Pioneers of Miniaturization Lectureship 2018

We are delighted to announce that Sunghoon Kwon is 2018 winner of the “Pioneers of Miniaturization” Lectureship!

The 13th “Pioneers of Miniaturization” Lectureship, sponsored by Dolomite and Lab on a Chip , is for early to mid-career scientists who have made extraordinary or outstanding contributions to the understanding or development of miniaturised systems.

This “Pioneers of Miniaturization” Lectureship will be presented to Sunghoon at the µTAS 2018 Conference in Kaohsiung, Taiwan, being held on 11-15 November, 2018. Sunghoon will receive a certificate, a monetary award and will give a short lecture during the conference.

Many congratulations to Professor Sunghoon Kwon on this achievement from the Lab on a Chip Team!

 

About the Winner

©Youngkwang Kang

Sunghoon Kwon earned his PhD in Bioengineering from University California at Berkeley, California, USA  in 2004. After a postdoctoral fellowship at Lawrence Berkeley National Laboratory, he was appointed to his current role as a Professor at the Department of Electrical Engineering at Seoul National University.

In recognition of his outstanding achievements, Dr. Kwon has received numerous awards, including Young Scientist Award from The Korean Academy of Science and Technology (2011), Young Scientist Award from the Korean President (2012), “IT Young Engineer Award” from IEEE (2016), Young Engineer Award from National Academy of Engineering of Korea (2018). He has authored more than 70 peer-reviewed publications and has served as Advisory Board member of Lab on a Chip since 2017. Another major contribution by Professor Kwon is the commercialization of his microfluidic technologies. A rapid antibiotic susceptibility testing method published in Lab on a Chip (2013) and Science Translational Medicine (2014) and a high-throughput DNA synthesis method (Nature Communications 2015) has been commercialized by two companies, which were spun off Professor Kwon’s laboratory.

His research interests are the interface of biomedical engineering, bioMEMS, optofluidics, nanofabrication, and nanoengineering, specifically focusing on innovative diagnostic and synthetic biology platforms for personalized medicine.

Learn about the Kwon group online

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2018 Art in Science Competition

Get your entries in before the deadline on 15th October 2018 (23:59 Honolulu, Hawaii, USA time)

 

The µTAS 2018 Conference will feature the 11th Art in Science competition entitled ‘Under the Looking Glass: Art from the World of Small Science‘, sponsored and supported by National Institute of Standards and TechnologyLab on a ChipMicroTAS and the Chemical and Biological Microsystems Society.

Since the earliest publications of the scientific world, the aesthetic value of scientific illustrations and images has been critical to many researchers. The illustrations and diagrams of earlier scientists such as Galileo and Da Vinci have become iconic symbols of science and the scientific thought process.

In current scientific literature, many scientists consider the selection of a publication as a “cover article” in a prestigious journal to be very complimentary.

Deadline 15th October 2018 at 23:59 Honolulu, Hawaii, USA time—please note this is a month before the conference!

 

Are you attending the µTAS 2018 Conference?

Would you like your image to be featured on the cover of Lab on a Chip?

To draw attention to the aesthetic value in scientific illustration while still conveying scientific merit, NIST, LOC and CBMS are sponsoring this annual competition. Applications are encouraged from authors in attendance of the µTAS Conference and the winner will be selected by a panel of judges and presented at the Royal Society of Chemistry/Lab on a Chip booth during the last poster session of the 2018 MicroTAS conference.

Applications must show a photograph, micrograph or other accurate representation of a system that would be of interest to the µTAS community and be represented in the final manuscript or presentation given at the Conference.

They must also contain a brief caption that describes the illustration’s content and its scientific merit. The winner will be selected on the basis of aesthetic eye appeal, artistic allure and scientific merit. In addition to having the image featured on the cover of Lab on a Chip, the winner will also receive a financial prize at the Conference.


Art in Science Competition Submission Process

Step 1. Sign-In to the Electronic Form Using Your Abstract/Manuscript Number

Step 2. Fill in Remaining Information on Electronic Submission Form

Step 3. Upload Your Image

Good Luck!

You can also take a look at the winners from last year on our blog.

