampling errors. Figure 2E shows the equivalent circuit diagram of the device. The capacitance of the oxide layer between the base and the metal can be denoted as C ox , the resistance between the substrate and the ground can be denoted as R sub , the capacitance can be denoted as C sub , the parasitic resistance of the inductor can be denoted as R L , the parasitic conductance of the capacitance can be denoted as G . Through the equivalent circuit transformation, the whole device can be regarded as an LC resonator. The complex dielectric constant properties of the cell solution can be modeled using the Debye equation. The relationship between the measured microwave parameters of the cell solution and the complex dielectric constant can be expressed by Eq. (3) as ( Withayachumnankul et al., 2013 )

where △ ε ′ = ε s ′ − ε r ′ , △ ε ″ = ε s ″ − ε r ″ , △ f 0 = f s − f r and △ S 11 = S 11 s − S 11 r are the differences between the sample (with subscript s ) and the reference (with subscript r ) values, m 11 , m 12 , m 21 , m 22 is the parameters to be determined. In this experiment, a change in cell concentration would cause a change in the loss angle tangent, thus causing a change in △ S 11 .

Figure 2 . Device structure analysis and electric field simulation. (A) Overall device structure and dimensions of interdigital capacitance. (B) The hierarchical structure of the device. (C) Surface electric field distribution of devices. (D) Vertical electric field distribution. (E) Equivalent circuit diagram.

2.2 Preparation of biological sample

HepG2 cell line is used as the experimental cells which were purchased from the cell bank of the Chinese Academy of Science (Shanghai, China). It is a human hepatocellular carcinoma cell line commonly used in the study of molecular mechanisms, drug screening and treatment of liver cancer ( Elkady et al., 2022 ). The entire experimental procedure is illustrated in Figure 3 . After completing the cell resuscitation, we first performed a pre-experiment using the fabricated microwave biosensor for cell number measurement. We inoculated cells into rows A, B, D, and E of a 96-well plate with a concentration gradient of 100 cells per well to 200,000 cells per well in two-fold increments, and added.

Figure 3 . Cell culture and handling, addition of drugs and pre-preparation for measurements.

Dulbecco’s modified eagle medium (DMEM) to make them adherent to the bottom by incubating them for 24 h in a CO 2 incubator at 37 °C. After removing them from the incubator, we pipetted the DMEM from the A and B rows and washed them with PBS. After that, in row A, trypsin treatment was used to dissociate the cells from the bottom, and then 100 μL of PBS was injected into each well; in row B, the same trypsin treatment was used, and then 100 μL of ultrapure water was injected into each well. Rows D and E are used as backup groups. The PBS, trypsin solution and DMEM used in the experiments were purchased from Sangon Biotech (Shanghai, China). The cell culture incubator was purchased from Thermofishe (United States). Normally, in cell number experiments, cells are treated in PBS.In this study, ultrapure water was utilized to treat Group B based on several key considerations. In order to maintain an isotonic state with the cytosol, the ionic concentration of PBS buffer and cytosol is similar. This would result in the cells and the PBS potentially exhibiting similar electrical parameter characteristics, which will lead to a narrowing of the differences in electrical parameters caused by the concentration of the cells. Conversely, the contrast in ionic concentration between ultrapure water and the cell solution is likely to amplify the solution’s electrical parameter changes due to cellular quantity. On the other hand, cell water uptake and cell fluid exudation can result in a more uniform ionic distribution of the solution, thus mitigating random errors linked to small sample sizes. After completing the pre-experimental validation, we seeded 50,000 cells per well on a new 96-well plate, inoculated on row C, D and E as three parallel groups, and after 24 h of CO 2 thermostatic incubation for cell adhesion, drug administration commenced. In this experiment, we used mitomycin-c as an inhibitor of cell growth. Mitomycin-c was selected as the cell growth inhibitor for this experiment. It was initially dissolved in dimethyl sulfoxide before being prepared into a stock solution at various concentrations. This stock solution was then serially diluted with DMEM to create a two-fold concentration gradient ranging from 1.7 μmol/L to 40 μmol/L. Subsequently, 200 μL of DMEM containing varying concentrations of mitomycin-c was added to each well of the 96-well plate and incubated at 37°C in a CO 2 incubator for 48 h. Repeat the above steps and prepare the same 3 rows of cells on a new 96-well plate, with one set for OD450 optical measurements and the other set for microwave measurements. For microwave measurement groups, remove the DMEM with a pipette, wash it with PBS, inject 100 μL of ultrapure water into each well. After a period of resting, pipette 1.5 μL of solution and drop it on the sensor for detection. Since the proposed microwave biosensor performs cytotoxicity detection mainly by detecting the concentration of ions contained in the cells, it is unable to distinguish between live and dead cells. Therefore, it is important to ensure that dead cells are cleaned as completely as possible before measurement. Additionally, the ions in the drug can also affect the measurements, so it is important to ensure that the drug is completely purified. The mitomycin-c and dimethyl sulfoxide used were purchased from MedChemExpress (Shanghai, China).

2.3 Experimental environment

The experimental apparatus was positioned on an anti-static mat and comprised a Vector Network Analyzer (VNA, Ceyear, 3656B), the IPD device, coaxial cables, samples, and a pipette, as depicted in Figure 4A . At the heart of the IPD device lies the microwave resonator, detailed microstructurally in Figure 4C . The resonator’s two ports are connected by bonding wire to the corresponding input and output matching wires on the printed circuit board. Figure 4B schematically illustrates the assembled sensor. Its bottom is an aluminum block with screw holes for fixing holes, and the chip is first fixed on top of the aluminum block by screws, and then connected to the coaxial cable of the VNA through the Small A Type connector fixed on both sides. This meticulous assembly ensures the chip remains horizontally stable, mitigating positional errors. The coaxial cable itself is taped to the table to reduce measurement disruptions from any movement. During the measurement, 1.5 μL of solution was added to the middle sensing area with a pipette. To ensure uniform distribution and mitigate the risk of sample settling, each sample drawn from a 96-well plate via pipette is agitated by employing a larger pipette tip. In subsequent sample drops, it was found that when the droplet volume was equal to 2 μL or larger, the droplets were easy to be dispersed irregularly on the surface of the device leading to measurement failure due to destruction of the surface tension of the droplets. After each measurement, the liquid was sucked up with absorbent paper and was cleaned several times with ultrapure water to return the S 11 to the initial values to ensure that the next experiment was not affected. Since temperature and humidity affect the performance of semiconductor devices, we control and measure the temperature and humidity values, the measurements were carried out at an ambient temperature of 20°C∼21 °C and a humidity of 47 %RH∼48 %RH.

