title: PicoMolar level detection of protein biomarkers based on electronic sizing of bead aggregates: theoretical and experimental considerations.
abstract: We demonstrate a novel method for electronically detecting and quantifying protein biomarkers using microfluidic impedance cytometry. Our biosensor, which consists of gold electrodes micro-fabricated in a microchannel, detects the differences between bead aggregates of varying sizes in a micro-pore sandwiched between two micro channels. We perform a sandwich immunoassay, where the complementary antibody pairs are immobilized on two different bead types, and the presence of antigen results in bead aggregation, the amount of which depends on antigen quantity. When single beads or bead aggregates pass through the impedance sensor, differences in impedance change are detected. In this manuscript, we perform a comprehensive theoretical study on the limits imposed on sensitivity of this technique due to electronic noise and also mass transfer and reaction limits. We also experimentally characterize the performance of this technique by validating the technique on an IgG detection assay. A detection limit at the picoMolar level is demonstrated, thus comparable in sensitivity to a sandwich ELISA.
authors.affiliation: Rutgers, The State University Of New Jersey, Piscataway, NJ, 08854, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Rutgers, The State University Of New Jersey, Piscataway, NJ, 08854, USA.
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.affiliation: Rutgers, The State University Of New Jersey, Piscataway, NJ, 08854, USA.
authors.forename: P
authors.initials: P
authors.lastname: Xie
authors.affiliation: Rutgers, The State University Of New Jersey, Piscataway, NJ, 08854, USA.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Rutgers, The State University Of New Jersey, Piscataway, NJ, 08854, USA. mehdi.javanmard@rutgers.edu.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Javanmard
mesh_terms: D000906:Antibodies / Q000097:blood / Q000652:urine; D001681:Biological Assay; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D015374:Biosensing Techniques / Q000295:instrumentation*; D017097:Electric Impedance; D004566:Electrodes; D004867:Equipment Design; D006046:Gold; D006801:Humans; D057230:Limit of Detection; D044085:Microfluidics / Q000379:methods; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D015415:Biomarkers; D006046:Gold
keywords: Impedance Cytometry; Microfluidics; Protein biomarker detection