October 2019 – Lab on a Chip Blog

Archive for October, 2019

Emerging Investigators Series – Ye Ai

22 Oct 2019

Dr. Ye Ai is currently an Associate Professor at Singapore University of Technology and Design (SUTD). He obtained his B.S. in Mechanical Engineering from Huazhong University of Science and Technology (China) in 2005 and his Ph.D. in Mechanical and Aerospace Engineering from Old Dominion University (USA) in 2011. Prior to joining SUTD as an assistant professor in 2013, he worked as a postdoctoral researcher at the Bioscience Division of Los Alamos National Laboratory from June 2011 to January 2013. He was a visiting scholar at Massachusetts Institute of Technology (MIT) from August 2014 to July 2015. He was promoted to associate professor with tenure in September 2019. Dr. Ai’s research interest focuses on developing novel microfluidic technologies for particle/cell manipulation and single cell analysis. His research team is also striving to translate their innovative microfluidic technologies to commercial market through collaborations with industry.

Read Dr Ai’s recent Emerging Investigator Series paper: Microfluidic impedance cytometry device with N-shaped electrodes for lateral position measurement of single cells/particles in the most recent issue of Lab on a Chip, and find out more about him and his work below.

Your recent Emerging Investigator Series paper focuses on measuring the lateral position of single cells or particles. How has your research evolved from your first article to this most recent article?

My first research article when I was a PhD student was to develop a finite element model with dynamically deformed mesh that can simulate the transient motion of finite-size particles in microscale fluid flows. My PhD research mainly focused on electrokinetics for manipulating particles, cells and ions in micro/nanoscale. My postdoctoral training at the Bioscience Division of Los Alamos National Laboratory exposed me to a lot of biological problems, in particular the need in high-throughput cellular analysis at the single cell level. My previous research experience has somehow shaped my current research focus into single cell manipulation and analysis using novel microfluidic technologies when I become an independent principal investigator in Singapore.

What aspect of your work are you most excited about at the moment?

I am most excited to apply our developed microfluidic technologies for solving real biomedical problems and enabling new biological studies. As an example, in 2017 my team published our single cell sorting technology using a highly focused acoustic beam in Lab Chip (DOI: 10.1039/c7lc00678k). Later, I was approached by quite a number of research teams worldwide who wanted to try our sorting technology. These email communications have encouraged me to apply our developed prototype for real biomedical problems. Right now, I have established collaboration with a few biomedical research institutes in Singapore and we have found that our sorting technology is not causing any cell damage, which is however challenging for conventional FACS machine. We currently have the idea to commercialize this single cell sorting technology. Let us see what is going to happen in the next few years.

In your opinion, what are the key considerations when designing a microfluidic platform for real-time measurements?

My research team is currently developing both hydrodynamic and acoustic cell sorting platforms. The conventional way to quantify the sorting performance (e.g. purity and recovery) is to run additional cell analysis of collected samples, typically using a flow cytometer. In this work (DOI: 10.1039/c9lc00819e), we designed and validated a new impedance cytometry device that enables the measurement of the lateral positions and physical properties of individual particles and cells. The integration of this new device with any cell sorting platform will allow the evaluation of the sorting performance to be implemented in the same system.

The key consideration of integrating these real-time measurements really depends on whether there is a critical need. But I do see a lot of sorting applications need these real-time, in-line measurements for the purposes of quality control and workflow simplification. And any integration will somehow complicate the system and increase the cost, so the other key consideration is the ease of integration. Integration of electronics is generally easier compared to optics, and we are measuring intrinsic biophysical properties rather than labelling approaches; therefore, I do see great opportunities to integrate our new impedance cytometry device with a variety of cell sorting platforms.

What do you find most challenging about your research?

The microfluidics and Lab on a chip research area is interdisciplinary in nature. My challenge is always to find the right people (e.g. students, postdoctoral fellows, collaborators) and secure sufficient resources to work on real impactful research problems.

How do you spend your spare time?

I am trying to make a balance between work and personal life, so I mainly spend my spare time with my family members, especially my second kid is only 8 months old. I also spend some of my spare time to do physical exercise, which can help relax and leave some time for free thinking.