Figure 4 . Measuring platforms and fabricated sensor. (A) The measurement environment. (B) Device structure and assembly schematic. (C) Microscope image of the proposed sensor.

3 Results and discussion

3.1 pre-experimental results of cell number measurements.

Figure 5 shows the overall results of the cell number measurement experiment. In the cell number measurement pre-experiment, pictures of cells with concentration gradients from 6.4×10 4 /mL to 2×10 6 /mL were taken under the microscope as shown in Figure 5A∼F , which showed healthy growth and a clear concentration gradient. The cells with a concentration gradient from 1×10 4 /mL to 3.2×10 4 /mL did not show a marked difference due to the limited cell numbers, similar to 6.4×10 4 /mL. Figure 5G illustrates the cellular morphology in PBS, where a transition from wall-adherent irregular shapes to more defined round or ovoid forms is observed, predominantly existing as either single entities or aggregated clusters. Under this circumstance, a dynamic equilibrium of ion and water molecule exchange is established between the intracellular and extracellular environments, resulting in comparable ion concentrations. Figure 5H shows the status of the cells after 5 mins of exposure to ultrapure water. Due to the lower osmotic pressure of pure water compared to the cells, water enters the cells, causing them to swell or even dissolve. Cells lose their original morphological characteristics in pure water and become flattened, deformed or ruptured. This can lead to spillage of cell contents dispersed in ultrapure water. The measurements of the S 11 near the resonance peak of ten quantities of cells after treatment with ultrapure water are shown in Figure 5I . The peak value of the S 11 decreases with the increase of cell concentration. These measurements were plotted as points in Origin. It can be found that when the number of cells is too low (lower than 6.4 × 10 4 /mL), the measurements of microwave amplitude are similar, showing a deviation from the other groups and are similar to the measurements of ultrapure water. This may be due to inadequate cytosol exchange with external components when cell numbers are low, and the aspirated 1.5 μL solution may not contain cell membrane components. After selecting the mean of multiple measurements, we performed a linear fit to the mean data on the last six data as shown in Figure 5J . The error bars are based on the mean value, and the relationship between the amplitude of the resonance peak and the concentration of the cells can be characterized by y = 2.58549 × 10 −7 x-25.70623. R 2 is 0.99874, showing a good linear relationship. The corresponding detection and quantification limits (LOD&LOQ) of the proposed devices was calculated on the basis of following Eqs ( 4 , 5 ) ( Qiang et al., 2017 ) as 1.41×10 5 /mL and 4.23×10 5 /mL, respectively.

where SD is the standard deviation of the frequency response and m is the slope of the regression line. That means, the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value is 1.41×10 5 /mL, the lowest amount of analyte in a sample which can be quantitatively determined is 4.23×10 5 /mL. This experiment demonstrated that there is a linear relationship between the magnitude of the amplitude under the microwave resonator and the number of cells. Specifically, when the number of cells exceeds a certain threshold (6.4×10 4 /mL), the solution of adherent cells treated with ultrapure water shows this relationship. This experiment confirms that using this microwave sensor to measure cytotoxicity as an endpoint is feasible.

Figure 5 . Results of the pre-experiment on cell number measurement. Cells cultured in DMEM at a concentration of (A) 6.4×10 4 /mL, (B) 1.25×10 4 /mL, (C) 2.5×10 5 /mL, (D) 5×10 5 /mL, (E) 1×10 6 /mL, (F) 2×10 6 /mL. (G) Cells in PBS, and (H) cells in ultrapure water. (I) S 11 of different concentrations in ultrapure water. (J) Linear fitted results of cell concentration and magnitude in resonant frequency.

3.2 Measurements from drug inhibition experiments

The results of the drug concentration cytotoxicity assay measurements are presented in Figure 6 . Figure 6A demonstrates the cell growth after 48 h of culture with drug concentration ranging from 1.7 μM to 12.65 μM. It can be clearly seen that the number of live cells gradually decreased as the drug concentration increased, and the inhibition of cell growth by the drug can be assessed from the number of surviving live cells. The inhibitory capacity of mitomycin reaches its maximum at drug concentrations of approximately 9.5 μM. Higher concentrations have similar inhibitory effects to 9.5 μM. The cells were subjected to OD450 measurements, depicting the curves in Figure 6B . In addition, the curves of cell concentration and OD450 values were measured for HepG2, and the results are shown in Figure 6C which is similar to the results of the OD450 measurement of cell number in Figure 5J . Since OD450 values have a good linear relationship with cell concentration, OD450 measurements can be equated to cell concentration. Microwave resonance peak amplitude measurements were performed after ultrapure water treatment. A set of near-mean measurements was selected and their S 11 are plotted in Figure 6D . It can be observed that the amplitude of the resonance peak decreases by approximately 0.45 dB as the drug concentration increases from 1.70 μM to 12.65 μM. The relationship between amplitude and drug concentration was plotted in Figure 6E after an equal number of measurements were taken in three parallel groups and the mean value was selected. It can be seen that the microwave resonance amplitude measurements have similar results to the OD450 measurements. At higher drug concentrations, the resonance amplitude tends to a stable value. Therefore, it is feasible to use the resonance amplitude curve as an assessment index of drug toxicity. Various in vitro cytotoxicity assays are currently available including chromium release, bioluminescence, impedance, and flow cytometry ( Kiesgen et al., 2021 ), most of which are based on chemical methods such as fluorescent labelling, optical densitometry and radioactivity determination. These methods have their characteristics and scope of application as well as limitations, microwave sensor methods introduce a new possibility for cytotoxicity determination, and their comparison is presented in Table 1 . These methods can be divided into two main categories, optical and electrical, covering a wide range of cellular measurements. In terms of device size, microwave biosensors have the advantage of being small. Microwave methods are on a similar scale to flow cytometry in terms of the concentration of cells that can be processed. Microwave methods are characterized by a tiny sample capacity (0.8 μL∼ 2 μL) in addition to inheriting the advantages of electrical methods that do not require staining of cells.

Figure 6 . Results of cytotoxicity assay for different concentrations of drugs. (A) Microscopic images of cells cultured at different drug concentrations for 48 h and washed with PBS buffer to remove dead cells. (B) OD450 value detection of live cells after 48 h of action with different concentrations of Mitomycin-c. (C) Measurement results of linear relationship between HepG2 concentration and OD450 value. (D) Measurement results of S 11 after drug concentration 1.7 μM∼40.0 μM action. (E) Microwave amplitude detection of living cells in aqueous solutions of Mitomycin-c with different concentrations after 48 h of action.

Table 1 . Summaries of existing cytotoxicity assays.