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Emerging Investigator Series: Kiana Aran

Dr. Aran received her undergraduate degree in electrical engineering at the City University of New York in 2007 and her Ph.D in biomedical engineering at Rutgers University in 2012. She then continued her postdoctoral studies in bioengineering at the University of California Berkeley and was a recipient of National Institutes of Health (NIH) postdoctoral training fellowship at the Buck Institute for Age Research in 2015. She joined Keck Graduate Institute in 2017 as an Assistant Professor and is a currently a visiting scientist at the University of California Berkeley. She is also a consultant for Bill and Melinda Gate Foundation and cofounder of NanoSens innovations. Since starting her faculty position in 2017, Dr. Aran work has been supported by various funds including one RO1, industry sponsored research and a 3 years subaward from University of California Berkeley.

Read her Emerging Investigator Series article “Graphene-based biosensor for on-chip detection of Bio-orthogonally Labeled Proteins to Identify the Circulating Biomarkers of Aging during Heterochronic Parabiosis” and find out more about her in the interview below:

 

Your recent Emerging Investigator Series paper focuses on Digital Detection of tagged proteins in vivo to identify the circulating biomarkers in aging. How has your research evolved from your first article to this most recent article?

I was a recipient of an NIH T32 award during my last years of postdoc training at UC Berkeley (2015-2017) which provided me with the opportunity to work with Dr. Irina Conboy, a pioneer in utilizing bio-orthogonally labeled proteins for research on aging. This approach enabled the detection of several rejuvenating protein candidates from the young parabiont, which were transferred to the old mammalian tissue through their shared circulation. Although this method was very powerful, there were a lot of challenges with the detection of these tagged proteins including very time consuming, complex and expensive assays, large sample requirement and false positive. I started working on this project as a side project along with other projects I had with Dr. Conboy just to make the process more facile so we can detect these protein faster and more continuously. This work is a great example of utilizing a lab on a chip technology for a real application. I have also started collaboration with nanomedical diagnostics, a startup company in San Diego, to enable mass production of our chips with high reproducibility. With my academic and industrial collaborators, we are planning to utilize this technology for at least two different applications in the near future to better understand the biology of aging.

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

I am very excited to see my technologies go beyond publications. Two of my inventions have been licensed toward developing medical devices for drug delivery and medical diagnostics and the joy from that have been the biggest drive for me to work harder.

In your opinion, what is the future of portable devices for biosensing?

Even though still in its emerging stage, digital diagnostics and 2D materials will shape the future of biosensors.

What do you find most challenging about your research?

As a junior faculty, it is difficult to recruit highly motivated postdoctoral researchers. Unfortunately, the majority of postdoctoral candidates often look for a well-established laboratory headed by a leading scientist. Students and postdoc should know that working in a new lab can be challenging but can provide researcher with opportunities to strengthen their scientific and management skills.

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

I will be presenting some of my biosensor work in the upcoming IEEE EMBS MNMC Conference

Above: Dr Aran supports a community in Africa by building a school

How do you spend your spare time? 

I love what I do so I can not define my spare time from my work time. I have recently co-founded a startup in digital diagnostics so that takes my weekend but I love it. I also paint when I feel like painting.  But I do run, swim and work out routinely after work and enjoy a variety of sports.  I have also started traveling to small villages around the world with my friends where we help in building schools.

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

I love painting and would have explored a career in art.

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

Have a vision. Sometimes we get lost in small career goals such as publishing but if you have a vision of what you are trying to accomplish you can define your career path, you will start working with the right people who support your vision, you will attend the right conferences and workshops for your career development and you will definitely be successful.

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Emerging Investigator Series: Adriana San Miguel

Adriana San Miguel is an Assistant Professor in the Department of Chemical & Biomolecular Engineering at NC State University. She is part of the Synthetic and Systems Biology Chancellor´s Faculty Excellence Program. Her work combines engineering and biology and focuses on developing tools to perform high-throughput automated experiments with the model organism C. elegans. Her team uses these tools and this organism to better understand aging, stress, and the nervous system.

