Genome Technology Center

Bioinstrumentation for Quantitative Biology & Medicine

Prof. Amy E. Herr
University of California, Berkeley Department of Bioengineering UCSF/UCB Joint Graduate Group in Bioengineering
https://herrlab.berkeley.edu

The ability to detect disease using molecular biomarkers could greatly reduce the toll that ailments such as heart disease and cancer exact on society. While conventional bench-top proteomic tools are central to current disease biomarker discovery and validation efforts, clinical settings would benefit tremendously from next-generation disease diagnostics having sufficient assay speed and sensitivity to rapidly measure low-abundance biomarkers in small volumes of biological fluids. This seminar will detail important advances in surmounting assay performance limitations critical to development of clinical diagnostics.

Using microfluidically-enabled design strategies, we have seamlessly integrated sample preparation and handling steps with quantitative bioanalytical assays (e.g., protein sizing, immunoassays) in a compact format. Incorporation of preparative strategies, including protein enrichment, reagent mixing, and on-line fluorescence labeling has relevance to automated assay operation. Our biomarker validation and diagnostic methods exhibit compelling sensitivity and specificity – as is relevant to complex diseases.

Periodontal disease will be presented as an instance in which disease development and progression are difficult to measure. Further, this complex disease is a case in which early detection significantly improves clinical outcomes. To measure a key mediator of periodontal disease in saliva, we have employed tunable photopatterned cross-linked gels for on-chip sample enrichment integrated with homogeneous electrophoretic immunoassays. The quantitative assays rapidly (< 10 min) report picomolar concentrations of putative biomarkers in saliva via binding of endogenous protein with fluorescently-labeled antibodies. We show that integration of preparative and analytical strategies yields significant performance advantages regarding assay reproducibility, throughput, and lossless manipulation of minute sample volumes (< microliter). This seminar will include a feasibility assessment of the diagnostic, including a retrospective investigation of periodontal disease among a pilot patient population. Mention of our efforts in protein glycoform quantitation, as regards biomarker validation and prostate cancer, will also be made.

The work presented in this seminar underscores the potential role and impact that adaptable microfluidic platforms can have on our long-term goal of accelerating progress towards molecular-level understanding and diagnosis of disease.

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