3.3 Experimental principles

The measurement mechanism of this experiment is divided into two main parts. The first part is cellular water uptake and subsequent rupture as shown in Figure 7A . When a cell is placed in ultrapure water, the concentration of the solution inside the cell is relatively high, while the concentration of the solution in ultrapure water is extremely low. Osmotic forces drive water molecules from the exterior into the cell, causing a volumetric expansion of the cell, a phenomenon termed cellular water absorption. However, if the cell absorbs more water molecules than it can hold, the increased internal pressure may cause the cell membrane to rupture. This typically happens when the cell membrane’s elastic limit is surpassed. After mechanical shaking, the broken cell membrane and various ions within the cell are dispersed relatively uniformly in solution. Differences in the number of cells can lead to differences in the final total ion concentration of the solution, as the cells are treated with equal amounts of ultrapure water. It should be noted that the number of cells should not be too high, otherwise they may not all rupture completely after absorbing water.

Figure 7 . Experimental principles. (A) Cell rupture in ultrapure water. (B) Measurement of sample in biosensor.

The second part is the principle of sample detection by the microwave biosensor as shown in Figure 7B . The cytosol contains a variety of ions, with sodium, potassium and chloride ions making up a large proportion. The effect of ion concentration on dielectric properties has been studied extensively, e.g., an increase in the concentration of sodium chloride leads to a decrease in the loss angle tangent ( Wang et al., 2013 ; Dandan et al., 2015 ). When the concentrations of sodium chloride and potassium chloride solutions are below a certain value, the dielectric properties of the solutions are similar to those of pure water, and only when they are above a certain value do the dielectric properties show a clear trend ( Eldamak et al., 2020 ). The loss angle tangent describes the nature of the ability of a material to absorb electromagnetic waves and is related to the energy loss in the material. As the concentration of a solution increases, so does the number of solute molecules or ions. At lower concentrations, the ions in the solution have a weaker ability to absorb electromagnetic waves, resulting in a larger loss angle tangent. However, as the concentration increases, the polarization effect of the ions in the solution increases, making the solution less able to absorb electromagnetic waves, resulting in a decrease in the loss angle tangent. Changes in the loss angle tangent affect the degree of microwave attenuation in the solution and the resonance peak of the resonator. When the solution is dropped onto the capacitive area of the microwave resonator, the medium surrounding the capacitive area changes, and the microwave biosensor detects this change sensitively and rapidly. The VNA sends a microwave signal over a set frequency range and measures the amplitude and phase of the reflected and transmitted signals. By varying the frequency and recording the corresponding signal response, data on the S 11 can be obtained. Further, the VNA can be connected to a computer to efficiently detect changes in the analyzed parameters using the corresponding software.

4 Conclusion

In this work, a microwave resonant sensor based on an integrated passive device is presented. The device can be used for cell number detection and further, for the assessment of the degree of cell growth inhibition by drug concentration. The sensor’s capability to detect cytotoxicity was validated against the biological gold standard, the CCK-8 assay. Unlike the usual PBS treatment of cells, ultrapure water was used to treat the cells in this experiment, offering an innovative approach for cell sensing via microwave technology. This novel method provides rapid, precise, and miniaturized cytotoxicity assessments, suitable for various applications. Future enhancements should concentrate on minimizing random detection errors through appropriate peripheral matching circuits and improving sensor sensitivity via structural design modifications. The improvement of the device structure relies mainly on the optimization of the interdigital capacitance. The matching of microwave biosensors with electronic circuits and the introduction of algorithms can result in a miniaturized smart device.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

Ethics statement

Ethical approval was not required for the studies on humans in accordance with the local legislation and institutional requirements because only commercially available established cell lines were used. Ethical approval was not required for the studies on animals in accordance with the local legislation and institutional requirements because only commercially available established cell lines were used.

Author contributions

J-MZ: Writing–original draft, Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Software, Validation, Visualization. Y-KW: Writing–review and editing, Methodology, Software. B-WS: Writing–review and editing, Methodology. Y-XW: Writing–original draft, Validation. Y-FJ: Writing–review and editing, Supervision. G-LY: Writing–review and editing, Supervision. X-DG: Writing–review and editing, Supervision. TQ: Writing–review and editing, Supervision, Conceptualization, Funding acquisition, Project administration, Resources, Visualization.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research is supported by National Natural Science Foundation of China (Grant No. 61801146), Project funded by China Postdoctoral Science Foundation (Grant No. 2021M691284), Postgraduate Research and Practice Innovation Program of Jiangsu Province (Grant No. SJCX23_1226), and Open Project of the Key Laboratory of Nanodevices and Applications, Chinese Academy of Sciences (Grant No. 22ZS07).

Acknowledgments

The authors acknowledge helpful conversations regarding the interpretation of these data with Prof. Xiaoman Zhou (School of Biotechnology, Jiangnan University, Wuxi, China). The sample of Figure 3 is designed by macrovector/Freepik.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: cytotoxicity assay, microwave sensors, live cells, drug concentrations, growth inhibition

Citation: Zhao J-M, Wang Y-K, Shi B-W, Wang Y-X, Jiang Y-F, Yang G-L, Gao X-D and Qiang T (2024) Microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug. Front. Bioeng. Biotechnol. 12:1398189. doi: 10.3389/fbioe.2024.1398189

Received: 09 March 2024; Accepted: 23 April 2024; Published: 13 May 2024.

Reviewed by:

Copyright © 2024 Zhao, Wang, Shi, Wang, Jiang, Yang, Gao and Qiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Xiao-Dong Gao, [email protected] ; Tian Qiang, [email protected]

This article is part of the Research Topic

Insights in Biosensors and Biomolecular Electronics 2024: Novel Developments, Current Challenges, and Future Perspectives

Cultural Relativity and Acceptance of Embryonic Stem Cell Research

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There is a debate about the ethical implications of using human embryos in stem cell research, which can be influenced by cultural, moral, and social values. This paper argues for an adaptable framework to accommodate diverse cultural and religious perspectives. By using an adaptive ethics model, research protections can reflect various populations and foster growth in stem cell research possibilities.

INTRODUCTION

Stem cell research combines biology, medicine, and technology, promising to alter health care and the understanding of human development. Yet, ethical contention exists because of individuals’ perceptions of using human embryos based on their various cultural, moral, and social values. While these disagreements concerning policy, use, and general acceptance have prompted the development of an international ethics policy, such a uniform approach can overlook the nuanced ethical landscapes between cultures. With diverse viewpoints in public health, a single global policy, especially one reflecting Western ethics or the ethics prevalent in high-income countries, is impractical. This paper argues for a culturally sensitive, adaptable framework for the use of embryonic stem cells. Stem cell policy should accommodate varying ethical viewpoints and promote an effective global dialogue. With an extension of an ethics model that can adapt to various cultures, we recommend localized guidelines that reflect the moral views of the people those guidelines serve.

