The Zhang lab develops next-generation bioelectronics and biosensors to understand, diagnose, and treat human diseases. More specifically, we are working on the following major research directions.
(1) Implantable neurotechnology. 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. Beyond the brain, with the support from the NSF CAREER award, my lab is working on the fundamental understanding of materials, biosensor design, and system integration of multimodal biosensors in the GI tract , and will develop implantable bioelectronics for simultaneously interfacing with both the brain and gut (to study the gut-brain axis) in the next 5-10 years.
Funding sources: NIH Brain Initiative RF1NS118287, NIH NIMH R01MH128721, and NSF CAREER award (ECCS-2238273).
Representative publications:
1. H. Sun, X. Xue, G. L. Robilotto, X. Zhang, C. Son, X. Chen, Y. Cao, K. Nan, Y. Yang, G. Fennell, J. Jung, Y. Song, H. Li, S. Lu, Y. Liu, Y. Li, W. Zhang, J. He, X. Wang, Y. Li, A. D. Mickle*, Y. Zhang*, “Liquid-based encapsulation for implantable bioelectronics across broad pH environments”, Nature Communications 2025, 16, 1019.LINK
2. Y. Qiang, X. Zhang, X. Xue, L. Homer, G. Jos, Z. Weng, H. Li, I. Kim, Y. Zhang*, “An implantable, ultralow distortion bioelectronic interface integrating light-emitting diodes and graphene field-effect transistors”, ACS Nano, 2025, 19, 32, 29228–29241.LINK
3. G. Wu, I. Heck, N. Zhang, G. Phaup, X. Zhang, Y. Wu, D. E. Stalla, Z. Weng, H. Sun, H. Li, Z. Zhang, S. Ding, D. P. Li, Y. Zhang*, “Wireless, battery-free push-pull microsystem for membrane-free neurochemical sampling in freely moving animals”, Science Advances 2022, 8, eabn2277. LINK
4. G. Wu, N. Zhang, A. Matarasso, I. Heck, H. Li, W. Lu, G. Phaup, M. J. Schneider, Y. Wu, Z. Weng, H. Sun, Z. Gao, X. Zhang, S. G. Sandberg, D. Parvin, E. Seaholm, S. K. Islam, X. Wang, P. E. M. Phillips, D. C. Castro, S. Ding, D. P. Li, M. R. Bruchas, Y. Zhang*, “Implantable aptamer-graphene microtransistors for real-time monitoring of neurochemical release in vivo”, Nano Letters 2022, 22, 9, 3668–3677. LINK
5. Z. Gao, G. Wu, Y. Song, H. Li, Y. Zhang, M. J. Schneider, Y. Qiang, J. Kaszas, Z. Weng, H. Sun, B. D. Huey, R. Y. Lai, Y. Zhang*, “Multiplexed monitoring of neurochemicals via electrografting-enabled site-selective functionalization of aptamers on graphene field-effect transistors”, Analytical Chemistry 2022, 94, 24, 8605–861
(2) Instrumented brain organoid systems. Human brain organoids are miniaturized, self-organizing neural tissues derived from three-dimensional (3D) cultures of pluripotent or tissue-resident stem cells. They have rapidly become a transformative platform for modeling human brain development and neurological disorders, personalized medicine, drug screening, neurotoxicity assessment, and many others. The brain organoids hold great promise for improving human pharmacological efficacy with reduced reliance on small animal models. This potential has been further amplified by the United States Federal Drug Administration (FDA) Modernization Act 2.0, which allows drugs thoroughly tested in non-animal models, including organ-on-a-chip and organoids, to proceed to clinical trials, upon FDA approval. Despite this potential, comprehensive functional evaluation of brain organoids remains a major bottleneck. In particular, high-resolution mapping of neural activity in 3D tissues, essential for understanding network maturation, pathological circuit remodeling, and drug responses, is still constrained by conventional two-dimensional (2D) multi-electrode arrays (MEAs). These planar, rigid devices restrict electrophysiological interfaces to the basal surface of organoids, preventing access to the complex 3D architecture. To tackle these issues, my lab is working on integrating bioelectronics and biosensors with organoids to develop instrumented organoid systems for studying human neural development, disease modeling, and drug response.
Funding sources: NIH R21EB033495.
(3) CRISPR-based molecular diagnostics. Molecular diagnostics, in particular, nucleic acid testing, is critical in a wide range of fields relevant to the quality of human life. Over the past few decades, quantitative polymerase chain reaction (qPCR) has remained the gold-standard technique for nucleic acid testing. However, qPCR is limited by expensive instruments, the need for operation by well-trained personnel, and long sample-to-results time. 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 tackle these challenges in the field, my lab is developing CRISPR-based molecular diagnostic platforms for target amplification-free nucleic acid detection with an attomolar sensitivity via harnessing the trans-cleavage mechanism of CRISPR Cas13a and ultrasensitive electrochemical devices.
Funding sources: NSF CBET-2103025 and NSF CBET-2431020.
Representative publications:
1. Y. Zhang†, Y. Song†, Z. Weng, J. Yang, L. Avery, K. D. Dieckhaus, R. Y. Lai, X. Gao, Y. Zhang*, “A point-of-care microfluidic biosensing system for rapid and ultrasensitive nucleic acid detection from clinical samples,” Lab on a Chip 2023, 23, 3862-3873. LINK
2. Z. Weng†, Z. You†, J. Yang, N. Mohammad, M. Lin, Q. Wei, X. Gao*, Y. Zhang*, “CRISPR-Cas biochemistry and CRISPR-based molecular diagnostics”, Angew. Chem. Int. Ed. 2023, 62(17), e202214987. LINK
3. Z. Weng†, Z. You†, H. Li†, G. Wu, Y. Song, H. Sun, A. Fradlin, C. Neal-Harris, M. Lin, X. Gao*, Y. Zhang*, “CRISPR-Cas12a biosensor array for ultrasensitive detection of unamplified DNA with single-nucleotide polymorphic discrimination”, ACS Sensors 2023, 8, 4, 1489–1499. LINK
4. J. Yang†, Y. Song†, X. Deng, J. A. Vanegas, Z. You, Y. Zhang, Z. Weng, L. Avery, K. D. Dieckhaus, A. Peddi, Y. Gao*, Y. Zhang*, X. Gao*, “Engineered LwaCas13a with enhanced collateral activity for nucleic acid detection”, Nature Chemical Biology 2023, 19, 45–54. LINK
5. H. Li†, J. Yang†, G. Wu†, Z. Weng†, Y. Song, Y. Zhang, J. A. Vanegas, L. Avery, Z. Gao, H. Sun, Y. Chen, K. D. Dieckhaus, X. Gao*, Y. Zhang*, “Amplification-free detection of SARS-CoV-2 and respiratory syncytial virus using CRISPR Cas13a and graphene field-effect transistors”, Angew. Chem. Int. Ed. 2022, 61(32): e202203826. (Hot paper and selected as a back cover). LINK