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Microfluidics, meet superbugs

Microfluidics, meet superbugs

When my friends and family ask about my research, and I reply ‘microfluidics’, they always look confused and say, ‘Okay, what is that?’ This is not surprising since I didn’t know the word three years ago. The general public knows about scientific research in certain areas, like cancer, global warming, artificial intelligence and virtual reality. They either are problems we consider important or have applications we can relate to. But in the case of microfluidics, a distinct ‘feature’ is that its fame is mostly restricted to labs that deal with it. But if a technology were to be converted to productivity, people should know something about it, otherwise, they will not become users.

Commercialization of microfluidics has been a point of interest for a long time and has many researchers within the field frustrated. Back in 2006, George Whitesides raised this question in his inspiring paper1, yet more than a decade later we don’t seem to have any good answer.Some say we need a ‘killer app’2, while others point to the gap between academia and industry3. Whatever the reason may be, we can all agree that commercialization is an important step which microfluidics as a technology hasn’t been able to take. (more…)

Personalizing Medicine with the Organ-on-a-Chip Technology: Where Do We Stand?

Personalizing Medicine with the Organ-on-a-Chip Technology: Where Do We Stand?

Creating a miniaturized copy of yourself may sound crazy a decade ago, but not that much anymore – it is gradually realized by the organ-on-a-chip technology, little by little.

Imagine you get sick, you go to the doctor, who prescribes a medicine to you, most often empirically. You return to home, take the medicine, and heal. Or sometimes symptoms continue, or occasionally worsen. What do you do? You return to the doctor, complaining that the medicine does not work, and then receive another set of medicine, again very likely, by empiricism. The second medicine may heal you, or if unlucky, you may need to repeat this process for a few additional rounds prior to final recovery. Who knows. This scenario perhaps sounds familiar to most people, because it is how today’s medicine is practiced.A step forward, if the illness is much more serious than just a cold, modern technology may start to come into the play of its treatment. For example, patients with cancer typically receive molecular and genetic profiling to identify mutations, which are subsequently used to determine the class of drugs to prescribe. However, a biomarker often does not translate into a successful clinical response to the selected therapy. In a well-known case, cancer patients with wild-type KRAS protein are treated with Cetuximab, but only about 3 in 10 will ever respond to the drug, while the rest, unfortunately, instead of being cured, suffer side effects without noticeable benefits. (more…)

Organs-on-Chips and Animal Lovers: Dovetailing on the Medical Frontier

Organs-on-Chips and Animal Lovers: Dovetailing on the Medical Frontier

The impact of organoid research on popular culture is nowhere more evident than in the common ground between innovation and animal rights proponents. Organs-on-chips harbor the potential to reduce animal testing of new drugs and cosmetics. In 2017, the U.S. National Center for Advancing Translational Sciences funded 13 institutions with awards to develop tissue-on-chip models. Several of the awards mirror four-legged friends’ enduring goals.

Muscle disease is one example. One of the NCATS awards is for “Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease.” This Duke University project focuses on skeletal muscle and blood vessels. The models will replicate inflammation, in order to assess variation in responses to drugs. A similar award went to Cedars-Sinai Medical Center for “Development of a Microphysiological Organ-on-Chip System to Model Amyotrophic Lateral Sclerosis and Parkinson’s Disease,” to highlight novel biomarkers. There is no cure for ALS, a neurological condition that stops voluntary muscle movements including chewing, walking, talking and ultimately, breathing. Animal rights proponents welcome these endeavors because they have been vexed for years by the use of dogs for research that leaves them crippled with muscular dystrophy and unable to walk, swallow, or breathe. (more…)

Microfluidics Technologies for Circulating Tumor Cell Analysis: Opportunities and Challenges

Microfluidics Technologies for Circulating Tumor Cell Analysis: Opportunities and Challenges

Circulating tumor cells (CTCs) are tumor cells that are shed from cancerous tumors into the circulatory systems. CTCs are present in early-stage cancers and are reported to relate to disease prognosis. In recent years, CTCs have drawn increasing attention in both academic and industrial research, as they offer opportunities for the early detection, monitoring, treatment evaluation of cancer and its metastasis 1.

CTCs are challenging to capture, isolate and characterize in nature. First, CTCs are extremely rare in patients’ blood samples. One CTC usually exists among a background of millions of blood cells. Furthermore, CTCs are highly heterogeneous in physical characteristics and biological properties. No separation technology which is based on a single capture mechanism can produce pure and representative CTC subpopulations. In the traditional liquid biopsy, CTCs are isolated either by immunoaffinity strategies or by biophysical features differentiation. However, existing macro-scale isolation systems suffer important drawbacks, such as low capture efficiency, incomplete automation and low viability of captured CTCs 2. As a promising alternative, microfluidic technologies have gained tremendous interest in the field. Microfluidic technologies create devices that are at or smaller than the cellular length scale and enable accurate capturing and manipulation at single cell level. These technologies also offer precise control of fluid flow, which can greatly facilitate affinity reactions and physical separation. Moreover, on a microfluidic chip, CTC capturing and next-step analysis can be integrated to minimize intermediate sample handling and shorten the processing time. Above all, microfluidic approaches allow gentle isolation of live cells and thus enable many downstream analyses that rely on captured live CTCs 3. (more…)

Democratizing health care access in developing countries

Democratizing health care access in developing countries

In the past decade, technology advances have focused on generating comfort for a few. However, academics and entrepreneurs are shifting the luxury trend in order to serve society as a whole.

