The enzyme-linked immunoassay (ELISA) is an assay technology that is ubiquitous but nevertheless has limited sensitivity due to nonspecific binding and background noise. To enable more sensitive biomarker detection than ELISA in a shorter time, we have developed simple fluidic systems in conjunction with smart polymer technologies[1, 2, 3, 4]. One such system purifies and concentrates the malarial antigen Plasmodium falciparum histidine-rich protein 2 (PfHRP2) from human plasma via the capture and triggered release of anti-PfHRP2 antibodies conjugated with a temperature-responsive polymer. This capture and release occurs at porous membranes grafted with the same polymer. The PfHRP2 antigen can be processed and detected at clinically relevant concentrations in less than 30 minutes[4]. Similarly, we developed a microreactor that rapidly purifies and enriches prostate-specific antigen (PSA), a prostate cancer biomarker, from human plasma within 30 minutes[1], enabling PSA detection with much high sensitivity than with ELISA: the limit of detection (LOD) was two orders of magnitude lower than that of ELISA. This microreactor employs anti-PSA antibodies conjugated with a temperature-responsive polymer, and capture and release occur at channel surfaces grafted with the same polymer. The desired PSA concentration was achieved by continuously flowing these conjugates into the heated recirculator, which allowed nearly linear PSA enrichment with increasing specimen volume[1, 3].
Hoffman JM, Stayton PS, Hoffman AS, Lai JJ. A Stimuli-Responsive Reagent System for Enabling Microfluidic Immunoassays with Biomarker Purification and Enrichment. Bioconjugate chemistry. 2014.
Ebara M, Hoffman JM, Hoffman AS, Stayton PS, Lai JJ. A Photoinduced Nanoparticle Separation in Microchannels via pH-Sensitive Surface Traps. Langmuir. 2013;29(18):5388-93.
Hoffman JM, Ebara M, Lai JJ, Hoffman AS, Folch A, Stayton PS. A helical flow, circular microreactor for separating and enriching “smart” polymer–antibody capture reagents. Lab on a Chip. 2010;10(22):3130-8.
Golden AL, Battrell CF, Pennell S, Hoffman AS, J. Lai J, Stayton PS. Simple fluidic system for purifying and concentrating diagnostic biomarkers using stimuli-responsive antibody conjugates and membranes. Bioconjugate chemistry. 2010;21(10):1820-6.