Research overview
Analytical Science & Engineering
Better understanding of molecular mechanisms underlying disease increasingly demands the development of new enabling analytical technologies to probe enormously complex molecular interactions involved in disease, such as cancer. Microfluidics promises the development of new technologies capable of quantitative molecular and cellular analyses with better sensitivity, specificity, spatial and temporal resolution, and throughput. In addition, nanomaterials offer immense opportunities for biosensing due to their unique chemical and physical properties. We are interested in exploring the synergistic combination of microfluidics, nanomaterials, and biomolecular assays to develop transformative bioanalytical technologies that enable high-performance analysis of biomolecules, such as proteins, mRNAs and microRNAs. For instance, we are exploring new concepts of digital chemistry to develop single-molecule and single-cell analysis technologies. The applications of these new ultrasensitive analytical technologies will be focused on quantitative analysis of rare molecular events and critical biological pathways relevant to cellular functions, disease pathology, clinical diagnostics and therapeutics.
P. Zhang, X. Zhou, M. He, Y. Shang, A.L. Tetlow, A.K. Godwin, Y. Zeng, “Ultrasensitive Detection of Circulating Exosomes with a 3D-Nanopatterned Microfluidic Chip”, Nat Biomed Eng, 2019, 3, 438–451.
H. Cao, X. Zhou, Y. Zeng, “Microfluidic Exponential Rolling Circle Amplification for Rapid and Ultrasensitive microRNA Detection Directly from Biological Samples”, Sensor Actuat B-Chem, 2019, 279, 447-457.
X. Zhou, G.C. Ravichandran, P. Zhang, Y. Zeng, “A Microfluidic Alternating-Pull-Push Active Digitization Method for Reproducible Sample-Loss-Free Digital PCR”, Lab Chip, 2019, 19, 4104-4116.
Extracellular Vesicles
Liquid biopsy promises to capture a global view of tumor dynamics, as opposed to tissue biopsy that provides a localized snapshot of tumor. Most eukaryotic cells release membranous extracellular vesicles (EVs) including exosomes derived from the endolysosomal pathway with a size range of ~30-150 nm. EVs play important biological roles via transfer of a subset of molecules, e.g., proteins, RNAs, and lipids, from parent cells. The constitutive release of EVs with selectively enriched biomolecules presents distinctive opportunities for probing tumor biology in a non-invasive manner. However, the biology of EVs remains largely undetermined, due in part to the challenges in EV isolation and molecular analysis. Our research aims to adapt the novel nanomaterials and microfluidics-based assays to efficient isolation and quantitative molecular profiling of exosome-like EVs in cancer. Using cell lines and human specimen, the genomic and proteomic landscape of EV cargo will be characterized in the context of modulating the cellular processes underlying tumorigenesis, evolution, and metastasis to better understand their functional roles and potential clinical values.
Representative publications:
H. Yan, Y. Li, S. Cheng, Y. Zeng*, “Advance in Analytical Technologies for Extracellular Vesicles”, Analytical Chemistry, 2021, in press (Invited Review).
P. Zhang, X. Wu, G. Gardashova, Y. Yang, Y. Zhang, L. Xu, Y. Zeng, “Molecular and Functional Analysis of Circulating Exosomes Using Nano-engineered Microchips Monitor Tumor Progression and Metastasis”, Sci Transl Med, 2020, 12, eaaz2878.
P. Zhang, J. Crow, D. Lella, X. Zhou, G. Samuel, A.K. Godwin, Y. Zeng, “Ultrasensitive Quantification of Tumor mRNAs in Extracellular Vesicles with Integrated Microfluidic Digital Analysis Chip”. Lab Chip, 2018, 18, 3790-3801.
Biomedical Glycoproteomics & Glycomics
Protein glycosylation is ubiquitously involved in all aspects of tumor development. While glycoproteins and their carbohydrate modifications (glycans) show great potential for cancer diagnosis and prognosis, progress of glycobiology and clinical utility has been largely hindered due to the complexity of glycome, dynamic nature of glycosylation changes, and the lack of efficient analytical tools. In response to these challenges, our group is interested in exploiting microfluidic platforms to leverage the performance of glycoproteomic and glycomic analysis. Our short-term goal is to develop high-throughput glycomic profiling technologies that enable sensitive quantitation of glycoproteins of interest, structural analysis of glycans, and dynamic mapping of disease-associated glycosylation aberrations using minute blood samples. With cross-disciplinary collaborations, we aim to address the long-term goal– development and clinical validation of glyco-biomarkers and diagnostic devices for early detection of cancer and cancer risk.
Y. Shang, Y, Zeng, Y. Zeng, “Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling”, Sci Rep, 2016, 6, 20297.
Shang, Y.; Zeng, Y. “Focused Glycomic Profiling with an Integrated Microfluidic Lectin Barcode System” Methods in Enzymology, 2018; 598, 169-196.
Liquid Biopsy-Based Diagnostics
Currently most cancers are diagnosed at late stages when the disease has become unresectable and incurable. Developing non-invasive blood-based tests is extremely appealing for presymptomatic screening and early detection of cancers where obtaining tissue biopsy is highly invasive and costly. Probing circulating exosomes becomes an emerging liquid biopsy paradigm for cancer detection and monitoring response to treatment. We are passionate about translating our technologies and knowledge into the advance in precision diagnosis and medicine. We are developing new liquid biopsy diagnostics approaches that integrate molecular and functional EV profiles, nanochip technology and machine learning algorithm. IN collaboration with biologist and clinician, we are working on the assessment and pre-clinical validation of the EV-based platforms for early diagnosis and monitoring in several different types of cancer and Alzheimer’s Disease.
P. Zhang, X. Wu, G. Gardashova, Y. Yang, Y. Zhang, L. Xu, Y. Zeng, “Molecular and Functional Analysis of Circulating Exosomes Using Nano-engineered Microchips Monitor Tumor Progression and Metastasis”, Sci Transl Med, 2020, 12, eaaz2878.
Z. Zhao, Y. Yang, Y. Zeng, M. He, “A Microfluidic ExoSearch Device for Multiplexed Exosome Detection Towards Blood-based Ovarian Cancer Diagnosis”, Lab Chip, 2016, 16, 489 – 496.
P. Zhang, G. Samuel, J. Crow, A.K. Godwin, Y. Zeng, “Molecular Assessment of Circulating Exosomes towards Liquid Biopsy Diagnosis of Ewing Sarcoma Family of Tumors” Transl. Res., 2018, 201, 136-153.
Funding
