Emerging Investigators series – Steve Shih

We are delighted to introduce our latest Lab on a Chip Emerging Investigator – Steve Shih!

Steve Shih completed his BASc in Electrical Engineering from Toronto and then went to University of Ottawa to complete his Master’s degree in Chemistry. He then returned to Toronto to complete his Ph.D in Biomedical Engineering in Aaron Wheeler’s laboratory.  He then spent two years at UC Berkeley and at the Joint BioEnergy Institute (JBEI) as a postdoctoral researcher and worked closely with collaborators Jay Keasling and Nathan Hillson.  He learned pathway engineering of microbes for biofuel production using synthetic biology tools and published four papers related to this research.  As of January 2016, he became an Assistant Professor at Concordia University in the Department of Electrical and Computer Engineering with appointments in the Department of Biology and the Center for Applied Synthetic Biology.  His current research entails combining new microfluidic platforms with synthetic biological tools to solve challenges in the health, energy, and medical fields.

Read his Emerging Investigators paper “Image-based Feedback and Analysis System for Digital Microfluidics” and find out more about his research in the interview below:

Your recent Emerging Investigator Series paper focuses on an image-based feedback system for digital microfluidics How has your research evolved from your first article to this most recent article?

Wow it has evolved immensely! I started off as a naïve graduate student dabbling in the field of NMR and using that technique to determine structures of membrane proteins. My first paper described how we used computational and experimental techniques to optimize the determination of membrane protein structures. I learned so much in the field of chemistry and molecular biology, especially coming from an engineering background.

Now my research is in microfluidics and I am using this technique to solve some challenging biological problems.  Although the topics are completely different – the techniques that I learned previously has helped to find interesting solutions to engineering problems.  I am always excited to dabble in new and exciting fields and integrating traditional fields with the new.

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

I just recently started my lab and there are so many exciting new projects. My lab is currently working on integrating microfluidics and automating processes related to synthetic biology. Synthetic biology has evolved towards engineering new organisms to produce vast quantities of valuable products, such as biorenewable fuels. This promise (and among many others) has been inspired by biologists that believe genetic engineering of biological cells can be more like the engineering of any hardware. However, challenges loom at multiple steps in the process and our lab is using microfluidics that will overcome these (or least some) challenges.

In your opinion, what is the biggest advantage of this technology and how will this impact digital microfluidics?

I am very excited about this paper because it is the first time that imaging techniques for feedback has been applied to digital microfluidics. One of the biggest challenges with digital microfluidics is the reliability of droplet movement – i.e. an application of a potential does not always equate to a droplet movement. This problem is exacerbated when we are multiplexing droplet movement – more droplets will fail during operation. We have developed a method in which we can individually detect all the droplets on the device using image-based techniques. This is a huge advantage since we only require applying a feedback mechanism to only those droplets that failed in movement while it does not delay the movement of other droplets that translated successfully on the device. This optimizes the time a droplet rests on an electrode and can minimize other effects that prevent droplet movement (e.g., biofouling).

What do you find most challenging about your research?

Everything, but this is why I love my inter-disciplinary research field since it involves so many different aspects. Some examples are trying to understand the underlying mechanisms of breast cancer to resolving issues of integrating synthetic biology techniques at the microscale.

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

I will be attending MicroTAS this year in Savannah and two of my students will be presenting posters. I will also be attending the 4BIO gene editing and synthetic biology conference at London, UK in December, where I will be giving a talk to describe some our microfluidic work with synthetic biology.

How do you spend your spare time?

Spare time is so rare among new professors. But I spend most of my time chasing my kids and trying to excite them for what is to come…

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

This is a tough question. I really love my job as an educator and everything else that comes with it. But if I had to choose something else, I think I would be a sports broadcaster on ESPN. I love sports and I am an avid fan of tennis and basketball. It would be my dream to commentate a Roger Federer game or to call a Toronto Raptors game.

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

Failure is inevitable. I failed so many times during my career and it is all part of the learning process. Young scientists should embrace failure and learn as much as they can from it – don’t be afraid of it! They do not realize that failure is where new innovation and ideas come from. I definitely would not be where I am today if it was not for failure.

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Personalised Medicine: Liquid Biopsy

We are delighted to announce our latest Thematic Collection in Lab on a Chip – Personalised Medicine: Liquid Biopsy!