Stem cells, characterized by their unique ability to differentiate into various cell types, enable the repair or replacement of damaged tissues. Two primary types of stem cells are somatic stem cells (adult stem cells) and embryonic stem cells. Adult stem cells exist in developed tissues and maintain the body’s repair processes. [1] Embryonic stem cells (ESC) are remarkably pluripotent or versatile, making them valuable in research. [2] However, the use of ESCs has sparked ethics debates. Considering the potential of embryonic stem cells, research guidelines are essential. The International Society for Stem Cell Research (ISSCR) provides international stem cell research guidelines. They call for “public conversations touching on the scientific significance as well as the societal and ethical issues raised by ESC research.” [3] The ISSCR also publishes updates about culturing human embryos 14 days post fertilization, suggesting local policies and regulations should continue to evolve as ESC research develops. [4] Like the ISSCR, which calls for local law and policy to adapt to developing stem cell research given cultural acceptance, this paper highlights the importance of local social factors such as religion and culture.

I. Global Cultural Perspective of Embryonic Stem Cells

Views on ESCs vary throughout the world. Some countries readily embrace stem cell research and therapies, while others have stricter regulations due to ethical concerns surrounding embryonic stem cells and when an embryo becomes entitled to moral consideration. The philosophical issue of when the “someone” begins to be a human after fertilization, in the morally relevant sense, [5] impacts when an embryo becomes not just worthy of protection but morally entitled to it. The process of creating embryonic stem cell lines involves the destruction of the embryos for research. [6] Consequently, global engagement in ESC research depends on social-cultural acceptability.

a. US and Rights-Based Cultures

In the United States, attitudes toward stem cell therapies are diverse. The ethics and social approaches, which value individualism, [7] trigger debates regarding the destruction of human embryos, creating a complex regulatory environment. For example, the 1996 Dickey-Wicker Amendment prohibited federal funding for the creation of embryos for research and the destruction of embryos for “more than allowed for research on fetuses in utero.” [8] Following suit, in 2001, the Bush Administration heavily restricted stem cell lines for research. However, the Stem Cell Research Enhancement Act of 2005 was proposed to help develop ESC research but was ultimately vetoed. [9] Under the Obama administration, in 2009, an executive order lifted restrictions allowing for more development in this field. [10] The flux of research capacity and funding parallels the different cultural perceptions of human dignity of the embryo and how it is socially presented within the country’s research culture. [11]

b. Ubuntu and Collective Cultures

African bioethics differs from Western individualism because of the different traditions and values. African traditions, as described by individuals from South Africa and supported by some studies in other African countries, including Ghana and Kenya, follow the African moral philosophies of Ubuntu or Botho and Ukama , which “advocates for a form of wholeness that comes through one’s relationship and connectedness with other people in the society,” [12] making autonomy a socially collective concept. In this context, for the community to act autonomously, individuals would come together to decide what is best for the collective. Thus, stem cell research would require examining the value of the research to society as a whole and the use of the embryos as a collective societal resource. If society views the source as part of the collective whole, and opposes using stem cells, compromising the cultural values to pursue research may cause social detachment and stunt research growth. [13] Based on local culture and moral philosophy, the permissibility of stem cell research depends on how embryo, stem cell, and cell line therapies relate to the community as a whole. Ubuntu is the expression of humanness, with the person’s identity drawn from the “’I am because we are’” value. [14] The decision in a collectivistic culture becomes one born of cultural context, and individual decisions give deference to others in the society.

Consent differs in cultures where thought and moral philosophy are based on a collective paradigm. So, applying Western bioethical concepts is unrealistic. For one, Africa is a diverse continent with many countries with different belief systems, access to health care, and reliance on traditional or Western medicines. Where traditional medicine is the primary treatment, the “’restrictive focus on biomedically-related bioethics’” [is] problematic in African contexts because it neglects bioethical issues raised by traditional systems.” [15] No single approach applies in all areas or contexts. Rather than evaluating the permissibility of ESC research according to Western concepts such as the four principles approach, different ethics approaches should prevail.

Another consideration is the socio-economic standing of countries. In parts of South Africa, researchers have not focused heavily on contributing to the stem cell discourse, either because it is not considered health care or a health science priority or because resources are unavailable. [16] Each country’s priorities differ given different social, political, and economic factors. In South Africa, for instance, areas such as maternal mortality, non-communicable diseases, telemedicine, and the strength of health systems need improvement and require more focus [17] Stem cell research could benefit the population, but it also could divert resources from basic medical care. Researchers in South Africa adhere to the National Health Act and Medicines Control Act in South Africa and international guidelines; however, the Act is not strictly enforced, and there is no clear legislation for research conduct or ethical guidelines. [18]

Some parts of Africa condemn stem cell research. For example, 98.2 percent of the Tunisian population is Muslim. [19] Tunisia does not permit stem cell research because of moral conflict with a Fatwa. Religion heavily saturates the regulation and direction of research. [20] Stem cell use became permissible for reproductive purposes only recently, with tight restrictions preventing cells from being used in any research other than procedures concerning ART/IVF. Their use is conditioned on consent, and available only to married couples. [21] The community's receptiveness to stem cell research depends on including communitarian African ethics.

c. Asia

Some Asian countries also have a collective model of ethics and decision making. [22] In China, the ethics model promotes a sincere respect for life or human dignity, [23] based on protective medicine. This model, influenced by Traditional Chinese Medicine (TCM), [24] recognizes Qi as the vital energy delivered via the meridians of the body; it connects illness to body systems, the body’s entire constitution, and the universe for a holistic bond of nature, health, and quality of life. [25] Following a protective ethics model, and traditional customs of wholeness, investment in stem cell research is heavily desired for its applications in regenerative therapies, disease modeling, and protective medicines. In a survey of medical students and healthcare practitioners, 30.8 percent considered stem cell research morally unacceptable while 63.5 percent accepted medical research using human embryonic stem cells. Of these individuals, 89.9 percent supported increased funding for stem cell research. [26] The scientific community might not reflect the overall population. From 1997 to 2019, China spent a total of $576 million (USD) on stem cell research at 8,050 stem cell programs, increased published presence from 0.6 percent to 14.01 percent of total global stem cell publications as of 2014, and made significant strides in cell-based therapies for various medical conditions. [27] However, while China has made substantial investments in stem cell research and achieved notable progress in clinical applications, concerns linger regarding ethical oversight and transparency. [28] For example, the China Biosecurity Law, promoted by the National Health Commission and China Hospital Association, attempted to mitigate risks by introducing an institutional review board (IRB) in the regulatory bodies. 5800 IRBs registered with the Chinese Clinical Trial Registry since 2021. [29] However, issues still need to be addressed in implementing effective IRB review and approval procedures.

