Unlocking the future of next-generation cancer drugs

At Texas A&M University, one research lab is changing the game of droplet microfluidics, a technique that involves conducting experiments in nanoscale droplets of liquid in a controlled environment. The team developed a system that makes droplet microfluidics faster, lower cost, and more accurate. 

Dr. Arum Han, the Texas Instruments Professor in the Department of Electrical and Computer Engineering, and his lab, created a technology named NOVAsort (Next-generation Opto-Volume-based Accurate droplet sorter), a system that allows high throughput screening of molecules and cells at significantly reduced error rates. 

Whereas previous research has focused on increasing the speed of assays (a type of laboratory test), the team’s findings, which were published in Nature Communications, are among the first to significantly improve accuracy without compromising the speed of assays.

In the fields of biotechnology, healthcare and chemistry, there is a need to do a large number (millions and billions) of screening or testing of cells and molecules. However, one of droplet microfluidics’ biggest limitations, despite its major advantages in rapid testing, is a high degree of error in multi-step droplet operations, which is why this powerful technology has not been widely adopted and commercialized beyond a few very simple assays.

“Let's say you're a drug developer in the pharmaceutical industry or developing new high-value molecules in the biotechnology industry,” Han said. “You have to test millions of different drug compounds to see whether they are effective against a particular cancer cell, or test millions of different cells one cell at a time to find the most productive cells to develop a good cell strain. In another example, there are countless microorganisms out in the environment, and to find out which one might be most useful, or which one is doing what functions, you have to test millions and millions of individual cells one at a time.”

Conventionally, these experiments must be repeated via a time-consuming and costly process. With Han’s error-free NOVAsort technology, droplet microfluidics is poised to become a far more valuable technique in the pharmaceutical and biotechnology industry, in agricultural companies and in scientific research where conducting millions of experiments is crucial and often done manually.  

“If you test ten thousand or a million assays, then 5% error is a very large number. Our invention significantly reduces the error in this single cell or single molecule level screening in droplet microfluidics, so that, for example, from an error of 5% now you have an error of 0.01%,” Han said. “Using this method, you can run millions of assays, and still the false positive or false negative is very small. With this new technology, droplet microfluidics becomes an extremely powerful tool.”

The Impact

NOVAsort stems from a $15 million project funded by the Defense Advanced Research Projects Agency (DARPA) Han received in 2019. The goal was to go out into the field and isolate and retrieve soil and water samples to quickly identify potentially harmful microorganisms in those samples. To achieve this, Han and his team developed a technology to test millions of individual bacteria samples. 

“For that project, being fast and highly accurate was crucial because if you have a lot of error-prone results, you can incorrectly classify whether something is harmful or not,” Han said. “That was really driving our motivation to develop this technology: to reduce error so that when you go out and test millions and billions of microbes, the error rate is very, very low.”

Han’s multi-year DARPA project resulted in NOVAsort that can now be utilized broadly for civilian use. For example, this technology can be developed to help doctors make the best and most timely intervention strategy against diseases. 

“Let's say someone is infected by a pathogenic microorganism,” Han said. “Doctors try an antibiotic treatment, but the frontline of antibiotics don’t work. They have to quickly find which drug might be the best antibiotic at what dose to use against difficult-to-treat infectious diseases.”

Since Han’s new technology allows high throughput screening – testing millions of samples in a short time – this also means it can improve the speed and accuracy in the discovery of potential drug candidates with more precise results, including the next generation of cancer, anti-microbial and anti-fungal drugs.

In addition, this technology can find applications in biomanufacturing, which involves using biological systems to produce valuable products, chemicals and molecules. NOVAsort could accelerate the process of harnessing biological organisms that can produce highly useful molecules.

“We may be able to develop better drugs, better materials and better chemicals, potentially at a lower cost and that are more environmentally friendly and sustainable,” Han said.

With growing interest in computer-aided work such as artificial intelligence and machine learning, NOVAsort could also be used to generate a large number of high-quality, near-zero error data for researchers.

Collaboration and Future Efforts

NOVAsort is a collaboration between Han’s NanoBio Systems Lab and medical science expert Dr. Paul de Figueiredo, formerly of the Texas A&M Health Science Center and currently the NextGen Precision Health Endowed Professor at the University of Missouri. They have spent years working together on developing microfluidic technology and applying them to medical and biotechnology research, with further advancements to come. 

All of these microfluidic chips are being fabricated at the AggieFab Nanofabrication Facility, the state-of-the-art cleanroom facility of the Texas A&M University that is also being supported by the recent Texas Chips Act. 

“My lab has been working on the technological innovation, and the application of this technology is where we collaborate broadly with medical school and biotechnology professionals,” Han said. “As for the future of this technology, the goal is to achieve 0% error.”

“We are very proud of this work,” Han added. “We will continue to improve this technology by building microfluidic chips that can perform very complex experiments and apply this technology in broader ranges of applications to more rapidly conduct research and development, all while keeping the error as low as possible. Our focus is innovating the next generation microfluidic technology.”

 By Katie Satterlee, Texas A&M Engineering

###