This collection is being lead by Thought Leaders Stefanie Jeffrey and Mehmet Toner.

Stefanie Jeffrey, MD, is the John and Marva Warnock Professor and Chief of Surgical Oncology Research in the Department of Surgery at Stanford University School of Medicine. Her lab focuses on technology development and applications related to liquid biopsy (CTCs, ctDNA, extracellular vesicles), droplet-based microfluidic platforms, and preclinical models for testing new cancer therapies.

Mehmet Toner, PhD, is a member of the faculty at the Center for Engineering in Medicine at Massachusetts General Hospital. Dr. Toner is motivated by multi-disciplinary problems at the interface of engineering and life sciences. In the fields of microfluidics/micro-engineering/cancer he is working on microfluidics in biology and medicine including microfluidic blood processing, developing a microchip to help sort rare cells and integration of living cells and micro-engineered tissue units into micro-devices.

Liquid Biopsy, coined by Pantel and Alix-Panabières in 2010, originally referred to real-time analyses of CTCs in cancer. However, that term has since expanded to encompass the analyses of many other disease-related substances found in blood and other body fluids. Our goal is to highlight the new advances in this growing field with an emphasis on the interface between the technological advancements and high impact applications of liquid biopsy technologies. These would include manuscripts related to components that can be captured or characterized from blood such as circulating tumour cells, circulating nucleic acids and circulating extracellular vesicles.

Interested in submitting to the collection?

If you are interested in submitting to the personalised medicine: liquid biopsy collection, please contact the Lab on a Chip Editorial Office at loc-rsc@rsc.org  and provide a title and abstract of your proposed submission.

Articles will be published as they are accepted and collated into an online Thematic Collection, which will receive extensive promotion. Read the collection so far – http://rsc.li/liquid-biopsy 

Submissions for this collection are open from 1st September 2017 to 30th June 2018

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Droplets droplets everywhere: optimising genetic circuits using cell-free extracts and droplet microfluidics

Written by Yuval Elani, EPSRC Research Fellow at Imperial College London

The design and engineering of biological systems — a field known as Synthetic Biology —has been heralded by many to be the defining technology of the 21st century. Just as electronics and computers have changed almost every facet of our day-to-day lives, the consequences of engineering microbes might also be as far reaching. Engineered bugs are already being developed to produce pharmaceuticals and fuels, monitor their environment, detect trace chemicals, degrade plastic waste, and perform computing operations.

Microbes, however, are considerably more complex — and hence less predictable — than electronic components. For this reason, one of the best strategies scientists have for engineering them is to use a brute force approach: try out as many different biodesigns as possible and see what works best.

Doing this with microbes is tricky. Designing and constructing a single engineered bacteria is labour intensive and can take weeks. To circumvent this, researchers have turned to cell-free systems: a collection of biomolecules that can reproduce biochemical features of interest, for example the synthesis of proteins from a genetic circuit. This greatly simplifies things as after all you are now merely handling what is essentially a sack of chemicals.

This is where it really gets interesting. As opposed to testing out different genetic circuits one-by-one in a test tube, Hori et al developed a microfluidic device which forms millions of droplets an hour – each droplet acts as a mini test tube, each containing a slightly different version of the circuit. The circuit was made up of three strands of DNA which interact with one another in a non-linear way to produce a Green Fluorescent Protein. The fact that it is non-linear means predicting how they interact is difficult and makes the tactic of trying out different combinations more appealing. Using microfluidics, the authors created a generic library by combining different ratios of these three components. By incubating the droplets and monitoring protein production levels, they were able to map out the parameter space to see which genetic circuit from their library worked best.

Although simply a proof-of-concept, this droplet microfluidic approach has shown to be incredibly powerful, and in addition to being used in genetic circuit design has the potential to rapidly explore large parameter spaces in other areas of chemistry and biology.

 

 

 

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

Cell-free extract based optimization of biomolecular circuits with droplet microfluidics
Yutaka Hori, Chaitanya Kantak, Richard M. Murray and Adam R. Abate
Lab Chip, 2017
DOI: 10.1039/C7LC00552K

*Free to access until 8th September 2017.