The substantial government funding and focus on scientific advancement have sometimes overshadowed considerations of regional cultures, ethnic minorities, and individual perspectives, particularly evident during the one-child policy era. As government policy adapts to promote public stability, such as the change from the one-child to the two-child policy, [30] research ethics should also adapt to ensure respect for the values of its represented peoples.

Japan is also relatively supportive of stem cell research and therapies. Japan has a more transparent regulatory framework, allowing for faster approval of regenerative medicine products, which has led to several advanced clinical trials and therapies. [31] South Korea is also actively engaged in stem cell research and has a history of breakthroughs in cloning and embryonic stem cells. [32] However, the field is controversial, and there are issues of scientific integrity. For example, the Korean FDA fast-tracked products for approval, [33] and in another instance, the oocyte source was unclear and possibly violated ethical standards. [34] Trust is important in research, as it builds collaborative foundations between colleagues, trial participant comfort, open-mindedness for complicated and sensitive discussions, and supports regulatory procedures for stakeholders. There is a need to respect the culture’s interest, engagement, and for research and clinical trials to be transparent and have ethical oversight to promote global research discourse and trust.

d. Middle East

Countries in the Middle East have varying degrees of acceptance of or restrictions to policies related to using embryonic stem cells due to cultural and religious influences. Saudi Arabia has made significant contributions to stem cell research, and conducts research based on international guidelines for ethical conduct and under strict adherence to guidelines in accordance with Islamic principles. Specifically, the Saudi government and people require ESC research to adhere to Sharia law. In addition to umbilical and placental stem cells, [35] Saudi Arabia permits the use of embryonic stem cells as long as they come from miscarriages, therapeutic abortions permissible by Sharia law, or are left over from in vitro fertilization and donated to research. [36] Laws and ethical guidelines for stem cell research allow the development of research institutions such as the King Abdullah International Medical Research Center, which has a cord blood bank and a stem cell registry with nearly 10,000 donors. [37] Such volume and acceptance are due to the ethical ‘permissibility’ of the donor sources, which do not conflict with religious pillars. However, some researchers err on the side of caution, choosing not to use embryos or fetal tissue as they feel it is unethical to do so. [38]

Jordan has a positive research ethics culture. [39] However, there is a significant issue of lack of trust in researchers, with 45.23 percent (38.66 percent agreeing and 6.57 percent strongly agreeing) of Jordanians holding a low level of trust in researchers, compared to 81.34 percent of Jordanians agreeing that they feel safe to participate in a research trial. [40] Safety testifies to the feeling of confidence that adequate measures are in place to protect participants from harm, whereas trust in researchers could represent the confidence in researchers to act in the participants’ best interests, adhere to ethical guidelines, provide accurate information, and respect participants’ rights and dignity. One method to improve trust would be to address communication issues relevant to ESC. Legislation surrounding stem cell research has adopted specific language, especially concerning clarification “between ‘stem cells’ and ‘embryonic stem cells’” in translation. [41] Furthermore, legislation “mandates the creation of a national committee… laying out specific regulations for stem-cell banking in accordance with international standards.” [42] This broad regulation opens the door for future global engagement and maintains transparency. However, these regulations may also constrain the influence of research direction, pace, and accessibility of research outcomes.

e. Europe

In the European Union (EU), ethics is also principle-based, but the principles of autonomy, dignity, integrity, and vulnerability are interconnected. [43] As such, the opportunity for cohesion and concessions between individuals’ thoughts and ideals allows for a more adaptable ethics model due to the flexible principles that relate to the human experience The EU has put forth a framework in its Convention for the Protection of Human Rights and Dignity of the Human Being allowing member states to take different approaches. Each European state applies these principles to its specific conventions, leading to or reflecting different acceptance levels of stem cell research. [44]

For example, in Germany, Lebenzusammenhang , or the coherence of life, references integrity in the unity of human culture. Namely, the personal sphere “should not be subject to external intervention.” [45] Stem cell interventions could affect this concept of bodily completeness, leading to heavy restrictions. Under the Grundgesetz, human dignity and the right to life with physical integrity are paramount. [46] The Embryo Protection Act of 1991 made producing cell lines illegal. Cell lines can be imported if approved by the Central Ethics Commission for Stem Cell Research only if they were derived before May 2007. [47] Stem cell research respects the integrity of life for the embryo with heavy specifications and intense oversight. This is vastly different in Finland, where the regulatory bodies find research more permissible in IVF excess, but only up to 14 days after fertilization. [48] Spain’s approach differs still, with a comprehensive regulatory framework. [49] Thus, research regulation can be culture-specific due to variations in applied principles. Diverse cultures call for various approaches to ethical permissibility. [50] Only an adaptive-deliberative model can address the cultural constructions of self and achieve positive, culturally sensitive stem cell research practices. [51]

II. Religious Perspectives on ESC

Embryonic stem cell sources are the main consideration within religious contexts. While individuals may not regard their own religious texts as authoritative or factual, religion can shape their foundations or perspectives.

The Qur'an states:

“And indeed We created man from a quintessence of clay. Then We placed within him a small quantity of nutfa (sperm to fertilize) in a safe place. Then We have fashioned the nutfa into an ‘alaqa (clinging clot or cell cluster), then We developed the ‘alaqa into mudgha (a lump of flesh), and We made mudgha into bones, and clothed the bones with flesh, then We brought it into being as a new creation. So Blessed is Allah, the Best of Creators.” [52]

Many scholars of Islam estimate the time of soul installment, marked by the angel breathing in the soul to bring the individual into creation, as 120 days from conception. [53] Personhood begins at this point, and the value of life would prohibit research or experimentation that could harm the individual. If the fetus is more than 120 days old, the time ensoulment is interpreted to occur according to Islamic law, abortion is no longer permissible. [54] There are a few opposing opinions about early embryos in Islamic traditions. According to some Islamic theologians, there is no ensoulment of the early embryo, which is the source of stem cells for ESC research. [55]

In Buddhism, the stance on stem cell research is not settled. The main tenets, the prohibition against harming or destroying others (ahimsa) and the pursuit of knowledge (prajña) and compassion (karuna), leave Buddhist scholars and communities divided. [56] Some scholars argue stem cell research is in accordance with the Buddhist tenet of seeking knowledge and ending human suffering. Others feel it violates the principle of not harming others. Finding the balance between these two points relies on the karmic burden of Buddhist morality. In trying to prevent ahimsa towards the embryo, Buddhist scholars suggest that to comply with Buddhist tenets, research cannot be done as the embryo has personhood at the moment of conception and would reincarnate immediately, harming the individual's ability to build their karmic burden. [57] On the other hand, the Bodhisattvas, those considered to be on the path to enlightenment or Nirvana, have given organs and flesh to others to help alleviate grieving and to benefit all. [58] Acceptance varies on applied beliefs and interpretations.

