title: A simple microfluidic aggregation analyzer for the specific, sensitive and multiplexed quantification of proteins in a serum environment.
abstract: Portable and low-cost platforms for protein biomarker detection are highly sought after for point of care applications. We demonstrate a simple microfluidic device for the rapid, electrically-based detection of proteins in serum. Our aggregation analyzer relies on detecting the protein-induced aggregation of sub-micron particles, using a one-step procedure followed by a fast, particle-by-particle measurement with a very high count rate. This enables the rapid and precise quantification of C-Reactive protein levels, within the clinically relevant range, using unprocessed human serum and a disposable microfluidic device; no optics are involved in the implementation. Due to the single particle detection format and the use of microfluidics, only a small volume of serum (~50 nL) is needed to complete the analysis. The method can be easily extended to multiplexed biomarker detection by combining an assay using differently sized particles, each targeting a separate protein. We illustrate this by using two sizes of latex beads and demonstrating the simultaneous detection of two different proteins in a serum environment with minimal cross-interference. This confirms that our aggregation analyzer platform provides a simple and straightforward method for multiplexed biomarker detection in a low cost, portable design.
authors.affiliation: Department of Physics, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Rajan
authors.affiliation: HGST Western Digital, San Jose Research Center, San Jose, CA 95138, USA.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Rajauria
authors.affiliation: Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Ray
authors.affiliation: Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Sumita
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA. Electronic address: anc@uchicago.edu.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Cleland
mesh_terms: D001774:Blood Chemical Analysis / Q000295:instrumentation*; D001798:Blood Proteins / Q000032:analysis*; D045424:Complex Mixtures / Q000097:blood*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation*; D056656:Lab-On-A-Chip Devices; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001798:Blood Proteins; D045424:Complex Mixtures
keywords: Lab-on-chip; Label-free biosensing; Microfluidics; Particle immunoassay; Resistive pulse sensing