Research

My research group focuses on the design and development of biochemical sensors for the understanding, prevention, diagnosis, and management of human diseases.  More specifically, we are working on the following three major research directions.

(1) Implantable neurochemical sensors. The human central nervous system contains billions of neurons that communicate through the propagation of action potentials along the cell membrane and the release, transport, and metabolism of neurochemicals at synapses. Technologies for in vivo electrophysiology have been intensively studied, with recent examples of Neuropixels 2.0 and Neural Matrix for recording over several thousand channels. Compared with these tools for electrophysiological recordings, the technologies for real-time neurochemical monitoring are very limited. My research group focused on developing next-generation implantable bioelectronics for probing chemical biomarkers in the brain. 

(2) CRISPR-based molecular diagnostics. Recently, the discovery of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated) systems has opened a new path for nucleic acid detection. Despite many advances, the current CRISPR-based biosensors in nucleic acid detection still require target preamplifications. The target amplification process often requires a set of proteins and primers (2-6) and additional sample preparation steps, which dramatically complicates and lengthens the detection process (20 min to 2 hours) as well as increases the contamination risk of patient samples. In addition, the target preamplification process is usually nonlinear and reaches saturation rapidly, limiting the ability to quantitatively measure viral copy numbers for predicting and/or monitoring disease progression. To solve these challenges in the field, my lab reported a biosensor, termed CRISPR Cas13a-gFET, for target amplification-free nucleic acid detection with an attomolar sensitivity via harnessing the trans-cleavage mechanism of CRISPR Cas13a and ultrasensitive graphene field-effect transistor (gFET) (Angew. Chem. Int. Ed. 2022, 61(32): e202203826).  This CRISPR Cas13a-gFET platform can be adapted to detect a variety of DNA targets for medical diagnostics, environmental monitoring, and food safety (ACS Sensors 2023, 8, 4, 1489–1499).  In a related line of research, my lab also co-invented an engineered LwaCas13a–electrochemical platform for ultrasensitive and target amplification-free nucleic acid detections (Nature Chemical Biology 2023, 19, 45–54). By including engineered LwaCas13a fusion proteins into a RNA redox-reporter-functionalized screen-printed electrochemical device, the platform detected the SARS-CoV-2 genome at attomolar concentrations from both inactive viral and unextracted clinical samples without target preamplifications.

(3) Wearable biochemical sensors. The ability for real-time monitoring of specific molecules in complex biological environments found in vivo has been reported to play an important role in the diagnosis and management of human diseases such as diabetes, cardiac diseases, acute kidney disease, and cancer. For example, the wearable continuous glucose meter (CGM), with the capability of real-time glucose monitoring for one to two weeks in the skin interstitial fluid, has revolutionized the effective management of diabetes. However, the CGM represents the only commercially available biosensor for real-time molecular monitoring in vivo. To that end, my lab has been working on wearable CGM-like platforms for monitoring biomarkers beyond glucose, including electrolytes, nutrients, and hormones. More specifically, my lab invented a wearable microneedle-based potentiometric sensing system for multiplexed and continuous monitoring of Na⁺ and K⁺ in the skin interstitial fluids (ACS Sensors 2021, 6 (6), 2181-2190). This study lays a foundation for developing wearable biochemical sensors for a wide range of biomedical applications, including real-time monitoring of nutrients, metabolites, and proteins.