Fluorescent label-free quantitative detection of nano-sized bioparticles using a pillar array

Disease diagnostics requires detection and quantification of nano-sized bioparticles including DNA, proteins, viruses, and exosomes. Here, engineers from the National University of Singapore explore a fluorescent label-free method for sensitive detection of bioparticles using a pillar array with micrometer-sized features in a deterministic lateral displacement (DLD) device. The method relies on measuring changes in size and/or electrostatic charges of 1 µm polymer beads due to the capture of target bioparticles on the surface. These changes can be sensitively detected through the lateral displacement of the beads in the DLD array, wherein the lateral shifts in the output translates to a quantitative measurement of bioparticles bound to the bead. The detection of albumin protein and nano-sized polymer vesicles with a concentration as low as 10 ng mL-1 (150 pM) and 3.75 μg mL-1, respectively, is demonstrated. This label-free method holds potential for point-of-care diagnostics, as it is low-cost, fast, sensitive, and only requires a standard laboratory microscope for detection.

DLD-based detection of bioparticles using coated micro-bead substrate

exosomes

a Adhering bioparticles on to the surface of micro-beads causing overall change in surface charge and size of bioparticle-microbead conjugates. Two mechanisms proposed to increase the apparent diameter (Dapp) for detection using b electrostatic charge repulsion depicted by the negatively charged pillars and bead, and c size increase of the bioparticle-microbead conjugate. d Shows the DLD device schematics, which can sensitively detect a lateral shift of a 10 µg mL−1 albumin coated with a mixture of uncoated 1 µm PS-COOH beads. Lateral shifts in the DLD output spectrum can be correlated to the corresponding Dapp. The black line shows the input position of the microbead sample, magenta band represents where Dapp = 350 nm (0.35 µm), and yellow band represents the maximum displaced spectrum of 1000 nm (1 µm). Scale bar is 50 µm

Zeming KK, Salafi T, Shikha S, Zhang Y. (2018) Fluorescent label-free quantitative detection of nano-sized bioparticles using a pillar array. Nat Commun 9(1):1254. [article]

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