 


About the Webwriter

Yuval Elani is an EPSRC Research Fellow in the Department of Chemistry at Imperial College London. His research involves using microfluidics in bottom-up synthetic biology for biomembrane construction, artificial cell assembly, and for exploring bionterfaces between living and synthetic microsystems.

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New YouTube Videos

Holographic microscope slide in a spatio-temporal imaging modality for reliable 3D cell counting

 
Droplet Trapping and Fast Acoustic Release in a Multi-height Device at Steady-state flow

 

Microfluidic Co-flow of Newtonian and Viscoelastic Fluids for High-resolution Separation of Microparticles

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Euroanalysis 2017

Euroanalysis 2017, will be held from 28th August – 1st September 2017, in StockholmSweden.

Along the lines of the long traditions of Euroanalysis, the meeting will cover all aspects where analytical chemistry plays a role including fundamental and applied sciences. It will offer plenary and keynote presentations on cutting-edge topics by internationally renowned leaders of the field, followed by contributed talks and poster presentations to stimulate interdisciplinary discussions. In addition, a young researchers’ session will be organized to provide opportunities for and encourage Ph.D. students and postdocs to share their findings.

The conference has attracted about 500 participants from more than 30 countries, covering academia, governance and industry. The organisers hope that this will help to strengthen the networks between chemical societies and their members, working in diverse fields.

In addition to the lectures offered in the program, there are also opportunities to visit the exhibition, attend short courses and vendor’s seminars. A number of prominent analytical chemists will also be awarded.

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Emerging Investigator Series – Leidong Mao

We are delighted to bring you the first interview for our Emerging Investigators Series in Lab on a Chip!

Leidong Mao is currently an Associate Professor and a distinguished faculty fellow in the School of Electrical and Computer Engineering of College of Engineering at the University of Georgia, USA. He received his B.S. degree in Materials Science from Fudan University, China in 2001 and his Ph.D. degree in Electrical Engineering from Yale University, USA in 2008. He was a recipient of the Faculty Early Career Development (CAREER) award from the US National Science Foundation in 2012, and the Young Scientist Award at the international conference on magnetic fluids in 2013. His current research interests include developing novel microfluidic technologies for biology and biomedical sciences. Examples of the projects in his lab include label-free cell separation technology that can isolate extremely rare circulating tumor cells from patient blood for cancer research and clinical applications, studies of circadian rhythm of single cells and their mechanism of synchronization, and diseases-on-chip models such as stroke-on-a-chip and glioma-on-a-chip. In addition to the research activities, he developed an interdisciplinary research and education program since 2014 for undergraduate students in nanotechnology and biomedicine, through a Research Experiences for Undergraduate (REU) grant from the US National Science Foundation.

Read his Emerging Investigators paper Label-free ferrohydrodynamic cell separation of circulating tumor cells and find out more about his research below:

Your recent Emerging Investigator Series paper focuses on the separation of circulating tumour cells. How has your research evolved from your first article to this most recent article?

My first paper as a graduate student studied the mechanism of ferrofluid actuation under a traveling magnetic field through modeling and simulation. On the surface, there seems to be a drastic change between the first paper and this recent paper. However, there was similar thinking behind these two projects – building models and systematic optimization were valued in both cases. Nonetheless, this recent paper involved a lot of cancer research, thanks to my fantastic collaborators.

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

Circulating tumor cells (CTCs) are very interesting to study but difficult to isolate. I am excited about the high recovery rate and biocompatibility of our technology, and the prospect that it may be integrated with other technologies for a more efficient way to separate intact CTCs from patient blood.

In your opinion, what is the biggest challenge for the separation of CTCs from blood?

This is a complex problem. High throughput, high recovery rate, high purity and excellent biocompatibility are four important criteria in CTC separation. Being able to meet all four criteria is challenging for a single technology, whether it is label-based or label-free.

What do you find most challenging about your research?

Learning biology as an engineer. For me, it is challenging but fun.

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

Microtas 2017 in Savannah Georgia, USA

How do you spend your spare time?

Spending time with my family.

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

Never a question to me, this is what I wanted to do.

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

It helped me a lot when I started as an Assistant Professor to have a few highly motivated graduate students.