Which profession would you choose if you were not a scientist?

I rarely thought about this before. Perhaps I would choose to be a doctor.

Can you share one piece of career-related advice or wisdom with other early career scientists?

Based on my own experience, it is important to define a unique research domain based on your own expertise and the surrounding research ecosystem when early career scientists start their independent research. It is also wise to have a clear vision about what you want to achieve in the next five years.

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New thematic collection open for submissions – Single Cell Analysis

16 Oct 2019

We are delighted to announce a new thematic collection in Lab on a Chip, focusing on multimodal single cell analysis, with Professors Daniel T. Chiu and Pratip K. Chattopadhyay as thought leaders.

Professors Chiu and Chattopadhyay describe the current challenges in the field in their recent editorial in Lab on a Chip on “The Next Frontier in Single Cell Analysis: MultiModal Studies and Clinical Translation”:

“Biological processes are inherently complex. Stochasticity, redundancy, plasticity, and noise are built into fundamental cellular activities from gene transcription to protein expression. A major challenge in biomedical research is to untangle this complexity. Microarray technology influenced biological research because it demonstrated clearly the wide selection of cellular molecules available for measurement and provided an efficient means to query them. However, microarrays require a large amount of material and assay large numbers of cells together in bulk.

Single cell analysis overcomes the problems of bulk measurements, but for many years the only available technology—flow cytometry—was incapable of highly multiplexed measurements. The current movement in single cell analysis is multimodal characterization. These approaches, which are rapidly replacing one-dimensional single cell analysis in biomedical research, simultaneously combine measurements of transcription with post-transcriptional regulation, epigenetic modifications, and surface protein expression. It is possible that lipid and metabolite composition, and/or cellular morphology may also be analyzed with the transcriptome or proteome.

We now have a dizzying array of tools that provide us with the potential to comprehensively and accurately characterize the cells involved in a biological process. We are a step away from using these tools widely and efficiently to impact clinical care, but there are large obstacles we must break down first. With a better understanding of the complexity ingrained in cellular systems, how do we smartly choose subsets of markers and cell types to survey, remembering that samples from patients are often limited as are research budgets? Once we know what to measure, there is the critical question of how to measure it, since there are a myriad of technical platforms and data analysis tools from which to choose. As we make measurements, how do we ensure that they are robust—are there general validation and quality control principles we can establish, or are such measures wholly platform-specific? Finally, are highly multiplexed, single cell technologies valuable only as a screening tool to identify simple biomarkers, or can these highly complex technologies (and their associated data analysis algorithms) be used directly for clinical diagnostics?”

We invite review and research manuscripts that suggest answers to these questions and related issues for inclusion in a thematic collection focused on multimodal single cell analysis. If you are interested in submitting to the collection please contact the Editorial Office.

This collection open for submissions now, and into 2020.

If you’re interested in this topic, you can read our previous thematic collection on droplet-based single-cell sequencing here. The articles are free to read until November 15^th 2019.

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What are the challenges to sample-in-answer-out technologies in clinical settings?

09 Oct 2019

The boom in microfluidic total analysis systems is spurred by the use of microscale fabrication techniques. In 1999, Agilent Technologies introduced a coin-size device called “LabChip” to the market for the analysis of DNA. The timing of the market release of this device was remarkable as it benefited from the hype of the Human Genome Project. The LabChip has drawn considerable attention from both academia and industry. As a result, the shrink of chemistry labs into coin-sized microfluidic devices has evolved more from technological push than from market pull. Technology-driven development pathway brought challenges, especially for the clinical integration of microfluidic devices due to the lack of standards, focus, and communication between academia and clinics.

A recent Lab on a Chip paper from Martyn Boutelle’s Lab addresses this issue. The authors identify the problem from a well-addressed microdialysis perspective. They state that “taking a microfluidic system into clinical environment brings lots of challenges, not least that during setups and developments the very low the flow rates used in combination with microdialysis means that leaks and misdirection of flows are very hard to see.” The authors define the most significant challenge as the development of a device that’s robust enough to be used by and provide enough information to, the clinical team without micromanagement by experts.