Adriana is originally from San Luis Potosi, Mexico. After receiving a BS in Chemical Engineering at the Monterrey Institute of Technology (ITESM) in 2005, she worked in the water treatment and cement industries for 2 years. She obtained a Ph.D. in Chemical Engineering from the Georgia Institute of Technology in 2011. She then took on a Postdoctoral Research position at Georgia Tech, and a second one at the Dana-Farber Cancer Institute in Boston. In 2013, Adriana was awarded the NIH K99 Pathway to Independence Award to study the mechanisms regulating synaptic plasticity and aging in the nematode C. elegans.

Read her Emerging Investigator Series article “A microfluidic platform for lifelong high-resolution and high throughput imaging of subtle aging phenotypes in C. elegansand find out more about her in the interview below:

Your recent Emerging Investigator Series paper focuses on a microfluidic platform for high-resolution and high throughput imaging of aging phenotypes in C. elegans. How has your research evolved from your first article to this most recent article? 

We have previously been interested in developing systems for high-throughput imaging and analysis of subcellular features in C. elegans, and gained interest in quantitatively assessing how these change during aging. Aging studies pose several technical challenges that could not be addressed with previous microfluidic devices, thus our interest in developing a system capable of performing high-throughput analysis of aging phenotypes.

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

I am excited about the possibility of doing systems biology enabled by microfluidics. Lab on chip approaches provide an excellent level of precision in experimental conditions which are unfeasible with traditional C. elegans techniques. Microfluidics also allows high-throughput studies that result in large data sets, and as a consequence, a need to perform unsupervised quantitative data analysis. When combined, these powerful approaches enable better understanding of biological processes from a systems perspective.

In your opinion, what are the challenges with using microfluidics for whole organism behaviour?

Behavioral studies are challenging, particularly because there is a large degree of variability within a population. Microfluidics can help by facilitating animal handling and ensuring the stimuli used is precise (in time, concentration, and localization). Although it is difficult to determine how representative a microfluidic environment (where animals navigate in 2D) resembles their natural 3D environment, microfluidic chips enable single animal tracking, thus increasing the confidence of noisy behavioral readouts.

What do you find most challenging about your research?

Our research requires the integration of several different fields. We develop microfluidic tools, and use them to answer fundamental biological questions. In addition, we use automation, image processing, machine learning, and analysis tools for the large data sets we acquire. Integrating all of these can certainly be challenging, but achieving fully integrated systems is what we find very motivating.

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

I typically attend the American Institute of Chemical Engineers Annual Meetings, as well as the International C. elegans meeting, among others.

How do you spend your spare time?

I enjoy working out every day, it is a necessary part of my routine. I also enjoy baseball, live music, reading, and spending time with family and friends.

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

I’d probably still be an Engineer, or maybe an artist of some sort.

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

Something I could suggest is to not be afraid of testing new ideas and methods or venturing into different fields. Although it can be challenging to develop something that is completely new, if it sparks your interest, give it a try. It is very rewarding and motivating to get something new working.

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How soil-worms allow for realistic human physiology studies

Mice, fruit fly, zebra fish easily come to mind when thinking of animal models for human physiology studies – but one animal is often forgotten, although it is as functional as the others. Have you guessed already? We are talking about soil-dwelling worms, aka C. elegans! These animals combine the simplicity of single-cell systems with the complexity of animal models, therefore they can provide significant insights into human disorders. Please take a moment to look at our note below summarizing the key features of C. elegans.

Muscular strength is a good example of human physiology studies  and it relies on calcium-initiated muscle contraction, sarcomere composition and organization, and translocation of actin and myosin molecules. Analysis of such parameters can reveal the formation of muscular dystrophy, a muscle degenerative disorder. However, the measurement of these parameters has been a challenge due to the dependence on random animal-behavior that yields irreproducible results. Recently, researchers from Texas Tech University collaborated with Rutgers University and University of Nottingham to study muscular strength in C. elegans. They achieved to obtain results independent of animal behavior and gait in a miniature system consisting of an elastic micropillar forest (Figure 1a and 1b).

