title: AC Electroosmosis-Enhanced Nanoplasmofluidic Detection of Ultralow-Concentration Cytokine.
abstract: Label-free, nanoparticle-based plasmonic optical biosensing, combined with device miniaturization and microarray integration, has emerged as a promising approach for rapid, multiplexed biomolecular analysis. However, limited sensitivity prevents the wide use of such integrated label-free nanoplasmonic biosensors in clinical and life science applications where low-abundance biomolecule detection is needed. Here, we present a nanoplasmofluidic device integrated with microelectrodes for rapid, label-free analysis of a low-abundance cell signaling protein, detected by AC electroosmosis-enhanced localized surface plasmon resonance (ACE-LSPR) biofunctional nanoparticle imaging. The ACE-LSPR device is constructed using both bottom-up and top-down sensor fabrication methods, allowing the seamless integration of antibody-conjugated gold nanorod (AuNR) biosensor arrays with microelectrodes on the same microfluidic platform. Applying an AC voltage to microelectrodes while scanning the scattering light intensity variation of the AuNR biosensors results in significantly enhanced biosensing performance. The AC electroosmosis (ACEO) based enhancement of the biosensor performance enables rapid (5-15 min) quantification of IL-1β, a pro-inflammatory cytokine biomarker, with a sensitivity down to 158.5 fg/mL (9.1 fM) for spiked samples in PBS and 1 pg/mL (58 fM) for diluted human serum. Together with the optimized detection sensitivity and speed, our study presents the first critical step toward the application of nanoplasmonic biosensing technology to immune status monitoring guided by low-abundance cytokine measurement.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Song
authors.affiliation: Materials Research and Education Center, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Chen
authors.forename: Meng Ting
authors.initials: MT
authors.lastname: Chung
authors.forename: Robert
authors.initials: R
authors.lastname: Nidetz
authors.forename: Younggeun
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, Tsinghua University , Beijing, 100084, People's Republic of China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Liu
authors.forename: Walker
authors.initials: W
authors.lastname: McHugh
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Cornell
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Jianping
authors.identifier: 0000-0001-9629-6739
authors.initials: J
authors.lastname: Fu
authors.forename: Katsuo
authors.identifier: 0000-0002-9613-3590
authors.initials: K
authors.lastname: Kurabayashi
mesh_terms: D015415:Biomarkers / Q000097:blood; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D016207:Cytokines / Q000097:blood*; D055664:Electrochemical Techniques / Q000295:instrumentation; D004566:Electrodes; D053841:Electroosmosis / Q000295:instrumentation*; D006046:Gold / Q000737:chemistry; D006801:Humans; D056656:Lab-On-A-Chip Devices; D057230:Limit of Detection; D036103:Nanotechnology; D043942:Nanotubes / Q000737:chemistry; D061848:Optical Imaging / Q000379:methods; D010316:Particle Size; D020349:Surface Plasmon Resonance
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006046:Gold
keywords: AC electroosmosis; Nanorod biosensor; cytokine analysis; immunoassay; localized surface plasmon resonance