The biomarker pipeline: Novel microfluidic instrumentation for advancing proteomic discovery to clinical diagnostics

Microfluidically-enabled tools have begun to play a role in medical diagnostics for use at the point-of-care (POC). While specifications regarding small instrument footprint, low sample volume usage, and speed of analysis make a lab-on-a-chip approach especially relevant to POC instrumentation, these operating advantages also confer significant advantages to putative biomarker validation studies. In particular, automation and enhanced reproducibility provided through fully integrated microfluidic tools provides an ideal platform for the rapid, repetitive analysis of clinical samples. The work presented details advances in an effort to streamline and improve assay operation through nascent microfluidic technologies. We have integrated core separation mechanisms (e.g., protein sizing in single percentage and gradient gels, native immunoassays) seamlessly with complex sample preparation and handling steps. A key technology enabling sophisticated analyses is incorporation of photopatterned cross-linked gels having tunable properties. This work specifically details the use of gels for rapid, on-chip protein sizing and development of native homogenous immunoassays for high-specificity measurement of proteins. The former having relevance to proteomics and biomarker validation, the latter having relevance to POC diagnostics.