Cellular analysis array

Lab-on-a-Chip Screens Compounds to Accelerate Drug Development

Oct. 30, 2018
A simple, scalable CMOS device could save pharmaceutical companies time and money in their quest to discover new drugs.

Finding quicker, less-expensive ways to develop drugs—which is currently costly and time-consuming and has an astronomically high failure rate—could have far-reaching benefits both for healthcare and the economy. To speed the process and lower costs, researchers at the Georgia Institute of Technology designed a cellular interface out of low-cost electronics that measures several cellular properties and responses in real time. This could open the door to comprehensively testing many more potential drugs for efficacy and toxic effects much faster.

Pharmaceutical companies use cell-based assays, a combination of living cells and electronic sensors, to measure physiological changes in the cells. That data is used for high-throughput screening (HTS) during drug discovery. In this early phase of drug development, the goal is to identify target pathways and promising chemical compounds that could be developed further—as well as to eliminate compounds that are ineffective or toxic—by measuring the physiological responses of cells to each compound.

Testing the characteristics of thousands of candidate compounds, with the majority “failing early,” lets only the most promising ones be further developed into drugs and perhaps eventually to undergo clinical trials, where drug failure is much costlier. But most cell-based assays use electronic sensors that only measures one physiological property at a time and cannot obtain overall cellular responses. 

That’s where the new cellular sensing platform comes in. It lets researchers leverage the advances of nanoelectronics to create cellular interfaces with massively parallel pixels. Within each pixel, the device detects several physiological parameters from the same group of cells at the same time, including extracellular or intracellular potential recording, optical detection, cellular impedance measurement, and biphasic current stimulation. 

The new device has four advantages over existing platforms:

Multimodal sensing. The chip records several parameters on the same sample, letting researchers comprehensively monitor complex cellular responses, uncover the correlations among those parameters, and investigate how they may respond together when exposed to drugs. Taking a drug often causes several physiological changes, but this cannot be detected using conventional single-modal sensing.

Large field of view. The device lets researchers examine the behavior of cells in large groups to see how they respond collectively at the tissue level.

Small spatial resolution. Researchers aren’t just able to look at cells at the tissue level: They can also examine them at single-cell or even sub-cellular resolution.

Low-cost platform. The new device is built on standard complementary metal oxide semiconductor (CMOS) technologies, which is also used to build computer chips. It is process that can easily be scaled up for mass production.

Monitoring several cellular responses in several physical domains should also prove beneficial in screening out potentially harmful compounds. Many drugs have been withdrawn from the market after discoveries that they had toxic effects on the heart or liver, for example. This platform should let researchers comprehensively test for organ toxicity and other side effects in the initial phases of drug discovery.

The experimental chip may be useful for other applications, including personalized medicine. For example, it could check to see if drug worked specifically against cancer cells from a patient. Patient-to-patient variations in drug reactions can be huge, even with the same type of drug. The cellular interface could determine which combination of drugs would give the best response and to find the dose that is most effective with minimum toxicity to healthy cells.

In the future, cellular data from the chip could be uploaded and processed, and based on that, commands for new actuation or data acquisition could be sent to the chip automatically and wirelessly. So there could be warehouses containing culture chambers with millions of such chips in fully automated facilities, automatically conducting new drug selection for us.

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