The microfluidic system is made of PDMS, and contains bendable micropillars hanging from the microchannel ceiling. The pillars are bent upon the action of the body muscles when C. elegans crawls through the pillar array. Individual pillar bending events can be quantified using a microscope-camera system and image analysis (Figure 1c). The pillar density is designed to create high mechanical resistance to locomotion, therefore maximum exertable force can be measured independent of animal behavior. Here, maximum exertable force corresponds to the peak force exerted by human quadriceps muscle in a standardized knee extension resistance test.

Figure 1. (a) Image of the microfluidic device with the pillar forest and the ports. (b) Schematic demonstration of the C. elegans strength measurement apparatus. Inset shows a scanning electron microscope picture of the pillars. (c) A sketch of interaction with a pillar by the worm body. The pillar is bent due to the action of the body muscles (shown in red and green). Image from Rahman et al.

The authors of this study explain that animals produce strong forces in highly resistive areas and demonstrate different locomotion regimes based on the body size relative to gap between pillars. Besides the body size, body configuration and behavioral characteristics can be the sources to the magnitude of the force exerted on the pillars. Thanks to the probabilistic nature of the parameters sourcing of the force exerted, a reproducible algorithm can be defined for quantifying muscle strength. Using this strategy, researchers showed for the first time that locomotion between microfluidic pillars comprises of three regimes: non-resistive (worm contacts with 1-2 pillars and doesn’t adjust body posture), moderately resistive (worm contacts with >2 pillars and minimally adjust body posture), and highly resistive (worm contacts with multiple pillars and body posture adjustment is disabled). When operated at highly-resistive regime, the microfluidic system suppresses the animal behavior. This system allows for (1) discriminating between the muscle strength or weakness levels of individual worms of different ages, (2) determining body length decrease and muscular contraction levels led by levamisole treatment, (3) comparing the muscular strength in the wild and mutant C. elegans types. According to the researchers, the future studies can help us to obtain deeper understanding in molecular and cellular circuits of neuromuscular function as well as dissection of degenerative processes in disuse, aging, and disease.

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

NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans
Mizanur Rahman, Jennifer E. Hewitt, Frank Van-Bussel, Hunter Edwards, Jerzy Blawzdziewicz, Nathaniel J. Szewczyk, Monica Driscolld, and Siva A. Vanapalli
Lab Chip, 2018, Lab on a Chip Recent Hot Articles
DOI: 10.1039/c8lc00103k

 

About the Webwriter

Burcu Gumuscu is a postdoctoral fellow in Herr Lab at UC Berkeley in the United States. Her research interests include 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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Acoustofluidics 2018

 

Acoustofluidics-18-Web-banner_date

Acoustofluidics 2018 is a three-day conference that will take place this year in Lille, France between 29th – 31st August. 

The meeting is dedicated to exploring the science, engineering, and use of micro to nanoscale acoustofluidics. The full list of invited speakers has now been confirmed and published, as well as information on registration fees and the cost of the conference dinner. Please see the conference website for details on abstract submission and how to register.

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What we know about cancer tumors

Cancer tumors are a lot more complex than we think: besides cancer cells, supportive tissue cells, fat, and even immune cells can be found in a tumor. Combined crosstalk in between these cell groups influences the way the tumor develops or responses to drug treatment. On the other hand, the majority of what we know about cancer tumors has been acquired by studying cell ensembles. Recent strides to improve our understanding of cancer revealed that we have long been missing the stochastic interactions and rare events due to ensemble-average measurements. We can unveil how these cell groups work together and how the rare events change the fate of a tumor thanks to single-cell analysis techniques.

Single cells can be identified by extrinsic and intrinsic markers. Extrinsic markers are definitive of genetic and proteomic states of a cell. Flow cytometry and mass spectrometry have been the workhorse of extrinsic marker analysis, where genetic or proteomic materials are often fluorescently labeled for detection. With these techniques, multiplexed analysis of thousands of cells can be employed simultaneously. Intrinsic markers include size, shape, density, optical, mechanical, and electrical properties which do not require labelling. Microfluidic techniques provide with a plethora of different functionalities to sort the cells based on intrinsic markers. Combination of both extrinsic and intrinsic data advances our understanding of how cell heterogeneity is reflected in cell-to-cell variations in tumor development and drug-response. Although many powerful methods are available for determining extrinsic markers, not many techniques can gather information about a panel of different intrinsic markers.