 

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New YouTube Videos

Multifunctional optofluidic lab-on-chip platform for Raman and fluorescence spectroscopic microfluidic analysis

 
An automated optofluidic biosensor platform combining interferometric sensors and injection moulded microfluidics

 

Characterisation of anticancer peptides at the single-cell level

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3D Printing Truly Micro Microchannels

Written by Darius Rackus, postdoctoral researcher at University of Toronto

A new 3D printer and resin formula enable 3D printing of channels on the microscale

 

There is no doubt that 3D printing is a hot technology with applications across all sectors of industry and life. The technology is attractive not only for its use in rapid prototyping, but also for its ability to form complex structures that could not easily be formed by other manufacturing techniques. There is also the added benefit of digital design—it is very easy to go from a CAD model to physical production without the need of additional tooling or equipment. For these reasons and others, 3D printing is an attractive manufacturing process for microfluidics.

Albert Folch has argued that 3D printing is the solution to the barriers preventing the translation of PDMS microfluidics to commercial applications. (Angew. Chem. Int. Ed. 2016, 55, 3862–3881.) However, printing resolution has limited the size of channels to the milli- and sub-millifluidic regimes. The challenge when it comes to microchannels is that commercial 3D printers are designed to form polymer features but microchannels, by their nature, are voids within bulk material. While many 3D printer manufacturers tout resolutions in the tens of micrometers, the reality is that the resolution of the void spaces can be several-fold larger. In their recent report, researchers at Brigham Young University have advanced 3D printing technology to print channels truly in the micro- regime.

 

Left: Schematic illustration of 3D stacked serpentine channel design. Right: SEM image of 3D serpentine channel cross section.

Achieving true micro-scale printing resolution required innovation in both the 3D printer and the resin material. Gong et al. modified a digital light processing (DLP)-type 3D printer to include a high resolution light engine and a 385 nm UV LED light source. DLP printers project a pattern of light over the entire plane, crosslinking an entire layer in a single step. The light engine enables resolutions in the x-y plane of 7.6 µm and their choice of a 385 nm light source opened a wide range of possible UV-absorbers to them. Twenty different UV-absorbers were evaluated and 2-nitrophenyl phenyl sulfide (NPS) was chosen as having all the desired properties, with the main criterion of enabling smaller void sizes in the z-dimension. The final composition of the resin was a mixture of poly(ethylene glycol) diacrylate (PEGDA), NPS, and Irgacure 819. This mixture created structures that have low non-specific adsorption and had good resolution in the z-axis. Additionally, the structures could be photocured with a broad-spectrum UV lamp after printing.

Despite high-resolution printers and materials, a new printing regime also had to be developed to achieve the desired channel width. Because of scattering, the area of crosslinked resin tended to be smaller than the actual pixel size. This meant that channels, which are essentially voids of non-exposed space, came out wider than designed. The solution that Gong et al. devised was to perform two print patterns for each exposed layer. The first print pattern exposes the entire area, save for the channel void and the second exposure only projects a pattern along the channel walls. This method enabled reproducible printing of channels with a ~20 µm width.

3D CAD model of the custom 3D printer by Gong et al.

 

So how soon can you expect to get your hands on a 3D printer capable of printing true microchannels? While this report has been very promising, it is currently the only printer and only resin formulation with these capabilities. According to Greg Nordin, the corresponding author, the main challenge is to figure out “how to get this into people’s hands in a convenient way so they don’t have to mess around much to get it to work.” Like any new technology, for it to be truly useful, users want to spend more time making and less time fiddling. Fortunately, there already are markets for printing small, intricate parts, such as jewelry and dentistry, so it’s only a matter of time before manufacturers catch on to the market for 3D printed microfluidics.

 

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

Custom 3D printer and resin for 18 μm × 20 μm microfluidic flow channels
Hua Gong, Bryce P. Bickham, Adam T. Woolley and Gregory P. Nordin
Lab Chip, 2017
DOI: 10.1039/C7LC00644F

*Free to access until 29th August 2017.


About the Webwriter

Darius Rackus 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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TISuMR 1: Symposium On Tissue Culture and Magnetic Resonance

The first TISuMR Symposium on Tissue Culture and Magnetic Resonance will take place from 24th – 27th September2017, in WinchesterUK.

The culture of tissue under controlled conditions holds great promise for the future of medicine and the life sciences in general. While the study of cells provides detailed insight into biological processes at the molecular and supra-molecular scale, understanding many disease processes requires a more systemic approach.

