Tunable Picoliter-Scale Dropicle Formation Using Amphiphilic Microparticles with Patterned Hydrophilic Patches.

Microparticle-templated droplets or dropicles have recently gained interest in the fields of diagnostic immunoassays, single-cell analysis, and digital molecular biology. Amphiphilic particles have been shown to spontaneously capture aqueous droplets within their cavities upon mixing with an immiscible oil phase, where each particle templates a single droplet. Here, an amphiphilic microparticle with four discrete hydrophilic patches embedded at the inner corners of a square-shaped hydrophobic outer ring of the particle (4C particle) is fabricated.

Amphiphilic Particle-Stabilized Nanoliter Droplet Reactors with a Multimodal Portable Reader for Distributive Biomarker Quantification.

Compartmentalization, leveraging microfluidics, enables highly sensitive assays, but the requirement for significant infrastructure for their design, build, and operation limits access. Multimaterial particle-based technologies thermodynamically stabilize monodisperse droplets as individual reaction compartments with simple liquid handling steps, precluding the need for expensive microfluidic equipment. Here, we further improve the accessibility of this lab on a particle technology to resource-limited settings by combining this assay system with a portable multimodal reader, thus enabling nanoliter droplet assays in an accessible platform.

Sensitizing drug-resistant cancer cells from blood using microfluidic electroporator.

Direct assessment of patient samples holds unprecedented potential in the treatment of cancer. Circulating tumor cells (CTCs) in liquid biopsies are a rapidly evolving source of primary cells in the clinic and are ideal candidates for functional assays to uncover real-time tumor information in real-time. However, a lack of routines allowing direct and active interrogation of CTCs directly from liquid biopsy samples represents a bottleneck for the translational use of liquid biopsies in clinical settings.

Engineering Design of Concentric Amphiphilic Microparticles for Spontaneous Formation of Picoliter to Nanoliter Droplet Volumes.

Simple mixing of aqueous and oil solutions with amphiphilic particles leads to the spontaneous formation of uniform reaction volumes (dropicles) that can enable numerous applications in the analysis of biological entities (e.g., cells and molecules).

Monodisperse drops templated by 3D-structured microparticles.

The ability to create uniform subnanoliter compartments using microfluidic control has enabled new approaches for analysis of single cells and molecules. However, specialized instruments or expertise has been required, slowing the adoption of these cutting-edge applications. Here, we show that three dimensional-structured microparticles with sculpted surface chemistries template uniformly sized aqueous drops when simply mixed with two immiscible fluid phases.

A review of biosensor technologies for blood biomarkers toward monitoring cardiovascular diseases at the point-of-care.

Cardiovascular diseases (CVDs) cause significant mortality globally. Notably, CVDs disproportionately negatively impact underserved populations, such as those that are economically disadvantaged and often located in remote regions. Devices to measure cardiac biomarkers have traditionally been focused on large instruments in a central laboratory but the development of affordable, portable devices that measure multiple cardiac biomarkers at the point-of-care (POC) are needed to improve clinical outcomes for patients, especially in underserved populations.

Fabrication of 3D concentric amphiphilic microparticles to form uniform nanoliter reaction volumes for amplified affinity assays.

Reactions performed in uniform microscale volumes have enabled numerous applications in the analysis of rare entities (e.g. cells and molecules).

Computational cytometer based on magnetically modulated coherent imaging and deep learning.

Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D).

Nanoplasmonic swarm biosensing using single nanoparticle colorimetry.

We demonstrate a swarm biosensing platform that detects analyte based on the change in plasmonic signal from thousands of single nanoparticles sensors, leading to increased quantitative accuracy. Following dark field microscopy, we perform computational image registration and analyses to compile the hue change from thousands of single gold nanoparticles acting as individual quantitative biosensors. This platform demonstrated a limit of detection of 10 pM with a dynamic range of at least 4 orders of magnitude in buffer solution, and the successful detection of c-reactive protein (CRP) in serum compatible with 3-tier clinical cutoffs within a 10-fold difference without the need for a blocking step.

Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System.

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology.

Direct drug cocktail analyses using microscale vortex-assisted electroporation.

Combination therapy has become one of the leading approaches for treating complex diseases because it coadministers clinically proven drugs to concurrently target multiple signaling pathways of diseased cells. Identification of synergic drug combinations at their respective effective doses without unwanted accumulative side effects is the key to success for such therapy. In this work, we demonstrate the feasibility of the vortex-assisted microfluidic electroporation system for direct drug cocktail analyses where drug substances were individually delivered into cytosols in a sequential and dosage-controlled manner.

Inducing self-rotation of cells with natural and artificial melanin in a linearly polarized alternating current electric field.

The phenomenon of self-rotation observed in naturally and artificially pigmented cells under an applied linearly polarized alternating current (non-rotating) electrical field has been investigated. The repeatable and controllable rotation speeds of the cells were quantified and their dependence on dielectrophoretic parameters such as frequency, voltage, and waveform was studied. Moreover, the rotation behavior of the pigmented cells with different melanin content was compared to quantify the correlation between self-rotation and the presence of melanin.

An AC electrokinetics facilitated biosensor cassette for rapid pathogen identification.

To develop a portable point-of-care system based on biosensors for common infectious diseases such as urinary tract infection, the sensing process needs to be implemented within an enclosed fluidic system. On chip sample preparation of clinical samples remains a significant obstacle to achieving robust sensor performance. Herein AC electrokinetics is applied in an electrochemical biosensor cassette to enhance molecular convection and hybridization efficiency through electrokinetics induced fluid motion and Joule heating induced temperature elevation.

Automated rotation rate tracking of pigmented cells by a customized block-matching algorithm.

This article describes an automated rotation rate tracking algorithm for pigmented cells that undergo rotation in a dielectrophoretic (DEP) force field. In a completely automated process, we preprocess each frame of a video sequence, then analyze the sequence frame by frame using a rotating-circle template with a block-matching algorithm, and finally estimate the rotation rate of the pigmented cells using a pixel-patch correlation. The algorithm has been demonstrated to accurately calculate the DEP-induced rotation rate of the cell up to 250 rpm.