Research Interests

Few topics of our current research interest are as follows:

High-precision flow control in complex microfluidic workflows for automated droplet packaging

Fluid flow control is the backbone of microfluidic systems, particularly when these systems incorporate multiple channels managing various phases. The control requirement escalates significantly when these systems are employed for encapsulating precise quantities of chemicals or materials within droplets. An interesting example of such operation is the screening of patient tumor samples against multiple drug combinations, enabling the rapid identification of the most effective drug pairings tailored to the unique genetic makeup of an individual's tumor, thereby circumventing the limitations of generalized cancer treatments1. Generating such combinatorial assays is challenging, primarily due to the complexity of controlling multiphase fluid flow to accurately produce droplets with the intended drug concentrations and combinations2. To address such problems, we aim to engineer instrumentation for multi-channel multiphase fluid-flow control for droplet packaging that is capable of generating high-precision biochemical assays in an automated manner3,4. We are also interested in utilizing this technology for controlled biochemical or biomaterial synthesis. The complete system development is aimed towards providing a translatable platform that is compatible with clinical requirements. Such a portable and cost-effect platform will aid applications like personalized therapy and disease monitoring, extending their benefits to a wider population.

Multiparametric high-throughput droplet screening platform for analysis of heterogeneous tumors

High-throughput droplet microfluidic platforms allow for the screening of millions of cells from both murine and human immune repertoires in a single experiment, facilitating the discovery of therapeutic antibodies5. Similarly, it also enables the screening of numerous droplets containing solid tumors or tumor cells alongside various drug combinations, aiding in the identification of the most effective personalized therapy1. For screening, droplets are analyzed in real-time through a combination of optics, electronics and high-speed computational modules following which, the droplets demonstrating the desired activity are physically sorted using dielectrophoretic forces3. While current screening platforms predominantly rely on fluorometric analysis to detect physiological changes within the droplet, morphological changes often remain unnoticed. We aim to develop instrumentation capable of deciphering the morphology of single cells by measuring their dielectric properties within the droplets6,7. These morphological readouts will not only offer a higher resolution for examining functional antibodies but will also be valuable in screening drug combinations for treating heterogeneous tumors, presenting a significant advancement in the precision and effectiveness of high-throughput screening platforms that are cost-effect and translatable to low-resource clinical setups. 

Single cell nucleic acid quantification to understand cellular heterogeneity

A major cause behind many diseases and syndromes is the change in copy number of certain specific chromosomal sequences and their heterogeneity in a supposedly isogenic cell population8 . Such changes include the presence of an extra copy of a complete chromosome, deletions of several base pairs or duplications of smaller chromosomal fragments. Copy number variation of specific chromosomal regions are also commonly found in tumors caused by uncontrolled gene expression. In addition, cell-to-cell heterogeneity for bacterial gene expression is also a commonly observed phenomenon that can attribute to pathogen survival. An example of bacterial heterogeneity as a threat for human healthcare is its association with the onset of persistence in Mycobacterium tuberculosis that infects one-third of the global population and claims two million lives every year9. Even though bacterial persistence is a phenotypic change, its roots have been found to lie with gene expression heterogeneities at the transcriptional level10.

We believe it is important to quantify the copy number variations at single cell level to develop insights over genesis and propagation of certain diseases. Therefore, we aim to develop technologies to quantify this heterogeneity by engineering new microfluidic workflows capable of counting number of RNA transcripts of known genes in every cell while also quantifying their physiological and morphological characteristics to establish a one-on-one correspondence between genotype and phenotype. 

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