Protein glycosylation is ubiquitously involved in all domains of life and holds the key to elucidating molecular mechanisms underpinning disease. Despite the biomedical and clinical significance of glycans, progress in glycomics has considerably lagged behind genomics and proteomics, owing to enormous structural diversity and dynamic alternation of glycans arising from complex non-template driven biosynthesis. Thus it is imperative to develop innovative technologies and instrumentation that can catalyze key breakthroughs in glycomic analysis. This proposal intends to address the urgent need of the next-generation glycomics technologies by leveraging on new microfluidic platforms stemming from research in the PI's laboratory. Specifically, the PI proposes to develop a novel microfluidic actuator-based single-molecule analysis method that can substantially improve the analytical performance of lectin microarray. Moreover, the PI seeks to integrate sample processing functionalities with the digital lectin-antibody barcode array system to construct a ?sample-in-answer-out? digital microfluidic lectin array platform for sensitive and quantitative targeted glycomic profiling in a high-throughput manner. The project consists of three aims: 1) develop a digital microfluidic approach for single-molecule quantification of low-abundance glycoproteins; 2) develop a fully integrated microsystem for multiplexed, quantitative targeted glycomic profiling; and 3) demonstrate quantitative comparative glycomic profiling of plasma from ovarian cancer patients. This research, if successful, will yield a key transformative tool for systems glycomics and allow the PI to pursue the long-term interest in biomedical investigation of pathological roles of protein glycosylation through obtaining dynamic overview of human plasma glycome.
(RELEVANCE) Protein post-translational modification by carbohydrates (glycosylation) is ubiquitously involved in many life- threatening diseases, such as cancer. The proposed work aims to develop a new biomedical microsystem that can catalyze breakthroughs in elucidating the pathological roles of protein glycosylation and in developing reliable biomarkers for early diagnosis and better treatment of disease. The microsystem is also adaptable for potential use in the point-of-care and clinical settings.
| Zhang, Peng; Crow, Jennifer; Lella, Divya et al. (2018) Ultrasensitive quantification of tumor mRNAs in extracellular vesicles with an integrated microfluidic digital analysis chip. Lab Chip 18:3790-3801 |
| Zhang, Peng; Samuel, Glenson; Crow, Jennifer et al. (2018) Molecular assessment of circulating exosomes toward liquid biopsy diagnosis of Ewing sarcoma family of tumors. Transl Res 201:136-153 |
| Yang, Yang; Zeng, Yong (2018) Microfluidic communicating vessel chip for expedited and automated immunomagnetic assays. Lab Chip 18:3830-3839 |
| Shang, Yuqin; Zeng, Yun; Zeng, Yong (2016) Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling. Sci Rep 6:20297 |
