Microbial community interactions on a chip.

Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological interactions within these communities can affect the survival of individual members and the entire community. However, the prohibitively high number of possible interactions within a microbial community has made the characterization of factors that influence community development challenging.

Griddient: a microfluidic array to generate reconfigurable gradients on-demand for spatial biology applications.

Biological tissues are highly organized structures where spatial-temporal gradients (e.g., nutrients, hypoxia, cytokines) modulate multiple physiological and pathological processes including inflammation, tissue regeneration, embryogenesis, and cancer progression.

Microfluidic device with reconfigurable spatial temporal gradients reveals plastic astrocyte response to stroke and reperfusion.

As a leading cause of mortality and morbidity, stroke constitutes a significant global health burden. Ischemic stroke accounts for 80% of cases and occurs due to an arterial thrombus, which impedes cerebral blood flow and rapidly leads to cell death. As the most abundant cell type within the central nervous system, astrocytes play a critical role within the injured brain.

SEEMLIS: a flexible semi-automated method for enrichment of methylated DNA from low-input samples.

Background: DNA methylation alterations have emerged as hallmarks of cancer and have been proposed as screening, prognostic, and predictive biomarkers. Traditional approaches for methylation analysis have relied on bisulfite conversion of DNA, which can damage DNA and is not suitable for targeted gene analysis in low-input samples. Here, we have adapted methyl-CpG-binding domain protein 2 (MBD2)-based DNA enrichment for use on a semi-automated exclusion-based sample preparation (ESP) platform for robust and scalable enrichment of methylated DNA from low-input samples, called SEEMLIS.

Volumeless reagent delivery: a liquid handling method for adding reagents to microscale droplets without increasing volume.

The addition of reagents for assays in digital microfluidic (DMF) systems is traditionally done by merging of droplets containing different analytes or reagents in solution. However, this process significantly increases droplet volume after each step, resulting in dilution of the analyte and reagents. Here, we report a new technique for performing reagent additions to aqueous droplets without significantly increasing the droplet's volume: volume-less reagent delivery (VRD).

Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2.

The COVID-19 pandemic exposed difficulties in scaling current quantitative PCR (qPCR)-based diagnostic methodologies for large-scale infectious disease testing. Bottlenecks include lengthy multi-step processes for nucleic acid extraction followed by qPCR readouts, which require costly instrumentation and infrastructure, as well as reagent and plastic consumable shortages stemming from supply chain constraints. Here we report an Oil Immersed Lossless Total Analysis System (OIL-TAS), which integrates RNA extraction and detection onto a single device that is simple, rapid, cost effective, and requires minimal supplies and infrastructure to perform.

Fluorescence "Turn-on" Lectin Sensors Fabricated by Ligand-Assisted Labeling Probes for Detecting Protein-Glycoprotein Interactions.

Elucidation of protein-protein interactions (PPIs) is often very challenging and yields complex and unclear results. Lectin-glycoprotein interactions are especially difficult to study due to the noncovalent nature of the interactions and inherently low binding affinities of proteins to glycan ligands on glycoproteins. Here, we report a "ligand-directed labeling probe (LLP)"-based approach to fabricate protein probes for elucidating protein-glycoprotein interactions.

Centrifugation-Assisted Immiscible Fluid Filtration for Dual-Bioanalyte Extraction.

The extraction of bioanalytes is the first step in many diagnostic and analytical assays. However, most bioanalyte extraction methods require extensive dilution-based washing processes that are not only time-consuming and laborious but can also result in significant sample loss, limiting their applications in rare sample analyses. Here, we present a method that enables the efficient extraction of multiple different bioanalytes from rare samples (down to 10 cells) without washing-centrifugation-assisted immiscible fluid filtration (CIFF).

Automated System for Small-Population Single-Particle Processing Enabled by Exclusive Liquid Repellency.

Exclusive liquid repellency (ELR) describes an extreme wettability phenomenon in which a liquid phase droplet is completely repelled from a solid phase when exposed to a secondary immiscible liquid phase. Earlier, we developed a multi-liquid-phase open microfluidic (or underoil) system based on ELR to facilitate rare-cell culture and single-cell processing. The ELR system can allow for the handling of small volumes of liquid droplets with ultra-low sample loss and biofouling, which makes it an attractive platform for biological applications that require lossless manipulation of rare cellular samples (especially for a limited sample size in the range of a few hundred to a few thousand cells).

Double-exclusive liquid repellency (double-ELR): an enabling technology for rare phenotype analysis.

Double-exclusive liquid repellency (double-ELR) is an extreme wettability phenomenon in which adjacent regions selectively and completely repel immiscible liquids with different surface chemistries on a non-textured substrate (i.e., a substrate in absence of micro/nano-structures).

Proton-ELISA: Electrochemical immunoassay on a dual-gated ISFET array.

Here we report an electrochemical immunoassay platform called Proton-ELISA (H-ELISA) for the detection of bioanalytes. H-ELISA uniquely utilizes protons as an immunoassay detection medium, generated by the enzyme glucose oxidase (GOx) coupled with Fenton's reagent in a proton amplification reaction cascade that results in a highly amplified signal. A proton-sensitive dual-gated ion-sensitive field effect transistor (DG-ISFET) sensor was also developed for sensitive and accurate detection of the proton signal in H-ELISA.

Fabrication of a protein microarray by fluorous-fluorous interactions.

Fluorous-modified surfaces have emerged as a powerful tool for the immobilization of fluorous-tagged biomolecules based on their specificity and the strength of fluorous-fluorous interactions. To fabricate a fluorous-based protein microarray, we designed two strategies for site-specific modification of proteins with a fluorous tag: attaching the fluorous tag to the C-termini of expressed proteins by native chemical ligation (NCL) or to the Fc domain of antibodies through boronic acid (BA)-diol interactions. The perfluoro-tagged proteins could be easily purified by fluorous-functionalized magnetic nanoparticles (MNPs) and immobilized on a fluorous chip with minimal non-specific adsorption.

Self-concentrating buoyant glass microbubbles for high sensitivity immunoassays.

Here, we report the novel application of a material with self-concentrating properties for enhancing the sensitivity of immunoassays. Termed as glass microbubbles, they are antibody functionalized buoyant hollow glass microspheres that simultaneously float and concentrate into a dense monolayer when dispensed in a liquid droplet. This self-concentrating charactaristic of the microbubbles allow for autonomous signal localization, which translates to a higher sensitivity compared to other microparticle-based immunoassays.