The authors attack the problem by creating a sensor-based online system associated with electrochemical measurement, which would be able to analyze the sample in a miniaturized platform continuously. They developed the microfluidic sensors and chip, but they wanted to increase the use of their technology in real-world scenarios by non-experts, so they looked into ways to introduce more precision and control to the platform. The authors combined their technology with LabSmith microfluidic components and constructed breadboard like layouts for typical lab protocols. The authors add that “the main surprise was the ability to bring the rigor of an analytical laboratory into unusual places such as abattoirs, surgical theatres and public transport!”

In this work and the previous work of the authors, the performance of 3-D printed chips was compared to the PDMS ones. The authors found that PDMS material is much more vulnerable than the 3D print outs when frequently handled. The sensor attached to the chip is programmed to calibrate in regular intervals (e.g., every three hours) in single or multiphase flow conditions. Authors describe the advantage of the system that ”remote access to the scripts allows interaction with the system without the requirement of a highly skilled person being right next to it, which in the context of surgical theatres and hospital wards is a distinct advantage. If the codes and scripts are available to less skilled personnel, they are still able to interact and use the system and by making the system more user-friendly a wider audience and more enthusiasm is generated for the product, increasing interest, uptake, and use.”

The authors would like to improve the platform further by making it wearable since it already has grounds for such an operation with wireless sensors. The next thing to be improved in the system is the feed. At this moment, the syringes have to be regularly refilled. This might not be a problem in the laboratory; however, monitoring can last for days in a clinical setting, and periodically refilling the syringes may lead to noise artifacts. Another improvement could be the ease of operation and troubleshooting when, e.g., a tubing becomes blocked in the middle of the measurement when the user is short on space and time.

Lastly, the authors think that this pioneering platform can help shape the future in the market by giving more people access to an area of science that was previously highly skilled, whilst maintaining analytical robustness. This will be the start to break the barrier between academia-made devices and clinical settings.

To download the full article for free* click the link below:

Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness

Sally A. N. Gowers, Michelle L. Rogers, Marsilea A. Booth, Chi L. Leong, Isabelle C. Samper, Tonghathai Phairatana, Sharon L. Jewell, Clemens Pahl, Anthony J. Strong and Martyn G. Boutelle, Lab Chip, 2019, Lab on a Chip Hot Articles

DOI: 10.1039/C9LC00400A

*access is free with an RSC account (free to register)

About the Webwriter

Burcu Gumuscu is a researcher in Mesoscale Chemical Systems Group at the University of Twente in the Netherlands. Her research interests include the development of microfluidic devices for quantitative analysis of proteins from single-cells, next-generation sequencing, compartmentalized organ-on-chip studies, and desalination of water on the microscale.

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Emerging Investigators Series – Jacqueline Linnes

01 Oct 2019

Dr. Jacqueline Linnes is an Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. She received her B.S. in Engineering from the Purdue University and Ph.D. in Biongineering from the University of Washington. She was a Fogarty Postdoctoral Fellow at the Division of Global Health Equity within Brigham and Women’s Hospital/Harvard Medical School and continued her postdoctoral training at Boston University in Biomedical Engineering. She has received numerous awards including the Mandela Fellows Global Innovation Challenge Award (2017), Fast Company’s World Changing Ideas Finalist (2018), and Marta E. Gross Assistant Professorship of Biomedical Engineering (2018).

Dr. Linnes’s research lab develops real-time detection technologies to prevent, diagnose, and better understand the pathogenesis of diseases. This work emphasizes the translation of fundamental microfluidics and biological assays into point-of-care diagnostics using human-centered design principles. Her extensive experience in translational research includes co-founding and managing early-stage field-testing and user feedback for two startup companies. She has co-developed point-of-care health diagnostics, wearable devices, and water purification technologies for use in the US, Bolivia, Nicaragua, Kenya, Zambia, and Haiti.

