Honors & Awards
Fellow, National Defense Science and Engineering Graduate (NDSEG) Fellowship (2019-2021)
Education & Certifications
Master of Science, Stanford University, CS-MS (2018)
Bachelor of Science, Stanford University, BIOE-BS (2016)
Manu Prakash, Doctoral Dissertation Advisor (AC)
Current Research and Scholarly Interests
Medical devices are crucial for achievement of equitable access to health care, but the global medical device industry only minimally impacts rural and primary health care for poor people in low- and middle-income countries. Additional obstacles, including in the cost of medical device research & development and in last-mile implementation, make it hard for other entities to rectify the global market’s mismatch between the supply of medical devices and the health needs of poor people. To help challenge these contributing factors of global health inequity, we will synthesize a practical toolkit and intellectual framework for developing medical devices for low-resource settings in a distributed, cooperative, and open-source manner. The proposed framework aims to reduce the barriers for entities in low-resource settings to provide solutions which would be appropriate and affordable in their local contexts. We will use three ongoing Prakash Lab frugal technology projects, which I have been centrally involved in from early-stage development, as case studies of challenges and strategies to inform this framework. These case studies will specifically be used to answer the following questions:
1. How to achieve large-scale exploration & implementation of possible design variations and possible applications?
2. How to help clinicians achieve efficacy using new technologies in low-resource settings?
3. How to ensure medical device safety in globally distributed production of variations upon a reference design?
Each of the three projects (Handyfuge, Octopi, and Pufferfish) will implement and quantitatively assess the outcomes of strategies for distributed invention, development, and implementation of very distinct types of open-source medical devices, spanning in vitro diagnostics, digital pathology, and intensive care medicine, for low-resource settings. Through empirical investigation of the guiding questions as we develop and implement these technologies, we intend to lay the foundations of a new framework for large-scale development and implementation of appropriate open-source medical devices for global health equity.
Scale-free vertical tracking microscopy.
The behavior and microscale processes associated with freely suspended organisms, along with sinking particles underlie key ecological processes in the ocean. Mechanistically studying such multiscale processes in the laboratory presents a considerable challenge for microscopy: how to measure single cells at microscale resolution, while allowing them to freely move hundreds of meters in the vertical direction? Here we present a solution in the form of a scale-free, vertical tracking microscope, based on a 'hydrodynamic treadmill' with no bounds for motion along the axis of gravity. Using this method to bridge spatial scales, we assembled a multiscale behavioral dataset of nonadherent planktonic cells and organisms. Furthermore, we demonstrate a 'virtual-reality system for single cells', wherein cell behavior directly controls its ambient environmental parameters, enabling quantitative behavioral assays. Our method and results exemplify a new paradigm of multiscale measurement, wherein one can observe and probe macroscale and ecologically relevant phenomena at microscale resolution. Beyond the marine context, we foresee that our method will allow biological measurements of cells and organisms in a suspended state by freeing them from the confines of the coverslip.
View details for DOI 10.1038/s41592-020-0924-7
View details for PubMedID 32807956
Bacterial Evolution in High-Osmolarity Environments.
2020; 11 (4)
Bacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High-osmolarity environments therefore present formidable stress to bacteria. To explore the evolutionary mechanisms by which bacteria adapt to high-osmolarity environments, we selected Escherichia coli in media with a variety of osmolytes and concentrations for 250 generations. Adaptation was osmolyte dependent, with sorbitol stress generally resulting in increased fitness under conditions with higher osmolarity, while selection in high concentrations of proline resulted in increased fitness specifically on proline. Consistent with these phenotypes, sequencing of the evolved populations showed that passaging in proline resulted in specific mutations in an associated metabolic pathway that increased the ability to utilize proline for growth, while evolution in sorbitol resulted in mutations in many different genes that generally resulted in improved growth under high-osmolarity conditions at the expense of growth at low osmolarity. High osmolarity decreased the growth rate but increased the mean cell volume compared with growth on proline as the sole carbon source, demonstrating that osmolarity-induced changes in growth rate and cell size follow an orthogonal relationship from the classical Growth Law relating cell size and nutrient quality. Isolates from a sorbitol-evolved population that captured the likely temporal sequence of mutations revealed by metagenomic sequencing demonstrated a trade-off between growth at high osmolarity and growth at low osmolarity. Our report highlights the utility of experimental evolution for dissecting complex cellular networks and environmental interactions, particularly in the case of behaviors that can involve both specific and general metabolic stressors.IMPORTANCE For bacteria, maintaining higher internal solute concentrations than those present in the environment allows cells to take up water. As a result, survival is challenging in high-osmolarity environments. To investigate how bacteria adapt to high-osmolarity environments, we maintained Escherichia coli in a variety of high-osmolarity solutions for hundreds of generations. We found that the evolved populations adopted different strategies to improve their growth rates depending on the osmotic passaging condition, either generally adapting to high-osmolarity conditions or better metabolizing the osmolyte as a carbon source. Single-cell imaging demonstrated that enhanced fitness was coupled to faster growth, and metagenomic sequencing revealed mutations that reflected growth trade-offs across osmolarities. Our study demonstrated the utility of long-term evolution experiments for probing adaptation occurring during environmental stress.
View details for DOI 10.1128/mBio.01191-20
View details for PubMedID 32753494