Abstract
Disease diagnostics requires detection and quantification of nano-sized bioparticles including DNA, proteins, viruses, and exosomes. Here, a fluorescent label-free method for sensitive detection of bioparticles is explored 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.
Highlights
Disease diagnostics requires detection and quantification of nano-sized bioparticles including DNA, proteins, viruses, and exosomes
The deterministic lateral displacement (DLD) segment used for this capture had a gap of 4 μm and gradient of 0.75° resulting in a DLD cut-off size (Dc) of 700 nm and the interaction between 1 μm particle and the DLD pillar is ensured
Using albumin and polymer vesicle as proof of concept, we demonstrated a fluorescent label-free method for detection of nano-sized albumin proteins and vesicles using a PDMS DLD pillar array with micrometer-sized features
Summary
Disease diagnostics requires detection and quantification of nano-sized bioparticles including DNA, proteins, viruses, and exosomes. A fluorescent label-free method for sensitive detection of bioparticles is explored using a pillar array with micrometer-sized features in a deterministic lateral displacement (DLD) device. The biosensor tracks changes in biophysical interactions of binding events, mass changes, refractive index or chemical reactions, and transduces the information as mechanical, electrical, or optical signals, and have shown detection of proteins down to femtomolar levels These techniques often require precision engineering of nano-features, complex optical setups, secondary antibodies in sandwich assays, novel nanoprobes (e.g., graphene oxide, carbon nanotubes, and gold nanorods) or additional amplification step such as aggregation of nanoparticles to reduce the limit of detection (LOD)[11]. A fluorescent label-free method for sensitive detection of nano-sized proteins and polymer vesicles using a DLD pillar array with micrometer-sized features is demonstrated. We pushed the boundaries of DLD and applied our model for fluorescent label-free detection of nano-sized proteins and polymer vesicles, which open opportunities for low-cost medical diagnosis, liquid biopsy, and detection of biologically relevant DNA, RNA, exosomes, viruses, and proteins
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