Read Dr Linnes’s Emerging Investigator article “Microfluidic Rapid and Autonomous Analytical Device (microRAAD) to Detect HIV from Whole Blood Samples” and find out more about her in the interview below.

Your recent Emerging Investigator Series paper focuses on detecting HIV using a microRAAD. How has your research evolved from your first article to this most recent article?

As a PhD student, I published on the causes of bacterial adhesion to proteins adsorbed to medical devices (in 2012). These infections are incredibly difficult to detect and I found that I didn’t want to just study the causes of infections but to develop the diagnostic tools themselves. I now use the molecular biology and surface analysis skills that I developed in my PhD to create point-of-care diagnostic devices in my own lab. A critical shift in my thinking came when I realized that both the technical skills and the problem solving mindset that I learned in my PhD research were transferable to entirely different fields. In my two postdocs, I worked on Global Health projects ranging from infection control to point-of-care diagnostic devices. Now in my own research lab, we focus on developing, integrating and automating real-time detection technologies including point-of-care diagnostics and wearable devices, to meet the needs of underserved populations. This article is an example of a sample-to-answer test we developed to automate molecular detection of a pathogen (HIV) from whole blood sample at the point-of-care.

What aspect of your work are you most excited about at the moment?

I started my lab in 2015 with the vision that we could automate molecular detection in point-of-care diagnostics, so that the dvices could be used by anyone, anywhere in the world. I love that we have pulled together individuals with expertise in so many different fields from materials science, to electrical engineering, to molecular biology in order to make this technology work. A huge contingent of my lab and Dr. Stanciu’s lab, and at all levels, from undergraduate researchers to PhD’s have contributed to this project. Now we are bringing in more expertise in translational clinical research. I am currently in Kenya and just handed over a batch of these microRAADs to my colleague, Dr. Eddy Odari at Jomo Kenyatta University of Agriculture and Technology. Dr. Odari will be testing the MicroRAADs using real patient samples and I can’t wait to find out the results.

In your opinion, what is the biggest advantage to using your microRAAD compared to other methods of detecting HIV?

I know there’s still a ways to go, but I believe that the microRAAD platform will ultimately bridge the gap between laboratory-based molecular detection instruments and truly point-of-care diagnosis of HIV in the field.

What do you find most challenging about your research?

Designing technologies sample-to-answer molecular diagnostics that are both highly sensitive and remain robust and accessible to the clinicians, technicians, and patients who need them is incredibly challenging. In my lab, we find it critical to test out our ideas and prototypes via formal and informal usability studies to understand what can be done practically in the field settings that they are designed for. We redesign anything that isn’t actually usable in the real world.

At which upcoming conferences or events may our readers meet you?

I am at the 4th Africa International Biotechnology and Biomedical Conference in Nairobi and Mombasa, Kenya, and this October I will be attending the 2019 Biomedical Engineering Society Annual Meeting in Philadelphia, USA, and the 2019 MicroTAS conference in Basel, Switzerland.

How do you spend your spare time?

I have a 5 year old and a 3 year old so “spare time” is perhaps an overstatement, but we spend a lot of time outdoors at parks and playgrounds and my husband and I built a tree house in our backyard this summer.

Which profession would you choose if you were not a scientist?

That’s a tough one. I love my job as a biomedical engineering faculty member. I do think it would be fantastic to work at a science museum developing and building exhibits and outreach activities.

Can you share one piece of career-related advice or wisdom with other early career scientists?

Don’t underestimate the power that people play in your research. Play well with others, find a place that supports you in your efforts, seek out excellent employees and mentees, and make sure to invest in their development and in your own. Whenever possible, work directly with the people that you ultimately want to use your technology. It is both incredibly motivating and absolutely critical to making an impact that reaches beyond the confines of your own lab.

Dr Jacqueline Linnes (Picture credit: Purdue University photo/Rebecca Wilcox)

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Lab on a Chip Blog

Archive for October, 2019

Emerging Investigators Series – Ye Ai

New thematic collection open for submissions – Single Cell Analysis

What are the challenges to sample-in-answer-out technologies in clinical settings?

Emerging Investigators Series – Jacqueline Linnes

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