Culture of  tissues, either from organ samples or grown entirely in vitro, can provide insight at the organ system level, revealing not only the function of individual cell types, but also their interaction with each other as well as with the extracellular matrix.

Combining advanced microfluidic lab-on-a-chip approaches to tissue culture with non-invasive, in-situ NMR investigation of life processes is the central theme of the TISuMR project. This symposium will bring together clinical experts on liver pathology,  researchers working on microfluidic tissue culture,  and scientists developing novel magnetic resonance techniques, with the following aims:

  • Exchange ideas across discipline boundaries.
  • Discuss opportunities and challenges in the field.
  • Establish the potential of the TISuMR approach for developing liver disease models.
  • Foster mutual understanding between the biomedical and technical aspects of the project.

The technical program will feature a number of leading scientists in the fields of hepatology, microfluidic technology, and magnetic resonance as keynote speakers. In addition, members of the TISuMR team will present their projects and early results.

Register here for the conference

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How can biosensors provide real-time health monitoring?

Like a ripple spreading outwards on a pond’s surface, a plasmon is a collective oscillation of free electrons in a piece of metal. When the metal interacts with light (in this case k vector of light satisfies the momentum condition), the collective movement of oscillating electrons at the metal’s surface leads to the propagation of the light along the surface, also known as a surface plasmon. This simple physics rule is very helpful for sensor nanotechnology and optical signal processing applications since the offered advantages are significant, providing a smaller foot-print, lower limits of detection, and multiplexing opportunities. However, using sensors for biomolecule detection requires clever use of light. For example, surface plasmon resonance can be observed in nanohole arrays patterned on very thin gold films. Nanohole arrays can transmit light much more strongly than expected for the nanohole apertures at certain wavelengths. This phenomenon is called extraordinary optical transmission (EOT) and opens a new avenue for detection of minute amounts of biomolecules.

A nanoplasmonic biosensor was recently developed for real-time monitoring of proteins from live cells in a label-free configuration, thanks to extraordinary optical transmission. The biosensor is structured in a microfluidic device consisting of a cell module and the biosensor module. Microfluidic cell module design is based on a single zigzag channel for directly delivering the secreted proteins to the adjacent biosensor module via a tubing connection. The biosensor module consists of nanoholes fabricated on freestanding SiNx membranes. Antibodies specific to vascular endothelial growth factor (VEGF) are selectively immobilized on the gold nanohole arrays as biorecognition molecules. When the VEGF are captured on the sensor, a change of refractive index proximate to the surface is induced. This change results in a peak shift of the EOT spectrum (Figure 1). By tracing the spectral shifts continuously, the dynamics of cell secretion can be monitored. In this way, the secretion dynamics from live cancer cells are monitored and quantified for 10 hours. The proposed microfluidic device has unique capabilities for multiplexed and label-free detection in a compact footprint, which are promising for miniaturization and integration into lab-on-a-chip devices.

biosensor, microfluidics, extraordinary transmission phenomena, nanohole arrays

Design and working principle of microfluidic-integrated biosensor. Cancer cells grow in a zigzag channel, and secreted vascular endothelial growth factor are directly delivered to the adjacent detection module. Nanohole structures fabricated in the detection (biosensor) module are shown in SEM image with a scale bar of 1 μm (bottom left). The images on the right show the characteristic resonance peak (solid line) and EOT spectral shift of the peak upon binding (dashed line). Spectral displacements of the resonance peak based on molecular binding accumulation is shown in the sensorgram to reveal the real-time binding dynamics. Adapted from Li et al. (Lab Chip, 2017).

This technology will have a potentially significant impact on medicine. Most of the patients agree that preventive medicine is preferable to reactive medicine. However, preventive medicine requires frequent physical exams, which can only be maintained by spending substantial time and money at physicians’ offices. The need for frequent check-up exams could be reduced or eliminated by real-time monitoring of the health status by portable biosensors in the future. Developing biosensors that allow real-time monitoring of target biomolecules is a big step towards the addressing this future goal.

 

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

Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion

Xiaokang Li, Maria Soler, Cenk I. Özdemir, Alexander Belushkin, Filiz Yesilköy and Hatice Altug

Lab Chip, 2017

DOI: 10.1039/C7LC00277G

 

*Free to access until 7th August 2017.


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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