Catholicism does not support embryonic stem cell research, as it entails creation or destruction of human embryos. This destruction conflicts with the belief in the sanctity of life. For example, in the Old Testament, Genesis describes humanity as being created in God’s image and multiplying on the Earth, referencing the sacred rights to human conception and the purpose of development and life. In the Ten Commandments, the tenet that one should not kill has numerous interpretations where killing could mean murder or shedding of the sanctity of life, demonstrating the high value of human personhood. In other books, the theological conception of when life begins is interpreted as in utero, [59] highlighting the inviolability of life and its formation in vivo to make a religious point for accepting such research as relatively limited, if at all. [60] The Vatican has released ethical directives to help apply a theological basis to modern-day conflicts. The Magisterium of the Church states that “unless there is a moral certainty of not causing harm,” experimentation on fetuses, fertilized cells, stem cells, or embryos constitutes a crime. [61] Such procedures would not respect the human person who exists at these stages, according to Catholicism. Damages to the embryo are considered gravely immoral and illicit. [62] Although the Catholic Church officially opposes abortion, surveys demonstrate that many Catholic people hold pro-choice views, whether due to the context of conception, stage of pregnancy, threat to the mother’s life, or for other reasons, demonstrating that practicing members can also accept some but not all tenets. [63]

Some major Jewish denominations, such as the Reform, Conservative, and Reconstructionist movements, are open to supporting ESC use or research as long as it is for saving a life. [64] Within Judaism, the Talmud, or study, gives personhood to the child at birth and emphasizes that life does not begin at conception: [65]

“If she is found pregnant, until the fortieth day it is mere fluid,” [66]

Whereas most religions prioritize the status of human embryos, the Halakah (Jewish religious law) states that to save one life, most other religious laws can be ignored because it is in pursuit of preservation. [67] Stem cell research is accepted due to application of these religious laws.

We recognize that all religions contain subsets and sects. The variety of environmental and cultural differences within religious groups requires further analysis to respect the flexibility of religious thoughts and practices. We make no presumptions that all cultures require notions of autonomy or morality as under the common morality theory , which asserts a set of universal moral norms that all individuals share provides moral reasoning and guides ethical decisions. [68] We only wish to show that the interaction with morality varies between cultures and countries.

III. A Flexible Ethical Approach

The plurality of different moral approaches described above demonstrates that there can be no universally acceptable uniform law for ESC on a global scale. Instead of developing one standard, flexible ethical applications must be continued. We recommend local guidelines that incorporate important cultural and ethical priorities.

While the Declaration of Helsinki is more relevant to people in clinical trials receiving ESC products, in keeping with the tradition of protections for research subjects, consent of the donor is an ethical requirement for ESC donation in many jurisdictions including the US, Canada, and Europe. [69] The Declaration of Helsinki provides a reference point for regulatory standards and could potentially be used as a universal baseline for obtaining consent prior to gamete or embryo donation.

For instance, in Columbia University’s egg donor program for stem cell research, donors followed standard screening protocols and “underwent counseling sessions that included information as to the purpose of oocyte donation for research, what the oocytes would be used for, the risks and benefits of donation, and process of oocyte stimulation” to ensure transparency for consent. [70] The program helped advance stem cell research and provided clear and safe research methods with paid participants. Though paid participation or covering costs of incidental expenses may not be socially acceptable in every culture or context, [71] and creating embryos for ESC research is illegal in many jurisdictions, Columbia’s program was effective because of the clear and honest communications with donors, IRBs, and related stakeholders. This example demonstrates that cultural acceptance of scientific research and of the idea that an egg or embryo does not have personhood is likely behind societal acceptance of donating eggs for ESC research. As noted, many countries do not permit the creation of embryos for research.

Proper communication and education regarding the process and purpose of stem cell research may bolster comprehension and garner more acceptance. “Given the sensitive subject material, a complete consent process can support voluntary participation through trust, understanding, and ethical norms from the cultures and morals participants value. This can be hard for researchers entering countries of different socioeconomic stability, with different languages and different societal values. [72]

An adequate moral foundation in medical ethics is derived from the cultural and religious basis that informs knowledge and actions. [73] Understanding local cultural and religious values and their impact on research could help researchers develop humility and promote inclusion.

IV. Concerns

Some may argue that if researchers all adhere to one ethics standard, protection will be satisfied across all borders, and the global public will trust researchers. However, defining what needs to be protected and how to define such research standards is very specific to the people to which standards are applied. We suggest that applying one uniform guide cannot accurately protect each individual because we all possess our own perceptions and interpretations of social values. [74] Therefore, the issue of not adjusting to the moral pluralism between peoples in applying one standard of ethics can be resolved by building out ethics models that can be adapted to different cultures and religions.

Other concerns include medical tourism, which may promote health inequities. [75] Some countries may develop and approve products derived from ESC research before others, compromising research ethics or drug approval processes. There are also concerns about the sale of unauthorized stem cell treatments, for example, those without FDA approval in the United States. Countries with robust research infrastructures may be tempted to attract medical tourists, and some customers will have false hopes based on aggressive publicity of unproven treatments. [76]

For example, in China, stem cell clinics can market to foreign clients who are not protected under the regulatory regimes. Companies employ a marketing strategy of “ethically friendly” therapies. Specifically, in the case of Beike, China’s leading stem cell tourism company and sprouting network, ethical oversight of administrators or health bureaus at one site has “the unintended consequence of shifting questionable activities to another node in Beike's diffuse network.” [77] In contrast, Jordan is aware of stem cell research’s potential abuse and its own status as a “health-care hub.” Jordan’s expanded regulations include preserving the interests of individuals in clinical trials and banning private companies from ESC research to preserve transparency and the integrity of research practices. [78]

The social priorities of the community are also a concern. The ISSCR explicitly states that guidelines “should be periodically revised to accommodate scientific advances, new challenges, and evolving social priorities.” [79] The adaptable ethics model extends this consideration further by addressing whether research is warranted given the varying degrees of socioeconomic conditions, political stability, and healthcare accessibilities and limitations. An ethical approach would require discussion about resource allocation and appropriate distribution of funds. [80]

While some religions emphasize the sanctity of life from conception, which may lead to public opposition to ESC research, others encourage ESC research due to its potential for healing and alleviating human pain. Many countries have special regulations that balance local views on embryonic personhood, the benefits of research as individual or societal goods, and the protection of human research subjects. To foster understanding and constructive dialogue, global policy frameworks should prioritize the protection of universal human rights, transparency, and informed consent. In addition to these foundational global policies, we recommend tailoring local guidelines to reflect the diverse cultural and religious perspectives of the populations they govern. Ethics models should be adapted to local populations to effectively establish research protections, growth, and possibilities of stem cell research.

