title: Development of a low-volume, highly sensitive microimmunoassay using computational fluid dynamics-driven multiobjective optimization.
abstract: Immunoassays are one of the most versatile and widely performed biochemical assays and, given their selectivity and specificity, are used in both clinical and research settings. However, the high cost of reagents and relatively large sample volumes constrain the integration of immunoassays into many applications. Scaling the assay down within microfluidic devices can alleviate issues associated with reagent and sample consumption. However, in many cases a new device is designed and empirically optimized for each specific analyte, a costly and time consuming approach. In this paper, we report the development of a microfluidic bead-based immunoassay which, using antibody coated microbeads, can potentially detect any analyte or combination of analytes for which antibody coated microbeads can be generated. We also developed a computational reaction model and optimization algorithm that can be used to optimize the device for any analyte. We applied this technique to develop a low volume IL-6 immunoassay with high sensitivity (358 fM, 10 pg/mL) and a large dynamic range (4 orders of magnitude). This device design and optimization technique can be used to design assays for any protein with an available antibody and can be used with a large number of applications including biomarker discovery, temporal in vitro studies using a reduced number of cells and reagents, and analysis of scarce biological samples in animal studies and clinical research settings.
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghodbane
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kulesa
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Maguire
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Rene R
authors.initials: RR
authors.lastname: Schloss
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zahn
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, USA ; Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, 51 Blossom Street, Boston, MA, 02114, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
keywords: Computational Fluid Dynamics; Immunoassay; Microfluidic; Multi-Objective Optimization