Optimization and validation of a microfluidics- based static gradient generator for drug screening and drug discovery

8th Call
Developed by Abhijit Majumder, Prasanna Gandhi
Department: Chemical Engineering, Mechanical Engineering

Problem statement: Drug testing is an important step to decide on the type of drug and its concentration
that will be administered to a patient. This helps to select the most effective drug from a pool of potential ones. The conventional method involves testing drugs in multi-well plates. However, this process is error-
prone and time-consuming. The process gets more complex with the use of a combination of drugs. Flow-
based microfluidic gradient-generator address some of these issues. But they are still contamination-prone and not portable. The associated pumps and valves, high cost, etc. make it undesirable. A static microfluidic
gradient generator, which we propose can challenge these drawbacks of the conventional flow-based
microfluidic device. Our device will be inexpensive, portable, faster, and applicable to multiple drugs.

Project detail: The initial set of studies of the microfluidic device which is depicted in Fig. 1 is made by casting
PDMS on the template made by the Co-PI’s group. The device thus made has the stability to maintain a static
gradient for days. The stability of the static gradient maintained by this device was tested using a fluorescent
compound, FITC.

Using a numerical simulation (COMSOL) the concentration of the drug at different nodes was estimated. Cells were found to remain viable after 24hrs in the device. Another important test for cytotoxicity is to have equal
seeding i.e. equal cell density across the nodes. The cytotoxicity study of curcumin, which is an anticancer drug, was also tested on Glioblastoma cell line. The concentration of Curcumin at which cytotoxicity occurs was found to be the same as that reported in the literature.

The steps involved in the proposed project are:
i. Fabrication of microfluidic gradient generator which will be used for drug testing and cytotoxicity studies and establishing an operating regime for the device: This step involves testing the device using different drugs (different molecular weights). The design will be optimized to obtain a stable gradient for at least 24 hrs with the help of COMSOL simulations. These drugs will be tested on different cell lines (related to cervical cancer, breast cancer, and brain cancer).

ii. Develop device with different mesh layouts: This step will involve designing different mesh layouts (For eg. 5X5 mesh, 10X10 mesh, 15X15 mesh, and conventional 24-well and 96-well layouts), with their node layout similar to conventional multi-well plates. This will require additional modifications in the design.

iii. Fabricate the design using polystyrene (PS) instead of PDMS: While PDMS is easy to handle, it is not suitable for mass production. We will change the fabrication material to more durable polymers such as polystyrene. Initially, we need to check if the cells can survive in a polystyrene device. If the cells do not survive in a PS device, we will stick to PDMS as our fabrication material.

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