Scientific research was never meant to stay on papers. Just as Lab-on-a-Chip devices true destiny is in poor communities in developing countries. Academics all around the world have worked with a Lab-on-a-Chip concept, imagining that the power of a state-of-art laboratory could fit in their pocket. Contrary to popular belief, engineers and scientist are highly creative people, otherwise, they wouldn’t be able to imagine complex micro-manufacturing of chips to make health testing easier.

Jules Verne, a French author, image a vehicle that could go underwater in “Twenty Thousand Leagues Under the Sea.” Years later, visionary scientists were able to make a submarine made true. The military industry propelled this and others innovations, but after the war, they have been able to serve in deep oceans explorations. Today’s battles are not fought on fronts but with corruption and poverty.

Prof. Marc Madou from University of California, Irvine and Dario Mager from KIT university showing a lab-on-a-CD.

Prof. Marc Madou from University of California, Irvine and Dario Mager from KIT university showing a lab-on-a-CD. Credit: Monica Arreola

Lab-on-a-Chip is both a device and a sensor. By being a device the size of a human palm, the transportation is made easier. But in order to work as a laboratory, sensors need to be attached to the micro canals of the device. Inspiration à la Verne was what made Marc Madou build a Lab-on-a-Chip in the size of a CD-Rom. The professor of University of California, Irvine and of Tecnológico de Monterrey (Mexico) realized that while predecessors have managed to create the device and the sensors, there was still a need to analyze the results of the tests. (more…)

We Have Liftoff: Organs-on-Chips in Space

We Have Liftoff: Organs-on-Chips in Space

When British neuroscientists began developing brain organoids to study autism and schizophrenia some years ago, their colleague Dr. Martin Coath, of the University of Plymouth, publicly stated that they were fueling a crisis: “A human brain that was ‘fully working’ would be conscious, have hopes, dreams, feel pain, and would ask questions about what we were doing to it.”

Fears akin to Coath’s have trended ever since Mary Shelley wrote “Frankenstein” in 1818. While it is unlikely that organoids will be asking what we’re doing to them anytime soon, it is likely that they will be doing some space traveling.

The U.S. Center for the Advancement of Science in Space (CASIS), in collaboration with the U.S. National Center for Advancing Translational Sciences (NCATS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), plan to study organs-on-chips onboard the International Space Station-National Laboratory (ISS-NL). Data from this effort will contribute to research about microphysiological systems technologies. (more…)

Metastasis-on-chip and the future of medical microfluidics

Metastasis-on-chip and the future of medical microfluidics

Innovations in microfluidic modelling of the human body have enabled medical researchers to study pathology to a level of accuracy and efficiency that was previously unattainable.

These ‘disease-on-chip’ models build on previous advances in organ-on-chip technology, creating devices that can model disease processes specific to each modelled organ. Notable disease-on-chip innovations include Kambez Benam and colleagues’ model of human lung inflammation, and the device mimicking arterial thrombosis created by Pedro Costa and collaborators at the Universities of Twente and Utrecht. The key advantage of disease-on-chip technology over conventional disease models is that it facilitates assays that are both physiologically relevant and high-throughput.

One particular area in which such advantages promise to have enduring and significant impact is cancer biology, thanks to pioneering work done in modelling cancerous disease processes. Metastasis-on-chip is one such advance. (more…)

Two reasons to integrate simulations into your microfluidics workflow, now

Two reasons to integrate simulations into your microfluidics workflow, now

Over the last two years, I have seen an increased interest in using simulation software to better understand microfluidics processes. The two most common and important reasons for considering integration of simulation software into microfluidics processes have been to reduce device cost and improve quality control.

Microfluidics processes are truly multiphysics in nature, requiring a robust simulation tool to accurately capture all of the physics involved. Certain physics like surface tension become more prominent at the micro scales at which microfluidics processes work. Coupled to surface tension are other physics in play, such as electro-osmosis, electro-kinetics and visco-elasticity. In short, microfluidic simulations can be very complex. An accurate simulation tool can provide insights to the designer about the microfluidic device and help him develop a more efficient and better design. One such example is analyzing an acoustophoretic particle focusing device that removes a variety of objects from solutions in a microfluidic channel. The process is applicable to malignant cell removal, nanoparticle separation, and sequestration of suspended liquids. Another application is to understand the dynamics that govern the formation of lenses using fluids (optofluidics) in microfluidic channels. Optofluidics combines elements of optics and microfluidics and finds applications in biosensors, displays, lab-on-chip devices, molecular imaging and lenses.

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Organs-on-a-Chip revolution: Standing tall on the shoulder of giants

Organs-on-a-Chip revolution: Standing tall on the shoulder of giants

Drug discovery is a lengthy and costly endeavor. In fact, the cost of drug development has been rising year after year as result of a lack of physiological models that can accurately predict the effect of a drug in humans. Therefore, risky drugs may enter human clinical trials while promising drugs might be eliminated at early stages; both scenarios lead to a sizable financial loss. Organ-on-a-chip devices have emerged to combat this, and are poised to fill this gap where the conventional cell-based assays and animal testing    fail1,2. These technologies build on sophisticated microfluidic systems to culture human cells in a precisely controlled microenvironment to coordinate cells to work together and to recapitulate organ-level function that would otherwise be difficult to mimic in a traditional monolayer culture environment. The ultimate goal is to accurately model human physiology for precision drug testing.

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