A recent study from Biological Microtechnology and BioMEMS group at MIT represents an important microfluidic approach for the development of multiparameter intrinsic cytometry tool. The approach includes several different microfluidic modules combined with microscope imaging and image processing by machine learning. Separate modules measuring cell size, deformability, and polarization can be combined and organized within the tool (Figure 1). (i) Size module detects the cell size optically in a flow through system. Cell size module is necessary to separate different cell types that can give important cues about disease state. (ii) In deformability module, cells pass through narrow channels, and their transit time defines the deformability. Cell deformability gives cues about cytoskeletal and nuclear changes associated with cancer progression. (iii) In the polarization module, dielectrophoretic force at a fixed frequency is applied on cells driven by opposing hydrodynamic forces. Cells approach coplanar electrodes with different equilibrium positions depending on their polarizability. Cell polarizability allows for distinguishing subtle changes in biological phenotypes. As a proof-of-concept work, drug-induced structural changes in cells were detected for the first time using five different intrinsic markers, including size, deformability, and polarizability at three frequencies. The authors indicate that this powerful tool can further be equipped with visual readout capabilities, such as deterministic lateral displacement array, inertial microfluidics, acoustophoresis, optical techniques.

Figure 1. Multiparameter intrinsic cytometry combines different microfluidic modules on one substrate along with cell tracking to correlate per-cell information across modules for different intrinsic properties including size, polarizability, and deformability.

 

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

Multiparameter cell-tracking intrinsic cytometry for single-cell characterization
Apichitsopa, A. Jaffe, and J. Voldman
Lab Chip, 2018, Lab on a Chip Recent Hot Articles
DOI: 10.1039/C8LC00240A

*Article free to read until 31st August 2018

About the Webwriter

Burcu Gumuscu is a postdoctoral fellow in Herr Lab at UC Berkeley in the United States. Her research interests include 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 Investigator Series – Rebecca Pompano

We are delighted to introduce our latest Lab on a Chip Emerging Investigator, Rebecca Pompano.

Dr. Rebecca Pompano is an Assistant Professor in the Departments of Chemistry and Biomedical Engineering at the University of Virginia, and a member of the Beirne B. Carter Center for Immunology Research.  She completed a BS in Chemistry at the University of Richmond in 2005, and a PhD in 2011 at the University of Chicago, working in the laboratory of Dr. Rustem Ismagilov.  She completed a postdoc in the University of Chicago Department of Surgery, leading a collaboration between Dr. Joel Collier, a tissue engineer, and Dr. Anita Chong, an immunologist.  Since 2014, she has been a faculty member at UVA, where her research interests center on developing microfluidic and chemical assays to unravel the complexity of the immune response.  She received an Individual Biomedical Research Award from The Hartwell Foundation and the national 2016 Starter Grant Award from the Society of Analytical Chemists of Pittsburgh.  Recently, her lab was awarded an NIH R01 to develop hybrids of microfluidics and lymph node tissue to study inflammation.  In addition to her research, she is active in advocating for continued funding for education and biomedical research on Capitol Hill.

Read her Emerging Investigator Series article “User-defined local stimulation of live tissue through a movable microfluidic port” and find out more about her in the interview below:

Your recent Emerging Investigator Series paper focuses on stimulation of live tissue through a movable microfluidic port. How has your research evolved from your first article to this most recent article?

My current research combines some seemingly disparate themes from my prior work.  My first article in graduate school used droplet microfluidics to study blood clotting, and I became fascinated with how spatial organization affects the function of complex biological systems. Later, I also worked on the physics of fluid flow in a reconfigurable SlipChip device… and both of these ideas make a comeback in this current paper!  Then in my postdoc, I had the fabulous opportunity to work in both a bioengineering lab and an immunology lab, studying the mechanism of action of a new non-inflammatory vaccine. The research in my lab now is really at the intersection of bioanalytical chemistry, bioengineering, and immunology.  We develop new tools to study the immune system and how it is organized. This particular paper offers a new technology to pick and choose where to deliver a drug or stimulant to a piece of live tissue, and we demonstrated it for lymph nodes, our favorite immune organ.