For example, in countries with strong beliefs in the moral sanctity of embryos or heavy religious restrictions, an adaptive model can allow for discussion instead of immediate rejection. In countries with limited individual rights and voice in science policy, an adaptive model ensures cultural, moral, and religious views are taken into consideration, thereby building social inclusion. While this ethical consideration by the government may not give a complete voice to every individual, it will help balance policies and maintain the diverse perspectives of those it affects. Embracing an adaptive ethics model of ESC research promotes open-minded dialogue and respect for the importance of human belief and tradition. By actively engaging with cultural and religious values, researchers can better handle disagreements and promote ethical research practices that benefit each society.

This brief exploration of the religious and cultural differences that impact ESC research reveals the nuances of relative ethics and highlights a need for local policymakers to apply a more intense adaptive model.

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Culturally, autonomy practices follow a relational autonomy approach based on a paternalistic deontological health care model. The adherence to strict international research policies and religious pillars within the regulatory environment is a great foundation for research ethics. However, there is a need to develop locally targeted ethics approaches for research (as called for in Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6), this decision-making approach may help advise a research decision model. For more on the clinical cultural autonomy approaches, see: Alabdullah, Y. Y., Alzaid, E., Alsaad, S., Alamri, T., Alolayan, S. W., Bah, S., & Aljoudi, A. S. (2022). Autonomy and paternalism in Shared decision‐making in a Saudi Arabian tertiary hospital: A cross‐sectional study. Developing World Bioethics , 23 (3), 260–268. https://doi.org/10.1111/dewb.12355 ; Bukhari, A. A. (2017). Universal Principles of Bioethics and Patient Rights in Saudi Arabia (Doctoral dissertation, Duquesne University). https://dsc.duq.edu/etd/124; Ladha, S., Nakshawani, S. A., Alzaidy, A., & Tarab, B. (2023, October 26). Islam and Bioethics: What We All Need to Know . Columbia University School of Professional Studies. https://sps.columbia.edu/events/islam-and-bioethics-what-we-all-need-know

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[41] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a

[42] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a

[43] The EU’s definition of autonomy relates to the capacity for creating ideas, moral insight, decisions, and actions without constraint, personal responsibility, and informed consent. However, the EU views autonomy as not completely able to protect individuals and depends on other principles, such as dignity, which “expresses the intrinsic worth and fundamental equality of all human beings.” Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3

[44] Council of Europe. Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS No. 164) https://www.coe.int/en/web/conventions/full-list?module=treaty-detail&treatynum=164 (forbidding the creation of embryos for research purposes only, and suggests embryos in vitro have protections.); Also see Drabiak-Syed B. K. (2013). New President, New Human Embryonic Stem Cell Research Policy: Comparative International Perspectives and Embryonic Stem Cell Research Laws in France. Biotechnology Law Report , 32 (6), 349–356. https://doi.org/10.1089/blr.2013.9865

[45] Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3

[46] Tomuschat, C., Currie, D. P., Kommers, D. P., & Kerr, R. (Trans.). (1949, May 23). Basic law for the Federal Republic of Germany. https://www.btg-bestellservice.de/pdf/80201000.pdf

[47] Regulation of Stem Cell Research in Germany . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-germany

[48] Regulation of Stem Cell Research in Finland . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-finland

[49] Regulation of Stem Cell Research in Spain . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-spain

[50] Some sources to consider regarding ethics models or regulatory oversights of other cultures not covered:

Kara MA. Applicability of the principle of respect for autonomy: the perspective of Turkey. J Med Ethics. 2007 Nov;33(11):627-30. doi: 10.1136/jme.2006.017400. PMID: 17971462; PMCID: PMC2598110.

Ugarte, O. N., & Acioly, M. A. (2014). The principle of autonomy in Brazil: one needs to discuss it ... Revista do Colegio Brasileiro de Cirurgioes , 41 (5), 374–377. https://doi.org/10.1590/0100-69912014005013

Bharadwaj, A., & Glasner, P. E. (2012). Local cells, global science: The rise of embryonic stem cell research in India . Routledge.

For further research on specific European countries regarding ethical and regulatory framework, we recommend this database: Regulation of Stem Cell Research in Europe . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-europe

[51] Klitzman, R. (2006). Complications of culture in obtaining informed consent. The American Journal of Bioethics, 6(1), 20–21. https://doi.org/10.1080/15265160500394671 see also: Ekmekci, P. E., & Arda, B. (2017). Interculturalism and Informed Consent: Respecting Cultural Differences without Breaching Human Rights. Cultura (Iasi, Romania) , 14 (2), 159–172.; For why trust is important in research, see also: Gray, B., Hilder, J., Macdonald, L., Tester, R., Dowell, A., & Stubbe, M. (2017). Are research ethics guidelines culturally competent? Research Ethics , 13 (1), 23-41. https://doi.org/10.1177/1747016116650235

[52] The Qur'an (M. Khattab, Trans.). (1965). Al-Mu’minun, 23: 12-14. https://quran.com/23

[53] Lenfest, Y. (2017, December 8). Islam and the beginning of human life . Bill of Health. https://blog.petrieflom.law.harvard.edu/2017/12/08/islam-and-the-beginning-of-human-life/

[54] Aksoy, S. (2005). Making regulations and drawing up legislation in Islamic countries under conditions of uncertainty, with special reference to embryonic stem cell research. Journal of Medical Ethics , 31: 399-403.; see also: Mahmoud, Azza. "Islamic Bioethics: National Regulations and Guidelines of Human Stem Cell Research in the Muslim World." Master's thesis, Chapman University, 2022. https://doi.org/10.36837/ chapman.000386

[55] Rashid, R. (2022). When does Ensoulment occur in the Human Foetus. Journal of the British Islamic Medical Association , 12 (4). ISSN 2634 8071. https://www.jbima.com/wp-content/uploads/2023/01/2-Ethics-3_-Ensoulment_Rafaqat.pdf.

