Extreme High Throughput Screening Via Massively Parallel Droplet Dispenser Arrays

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PROJECT SUMMARY This project seeks to make drug discovery more effective by making the screening technology more accessible. Currently, new drug leads are discovered by testing a large number of unknown chemicals to see if any have the effect that you are looking for. Since this process is somewhat slow and expensive, such testing is not as thorough and widespread as it should be. We are trying to allow the chemical reactions to be run in microscopic droplets of liquid, which would greatly lower the cost of these reactions and make it possible to run many more together at once. To accomplish this, we are building a new device, a gigantic array of droplet dispensers. The array is envisioned to be large enough to hold the entire set of unknown chemicals that you are interested in testing. The array is very flexible. It can quickly dispense the entire set of chemicals, dispense many different concentrations of each chemical so that we can find the most effective dose, or dispense the chemicals in a variety of different combinations so that we can discover which drugs work well together. In order to make this array of dispensers work, we are using a new type of microchip technology where the circuits carry liquids instead of electrons. What is unique about our liquid circuits is that they can perform computations much like a computer can. This ends up being very useful for this project because we use this computational power to control the large array of dispensers. Once we build the droplet dispensers, we will test them out in various types of common screening experiments. We will try testing a library of chemicals against an enzyme that thought to be important in the spread of cancer. As part of this testing, we will try the variation where we try many different concentrations of each chemical, to find the dosage at which they start to become effective. Also, we will develop another system so that we can test our unknown chemicals directly on colon cancer cells, to see if any chemicals will kill the cells or slow down their growth. During these tests, we will take advantage of the device's ability to make different combinations of chemicals and drugs. Often, cancer cells need to be hit with multiple drugs in order to have a positive effect. Testing different drug combinations on these cancer cells will help us to discover new ways to combine drugs effectively. This work is less about the drug testing itself, but rather it's more about developing new ways to test possible drugs. Once we can show that our methods work, we can share our methods and hopefully help others discover new cures more quickly.