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

I am very excited about the ideas we are pursuing, specifically that our tools to control and detect how tissue is organized might prove useful for other researchers.  As a chemist by training, I’m thrilled to collaborate with creative bioengineers and immunologists like Jennifer Munson (Virginia Tech) and Melanie Rutkowski (U Virginia) to work on inflammatory diseases and tumor immunology.  Seeing our chips at work in their labs is very rewarding.

In your opinion, what is the biggest advantage of using local stimulation over global stimulation for measuring tissue responses?

Local stimulation, by which I mean delivering fluid or a drug to one region of tissue, rather than bathing the entire sample in media, gives you the chance to ask unique questions about spatial organization.  For example, I envision using this microfluidic technique to determine whether a drug is more effective when delivered to one area of tissue than another, and then developing a nanoparticle that targets just the right region.  It can also be used to mimic local biological events, like diffusion of signals from a blood vessel, to determine how inflammation initiates and propagates through live tissue.

What do you find most challenging about your research?

Studying the immune system – its complexity is what I love about it, but it is challenging when the cells and tissue do exactly the opposite of what you expected!  This happens over and over when we ask a real biological question. I suppose it shows how much there is still to learn, and why new tools are so desperately needed to predict and control immunity.

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

I’m looking forward to MicroTAS in Taiwan this year. I also bounce around between Pittcon (analytical chemistry), the Society for Biomaterials annual meeting, and the annual AAI Immunology conference.  This fall I’ll be attending the BMES annual meeting (Biomedical Engineering Society) for the first time!  There is not yet a focused conference for immunoanalysis and immunoengineering, but I’m hoping one will form soon.

How do you spend your spare time?

A few years ago I would have said knitting… I had a great group of friends in graduate school who would get together to knit every week.  I still wear those socks and sweaters!  Now though, my husband Drew and I spend most of our free time playing together with our 2-year old, Jasper.  Sometimes I also go to Drew’s gigs to be a rock star’s spouse instead of a chemistry professor for a while.  He’s a bassist in several great bands in Charlottesville (check a few of them out – Pale Blue Dot and 7th Grade Girl Fight).

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

I almost went into science policy instead of academia. I seriously entertained the idea of working at USAID helping promote vaccines internationally, or working in a think tank to help guide health-related policies.  I’m still very passionate about the need for scientists to inform the public and our elected officials about the science underlying issues like health, education, and care of the environment.

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

A former mentor recommended me the book, Ask For It, by Linda Babcock and Sara Laschever, and it completely changed how I operate.  I think many early career scientists could benefit from this book, which is about overcoming self-doubt to ask for what you really need. Although ostensibly written for women, in science I see so many men and women who could achieve something great with just a little confidence booster.

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Microparticles: Good things come in small packages

Microparticles were first described in 1967 by Peter Wolf, a physician, as ‘minute particulate materials’ when he investigated the platelet activity in human plasma. They were initially used as drug delivery agents because their size is as small as pollens, which can easily go into the human body. Not long after the great promise of microparticles has been realized, and today we use microparticles in numerous applications including pharmaceuticals, biomedicine, bioengineering, cosmetics, printing, and food science. The widespread use is not a coincidence, they can be synthesized from a multitude of materials, i.e. metal, polymer, gel etc. Especially, polymer microparticles, conferring a great versatility in size, shape, and chemistry, gained more attention in industry. Just like their usage areas, fabrication techniques of microparticles vary a lot. Polymer microparticle production is typically done in two ways, first microfluidics-assisted techniques including droplet-based fabrication, flow-lithography-based fabrication, and microjetting; second other techniques including centrifugation, electrohydrodynamics, and molding. With a focus on microfluidics-assisted techniques, we bring a few remarkable and commercialized studies on high throughput production of spherical-shaped and irregular-shaped microparticles to your attention.

