title: Simultaneous concentration and detection of biomarkers on paper.
abstract: The lateral-flow immunoassay (LFA) is an inexpensive point-of-care (POC) paper-based diagnostic device with the potential to rapidly detect disease biomarkers in resource-poor settings. Although LFA is inexpensive, easy to use, and requires no laboratory equipment, it is limited by its sensitivity, which remains inferior to that of gold standard laboratory-based assays. Our group is the only one to have previously utilized various aqueous two-phase systems (ATPSs) to enhance LFA detection. In those studies, the sample was concentrated by an ATPS in a test tube and could only be applied to LFA after it had been extracted manually. Here, we bypass the extraction step by seamlessly integrating a polyethylene glycol-potassium phosphate ATPS with downstream LFA detection in a simple, inexpensive, power-free, and portable all-in-one diagnostic device. We discovered a new phenomenon in which the target biomarkers simultaneously concentrate as the ATPS solution flows through the paper membranes, and our device features a 3-D paper well that was designed to exploit this phenomenon. Studies with this device, which were performed at room temperature in under 25 min, demonstrated a 10-fold improvement in the detection limit of a model protein, transferrin. Our next-generation LFA technology is rapid, affordable, easy-to-use, and can be applied to existing LFA products, thereby providing a new platform for revolutionizing the current state of disease diagnosis in resource-poor settings.
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121J Engineering V, P.O. Box 951600, Los Angeles, CA 90095-1600, USA. kamei@seas.ucla.edu.
authors.forename: Ricky Y T
authors.initials: RY
authors.lastname: Chiu
authors.forename: Erik
authors.initials: E
authors.lastname: Jue
authors.forename: Allison T
authors.initials: AT
authors.lastname: Yip
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Berg
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Wang
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Kivnick
authors.forename: Phuong T
authors.initials: PT
authors.lastname: Nguyen
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kamei
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D004867:Equipment Design; D007118:Immunoassay / Q000295:instrumentation* / Q000379:methods*; D057230:Limit of Detection; D010209:Paper; D019095:Point-of-Care Systems; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D015415:Biomarkers; D011092:Polyethylene Glycols