Publications by authors named "Adam Zrehen"

The advent of recombinant DNA technology fundamentally altered the drug discovery landscape, replacing traditional small-molecule drugs with protein and peptide-based biologics. Being susceptible to degradation via the oral route, biologics require comparatively invasive injections, most commonly by intravenous infusion (IV). Significant academic and industrial efforts are underway to replace IV transport with subcutaneous delivery by wearable infusion devices.

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Nanopores are single-molecule sensors capable of detecting and quantifying a broad range of unlabeled biomolecules including DNA and proteins. Nanopores' generic sensing principle has permitted the development of a vast range of biomolecular applications in genomics and proteomics, including single-molecule DNA sequencing and protein fingerprinting. Owing to their superior mechanical and electrical stability, many of the recent studies involved synthetic nanopores fabricated in thin solid-state membranes such as freestanding silicon nitride.

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Accurate identification of both abundant and rare proteins hinges on the development of single-protein sensing methods. Given the immense variation in protein expression levels in a cell, separation of proteins by weight would improve protein classification strategies. Upstream separation facilitates sample binning into smaller groups while also preventing sensor overflow, as may be caused by highly abundant proteins in cell lysates or clinical samples.

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Solid-state nanopore sensing of ultralong genomic DNA molecules has remained challenging, as the DNA must be controllably delivered by its leading end for efficient entry into the nanopore. Herein, we introduce a nanopore sensor device designed for electro-optical detection and sorting of ultralong (300+ kilobase pair) genomic DNA. The fluidic device, fabricated in-silicon and anodically bonded to glass, uses pressure-induced flow and an embedded pillar array for controllable DNA stretching and delivery.

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Plasmonic and nanopore sensors have separately received much attention for achieving single-molecule precision. A plasmonic "hotspot" confines and enhances optical excitation at the nanometer length scale sufficient to optically detect surface-analyte interactions. A nanopore biosensor actively funnels and threads analytes through a molecular-scale aperture, wherein they are interrogated by electrical or optical means.

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Solid-state nanopores (ssNPs) are extremely versatile single-molecule sensors and their potential have been established in numerous biomedical applications. However, the fabrication of ssNPs remains the main bottleneck to their widespread use. Herein, we introduce a rapid and localizable ssNPs fabrication method based on feedback-controlled optical etching.

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Herein, we introduce synchronous, real-time, electro-optical monitoring of nanopore formation by DB. Using the same principle as sub-diffraction microscopy, our nanopore localization platform based on wide-field microscopy and calcium indicators provides nanoscale sensitivity. This enables us to establish critical limitations of the fabrication process and improve its reliability.

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The existence of secondary flows in the pressure-driven flow of a concentrated suspension of noncolloidal particles through a conduit of square cross section under creeping flow conditions is confirmed experimentally. This Letter lends support to the idea that secondary currents, rather than shear-induced migration, may actually be the dominant mechanism that determines particle distribution in noncolloidal suspension flows through nonaxisymmetric geometries. This work also establishes that coextrusion of two concentrated suspensions through nonaxisymmetric geometries with a stable suspension-suspension interface is not possible, except in special situations.

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