Spherical microparticles

Particle monodispersity has to be compromised for high-througput production when using coaxial microfluidic devices, and both features are highly desired in medical applications and industry. Luckily, as a droplet-based fabrication technique, high-throughput step emulsification of microparticles addresses this fundamental problem. David Weitz’s research group at Harvard University has recently reported a droplet generator microchip with 135 step-emulsifier nozzles that produce monodisperse emulsions of polymers at an exceptional throughput of 10K mL/h (Figure 1a).1 This means, monodisperse microparticle production with this device is thousands times higher than a typical droplet generator microchip with one droplet maker and a throughput of 10 mL/h. The chip is made of PDMS, which is a flexible and inexpensive material. Monodispersity  at high flow rates is maintained using microchannels connected through an array of parallelized nozzles (Figure 1b). Microparticles are formed at the step between each nozzle and the continuous-phase channel. The formation can be explained by the Laplace pressure difference developing between the nozzle and the symmetric polymer bulb, resulting in suction of the dispersed phase into the bulb. The growing polymer bulb increases the pressure gradient and a neck forms between the nozzle and the bulb due to depletion of dispersed phase, resulting in release of a droplet. This geometry can produce spherical-shaped microparticles. The production efficiency scales linearly with droplet diameter (Figure 1c). Weitz demonstrated the production of oil microcapsules in water with the envision of standardizing the process by converting the emulsifier into a pipettor tip. Such a technology can replace the existing pipettor technology tools including multi-well and robots, and this replacement can serve for parallelizing and automation of the encapsulation chemi- and bio-assays. This technology has recently been introduced to the market by a Switzerland-based startup company called Microcaps.

As an alternative concept, in-air microfluidics is based on the idea of producing droplets at higher flow rates without using microfluidic channels. In the research groups of Detlef Lohse and Marcel Karperien at University of Twente, microparticles were generated using two nozzles, and one of the nozzles is mounted on a vibrating piezoelectric element (Figure 1d). The breakup of the liquid jet ejected from the first nozzle leads to formation of monodisperse droplets, which hit onto a continuous liquid jet ejected from the second nozzle. After passing ‘the meeting point’, both liquids react with each other to form physically-encapsulated microparticles. This technique provides with hundreds to thousands times faster microparticle production when compared to coaxial microchip setups. Such constructs can be especially beneficial in tissue engineering, where rapid fabrication of multi-scale materials with multiple cell types is an ongoing challenge. This technology has recently been introduced to the market by a Dutch startup company called IamFluidics.

Figure 1. Up-scaled step-emulsification device producing monodisperse droplets. (a) A schematic of the entire microfluidic chip actively producing oil-in-water droplets. (b) The emulsification process. (c) Maximum production rates per nozzle plotted against drop diameter, scale bars are 400 µm.The image is modified from Stolovicki et al. (see the references below). (d) Chip-based microfluidics comparison with in-air microfluidics.

Irregular-shaped microparticles

Another microfluidics-assisted fabrication concept is stop-flow lithography, introduced by Patrick Doyle’s research group at Massachusetts Institute of Technology.2 In this concept, while two (or more) streams of monomers flow side by side through a microchannel made of PFPE coated PDMS, the streams are exposed to intermittent illumination of ultraviolet light through a photomask, which blocks the light selectively. Due to the chemical reaction initiated by ultraviolet light, the liquid solidifies, and forms an individual microparticle (Figure 2a). Upon polymerization, gel particles do not stick to the PFPE microchannel walls, allowing for the production of free-floating particles by the virtue of oxygen lubrication layers. As the ultraviolet light is projected onto the stream through the photomask, each particle takes on the shape of the mask, making the microparticles customizable (Figure 2b). Microparticles composed of multiple monomers can be fabricated by combining multiple monomer streams. The single-step production is advantageous to reduce the production costs, however the particle shape is limited by the photomask and the microchannel geometry – not allowing for generation of spherical-shaped particles. For a proof-of-concept demonstration, upconverting nanocrystal laden-microparticles were synthesized and emitted homogenous visible spectrum of light. The technique allows for synthesis of striped microparticles without losing their homogeneous emission property. The microparticles were also encoded with multiple dot-patterns (Figure 2c), each specific to a target molecule (such as DNA) reacting with the other ingredients in the particle. Such a reaction leads to the formation of a fluorescent color in the microparticle, so the reaction can be traced by microscopy. This technology has been introduced to the market by Firefly Bioworks (acquired by Abcam in 2015), and Motif Micro (acquired by YPB Systems in 2018) startup companies.

microparticles

Figure 2. Stop Flow Lithography concept. (a) A schematic demonstration the coaxial microchip. (b) Bright-field and fluorescent images show triangle-shaped particles (c) A mask with an array of barcode particle shapes was aligned on three phase laminar flows in the microchip. Bright-field and fluorescent images show the barcoded particles with three distinct compartments with a region coding “2013”. The image is modified from Bong et al. (see the references below).

