Research Spotlight: Creating microfluidic transistors that control the movement of fluids to autonomously execute miniature lab operations

Kaustav Gopinathan, an MD-PhD student in the Center for Engineering in Medicine and Surgery at Mass General, is the first author of a new study in Nature, Creating a microfluidic transistor that mimics the function of the electronic transistor, but controls fluids and reagents instead of electricity.

Mehmet Toner, PhD, an investigator in the Center for Engineering in Medicine and Surgery and a professor of Surgery and Health Sciences and Technology at Harvard Medical School, is senior author of the paper.

What was the question you set out to answer with this study?

Can we control reagents, cells, and droplets in microfluidic devices with a similar level of precision and complexity with which electronic transistors can control the movement of electricity?

Microfluidics—the science of creating miniature devices containing chambers and channels that liquids flow through—has enabled innovative advances in molecular biology, synthetic chemistry, diagnostics and tissue engineering.

However, there has long been a critical need in the field to manipulate fluids and suspended matter with the precision, modularity and scalability of electronic circuits.

Just as the electronic transistor enabled unprecedented advances in the automatic control of electricity on an electronic chip, our goal was to create a microfluidic analogue to the transistor which could enable improvements in the automatic control of reagents, droplets and single cells on a microfluidic chip.

What Methods or Approach Did You Use?

In this paper, we exploited a special fluidic phenomenon originally studied in the medical physiology literature, called flow limitation, to develop a microfluidic element that replicates the behavior of the electronic transistor but operates on pressures and flows instead of voltages and currents.

Since this microfluidic transistor had behavior that was closely analogous to that of the electronic transistor, we were able to draw upon the extensive analysis, tools, and fabrication techniques from the electronics industry to study and develop our microfluidic analogue to the transistor in microfluidic circuits.

What Did You Find?

Our primary result was that we could exploit the phenomenon of flow limitation to create a microfluidic analogue to the electronic transistor which could also be fabricated at scale. We also showed that with this analogous element we could translate a wide range of both fundamental and complex electronic circuit designs directly into the microfluidic domain. In doing so, we could leverage the highly developed electronic circuit design repertoire to create analogous microfluidic circuits that could perform a variety of operations on chemical reagents.

Finally, while electronics is limited to manipulating electricity, we found that we could use our microfluidic transistor circuits to manipulate the movement of matter suspended in fluid for single-particle operations. We were able to build a self-contained microfluidic circuit block that could sense, process, and controllably dispense individual particles in an automated fashion, without the use of electronic computers.

What are the Implications?

Biological and chemical labs often perform operations where cell solutions, reagents, or drugs are manipulated and mixed in complex ways to perform experiments. Conventional labs are often limited by the speed and scale at which they can perform these fluid operations.

In electronics, having a transistor meant that we could build electrical circuits that could execute highly complex operations on electrical signals for us at scale. While there is still much more to optimize and explore with our microfluidic technology, we hope to perform similarly complex operations on cells, chemical reagents, and droplets at scale to automate aspects of drug development, biological sample processing, and multiplexed molecular biology assays.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.