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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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A manufacturer’s 2 cents on developing microfluidic products

A manufacturer’s 2 cents on developing microfluidic products

Everyday clients share their microfluidic designs or products with contract manufacturing companies. Interestingly the designs can be classified to two types, let’s call them Type A or B, based on whether they exploit micron-size specific behavior of fluids or not. These small scale phenomena include surface tension, electrical, magnetic or shear force, etc… which may behave differently in a 30 micron dia. channel compared to a 1mm dia. channel for similar designs.

Type A devices exploit the micron scale behavior to achieve a novel function. A Type A product offers something new that probably is not feasible if the design is scaled 10 times larger. Type A designs are therefore innovative or perhaps disruptive. On the other hand, Type B devices offer to miniaturize, integrate or automate existing fluidic products or processes. The value proposition for type B products may include “cheaper”, “faster” or “more accurate” words.

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