To download the full articles click the links below:

1Throughput enhancement of parallel step emulsifier devices by shear-free and efficient nozzle clearance
Elad Stolovicki, Roy Ziblat, and David A. Weitz
Lab Chip, 2018.
DOI: 10.1039/C7LC01037K

2Stop flow lithography in perfluoropolyether (PFPE) microfluidic channels
W. Bong, J. Lee, and P. S. Doyle
Lab Chip, 2014.
DOI: 10.1039/C4LC00877D

About the Webwriter

Burcu Gumuscu is a postdoctoral fellow in Herr Lab at UC Berkeley in the United States. Her research interests include development of microfluidic devices for single-cell analysis, next generation sequencing, compartmentalized organ-on-chip studies, and desalination of water on the microscale.

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Roll-to-roll PDMS-chips for the masses in molecular diagnostics

PDMS microfluidic devices for molecular diagnostics are now produced at scale using roll-to-roll manufacturing

If there is one material that has enabled microfluidic research in academia, poly(dimethylsiloxane) (PDMS) is surely it. PDMS is cheap and easy to prototype with, and its elastomeric properties have led to complicated structures (e.g. valving) in microfluidic channels. Although it is great for rapid prototyping, there is often a disconnect between the prototype and high throughput manufacturing due to a lack of scalable production methods. Researchers at VTT-Technical Research Centre of Finland and the University of California Berkeley have recently reported a roll-to-roll method for fabricating PDMS microfluidic chips.

In roll-to-roll (R2R) processing—common to the paper industry—long sheets of materials are continuously processed, feeding through rollers and modules with different functionalities. To form R2R microfluidic devices, PDMS was applied to an aluminized paper substrate and then embossed by a heated nickel imprinting cylinder which also cured the PDMS. The devices had good reproducibility and channel depths around 100 µm were achieved. Replication from the nickel master was automated and performed at high throughput of 1.5 m/min. Olli-Heikki Huttunen, one of the authors on the paper, said that “although the process required a lot of fine tuning, it was surprisingly simple.” Like other high-throughput manufacturing techniques (e.g. injection moulding), the nickel tool is quite expensive, but these costs can be overcome by the volume of production.

As a proof-of-principle application, the authors demonstrated nucleic acid detection by loop-mediated isothermal amplification (LAMP). Reagents were spotted and dried in the microchannels using a roll-to-roll compatible dispensing machine, and PDMS lids with vias for fluidic and vacuum connections were formed by a roll-to-roll process (though vias were manually punched) and then bonded manually. Huttunen said that the next steps are to figure out how to manufacture the entire device roll-to-roll, but that it should not be too challenging.

Using aluminized paper as the base substrate for the devices offered a couple advantages. One is that the aluminium dramatically reduced the paper’s autofluorescence. Another advantage was the aluminum reflected back both excitation and emission light, resulting in stronger signals. Results from the test could be read within 20 minutes, suggesting that these devices would be useful for low-cost point-of-care testing.

The challenge for the future, says corresponding author Luke Lee, will be “to learn what the new rules of thinking and design are for roll-to-roll microfluidics in order to solve the problem of mass production in integrated molecular diagnostics for all.” This is an exciting new prospect for both PDMS and the microfluidics community.

To read the full paper for free*, click the link below:

PDMS microfluidic devices for molecular diagnostics are now produced at scale using roll-to-roll manufacturing

*article free to read from 06/06/2018 – 06/07/2018

About the Webwriters

Darius Rackus (Right) is a postdoctoral researcher at the University of Toronto working in the Wheeler Lab. His research interests are in combining sensors with digital microfluidics for healthcare applications.

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