[56] Sivaraman, M. & Noor, S. (2017). Ethics of embryonic stem cell research according to Buddhist, Hindu, Catholic, and Islamic religions: perspective from Malaysia. Asian Biomedicine,8(1) 43-52. https://doi.org/10.5372/1905-7415.0801.260

[57] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[58] Lecso, P. A. (1991). The Bodhisattva Ideal and Organ Transplantation. Journal of Religion and Health , 30 (1), 35–41. http://www.jstor.org/stable/27510629 ; Bodhisattva, S. (n.d.). The Key of Becoming a Bodhisattva . A Guide to the Bodhisattva Way of Life. http://www.buddhism.org/Sutras/2/BodhisattvaWay.htm

[59] There is no explicit religious reference to when life begins or how to conduct research that interacts with the concept of life. However, these are relevant verses pertaining to how the fetus is viewed. (( King James Bible . (1999). Oxford University Press. (original work published 1769))

Jerimiah 1: 5 “Before I formed thee in the belly I knew thee; and before thou camest forth out of the womb I sanctified thee…”

In prophet Jerimiah’s insight, God set him apart as a person known before childbirth, a theme carried within the Psalm of David.

Psalm 139: 13-14 “…Thou hast covered me in my mother's womb. I will praise thee; for I am fearfully and wonderfully made…”

These verses demonstrate David’s respect for God as an entity that would know of all man’s thoughts and doings even before birth.

[60] It should be noted that abortion is not supported as well.

[61] The Vatican. (1987, February 22). Instruction on Respect for Human Life in Its Origin and on the Dignity of Procreation Replies to Certain Questions of the Day . Congregation For the Doctrine of the Faith. https://www.vatican.va/roman_curia/congregations/cfaith/documents/rc_con_cfaith_doc_19870222_respect-for-human-life_en.html

[62] The Vatican. (2000, August 25). Declaration On the Production and the Scientific and Therapeutic Use of Human Embryonic Stem Cells . Pontifical Academy for Life. https://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20000824_cellule-staminali_en.html ; Ohara, N. (2003). Ethical Consideration of Experimentation Using Living Human Embryos: The Catholic Church’s Position on Human Embryonic Stem Cell Research and Human Cloning. Department of Obstetrics and Gynecology . Retrieved from https://article.imrpress.com/journal/CEOG/30/2-3/pii/2003018/77-81.pdf.

[63] Smith, G. A. (2022, May 23). Like Americans overall, Catholics vary in their abortion views, with regular mass attenders most opposed . Pew Research Center. https://www.pewresearch.org/short-reads/2022/05/23/like-americans-overall-catholics-vary-in-their-abortion-views-with-regular-mass-attenders-most-opposed/

[64] Rosner, F., & Reichman, E. (2002). Embryonic stem cell research in Jewish law. Journal of halacha and contemporary society , (43), 49–68.; Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[65] Schenker J. G. (2008). The beginning of human life: status of embryo. Perspectives in Halakha (Jewish Religious Law). Journal of assisted reproduction and genetics , 25 (6), 271–276. https://doi.org/10.1007/s10815-008-9221-6

[66] Ruttenberg, D. (2020, May 5). The Torah of Abortion Justice (annotated source sheet) . Sefaria. https://www.sefaria.org/sheets/234926.7?lang=bi&with=all&lang2=en

[67] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[68] Gert, B. (2007). Common morality: Deciding what to do . Oxford Univ. Press.

[69] World Medical Association (2013). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA , 310(20), 2191–2194. https://doi.org/10.1001/jama.2013.281053 Declaration of Helsinki – WMA – The World Medical Association .; see also: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1979). The Belmont report: Ethical principles and guidelines for the protection of human subjects of research . U.S. Department of Health and Human Services. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html

[70] Zakarin Safier, L., Gumer, A., Kline, M., Egli, D., & Sauer, M. V. (2018). Compensating human subjects providing oocytes for stem cell research: 9-year experience and outcomes. Journal of assisted reproduction and genetics , 35 (7), 1219–1225. https://doi.org/10.1007/s10815-018-1171-z https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063839/ see also: Riordan, N. H., & Paz Rodríguez, J. (2021). Addressing concerns regarding associated costs, transparency, and integrity of research in recent stem cell trial. Stem Cells Translational Medicine , 10 (12), 1715–1716. https://doi.org/10.1002/sctm.21-0234

[71] Klitzman, R., & Sauer, M. V. (2009). Payment of egg donors in stem cell research in the USA. Reproductive biomedicine online , 18 (5), 603–608. https://doi.org/10.1016/s1472-6483(10)60002-8

[72] Krosin, M. T., Klitzman, R., Levin, B., Cheng, J., & Ranney, M. L. (2006). Problems in comprehension of informed consent in rural and peri-urban Mali, West Africa. Clinical trials (London, England) , 3 (3), 306–313. https://doi.org/10.1191/1740774506cn150oa

[73] Veatch, Robert M. Hippocratic, Religious, and Secular Medical Ethics: The Points of Conflict . Georgetown University Press, 2012.

[74] Msoroka, M. S., & Amundsen, D. (2018). One size fits not quite all: Universal research ethics with diversity. Research Ethics , 14 (3), 1-17. https://doi.org/10.1177/1747016117739939

[75] Pirzada, N. (2022). The Expansion of Turkey’s Medical Tourism Industry. Voices in Bioethics , 8 . https://doi.org/10.52214/vib.v8i.9894

[76] Stem Cell Tourism: False Hope for Real Money . Harvard Stem Cell Institute (HSCI). (2023). https://hsci.harvard.edu/stem-cell-tourism , See also: Bissassar, M. (2017). Transnational Stem Cell Tourism: An ethical analysis. Voices in Bioethics , 3 . https://doi.org/10.7916/vib.v3i.6027

[77] Song, P. (2011) The proliferation of stem cell therapies in post-Mao China: problematizing ethical regulation, New Genetics and Society , 30:2, 141-153, DOI: 10.1080/14636778.2011.574375

[78] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a

[79] International Society for Stem Cell Research. (2024). Standards in stem cell research . International Society for Stem Cell Research. https://www.isscr.org/guidelines/5-standards-in-stem-cell-research

[80] Benjamin, R. (2013). People’s science bodies and rights on the Stem Cell Frontier . Stanford University Press.

Mifrah Hayath

SM Candidate Harvard Medical School, MS Biotechnology Johns Hopkins University

Olivia Bowers

MS Bioethics Columbia University (Disclosure: affiliated with Voices in Bioethics)

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This work is licensed under a Creative Commons Attribution 4.0 International License .

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