E-textile based modular sEMG suit for large area level of effort analysis.

We present a novel design for an e-textile based surface electromyography (sEMG) suit that incorporates stretchable conductive textiles as electrodes and interconnects within an athletic compression garment. The fabrication and assembly approach is a facile combination of laser cutting and heat-press lamination that provides for rapid prototyping of designs in a typical research environment without need for any specialized textile or garment manufacturing equipment. The materials used are robust to wear, resilient to the high strains encountered in clothing, and can be machine laundered. The suit produces sEMG signal quality comparable to conventional adhesive electrodes, but with improved comfort, longevity, and reusability. The embedded electronics provide signal conditioning, amplification, digitization, and processing power to convert the raw EMG signals to a level-of-effort estimation for flexion and extension of the elbow and knee joints. The approach we detail herein is also expected to be extensible to a variety of other electrophysiological sensors.

Rapid capture of biomolecules from blood via stimuli-responsive elastomeric particles for acoustofluidic separation.

The detection of biomarkers in blood often requires extensive and time-consuming sample preparation to remove blood cells and concentrate the biomarker(s) of interest. We demonstrate proof-of-concept for a chip-based, acoustofluidic method that enables the rapid capture and isolation of a model protein biomarker (i.e., streptavidin) from blood for off-chip quantification. Our approach makes use of two key components - namely, soluble, thermally responsive polypeptides fused to ligands for the homogeneous capture of biomarkers from whole blood and silicone microparticles functionalized with similar, tethered, thermally responsive polypeptides. When the two components are mixed together and subjected to a mild thermal trigger, the thermally responsive moieties undergo a phase transition, causing the untethered (soluble) polypeptides to co-aggregate with the particle-bound polypeptides. The mixture is then diluted with warm buffer and injected into a microfluidic channel supporting a bulk acoustic standing wave. The biomarker-bearing particles migrate to the pressure antinodes, whereas blood cells migrate to the pressure node, leading to rapid separation with efficiencies exceeding 90% in a single pass. The biomarker-bearing particles can then be analyzed via flow cytometry, with a limit of detection of 0.75 nM for streptavidin spiked in blood plasma. Finally, by cooling the solution below the solubility temperature of the polypeptides, greater than 75% of the streptavidin is released from the microparticles, offering a unique approach for downstream analysis (e.g., sequencing or structural analysis). Overall, this methodology has promise for the detection, enrichment and analysis of some biomarkers from blood and other complex biological samples.

An acoustofluidic trap and transfer approach for organizing a high density single cell array.

We demonstrate a hybrid microfluidic system that combines fluidic trapping and acoustic switching to organize an array of single cells at high density. The fluidic trapping step is achieved by balancing the hydrodynamic resistances of three parallel channel segments forming a microfluidic trifurcation, the purpose of which was to capture single cells in a high-density array. Next, the cells were transferred into adjacent larger compartments by generating an array of streaming micro-vortices to move the cells to the desired streamlines in a massively parallel format. This approach can compartmentalize single cells with efficiencies of ≈67% in compartments that have diameters on the order of ∼100 um, which is an appropriate size for single cell proliferation studies and other single cell biochemical measurements.

Translating microfluidics: Cell separation technologies and their barriers to commercialization.

Advances in microfluidic cell sorting have revolutionized the ways in which cell-containing fluids are processed, now providing performances comparable to, or exceeding, traditional systems, but in a vastly miniaturized format. These technologies exploit a wide variety of physical phenomena to manipulate cells and fluid flow, such as magnetic traps, sound waves and flow-altering micropatterns, and they can evaluate single cells by immobilizing them onto surfaces for chemotherapeutic assessment, encapsulate cells into picoliter droplets for toxicity screenings and examine the interactions between pairs of cells in response to new, experimental drugs. However, despite the massive surge of innovation in these high-performance lab-on-a-chip devices, few have undergone successful commercialization, and no device has been translated to a widely distributed clinical commodity to date. Persistent challenges such as an increasingly saturated patent landscape as well as complex user interfaces are among several factors that may contribute to their slowed progress. In this article, we identify several of the leading microfluidic technologies for sorting cells that are poised for clinical translation; we examine the principal barriers preventing their routine clinical use; finally, we provide a prospectus to elucidate the key criteria that must be met to overcome those barriers. Once established, these tools may soon transform how clinical labs study various ailments and diseases by separating cells for downstream sequencing and enabling other forms of advanced cellular or sub-cellular analysis. © 2016 International Clinical Cytometry Society.

Magnetic separation of acoustically focused cancer cells from blood for magnetographic templating and analysis.

Liquid biopsies hold enormous promise for the next generation of medical diagnoses. At the forefront of this effort, many are seeking to capture, enumerate and analyze circulating tumor cells (CTCs) as a means to prognosticate and develop individualized treatments for cancer. Capturing these rare cells, however, represents a major engineering challenge due to their low abundance, morphology and heterogeneity. A variety of microfluidic tools have been developed to isolate CTCs from drawn blood samples; however, few of these approaches offer a means to separate and analyze cells in an integrated system. We have developed a microfluidic platform comprised of three modules that offers high throughput separation of cancer cells from blood and on-chip organization of those cells for streamlined analyses. The first module uses an acoustic standing wave to rapidly align cells in a contact-free manner. The second module then separates magnetically labeled cells from unlabeled cells, offering purities exceeding 85% for cells and 90% for binary mixtures of synthetic particles. Finally, the third module contains a spatially periodic array of microwells with underlying micromagnets to capture individual cells for on-chip analyses (e.g., staining, imaging and quantification). This array is capable of capturing with accuracies exceeding 80% for magnetically labeled cells and 95% for magnetic particles. Overall, by virtue of its holistic processing of complex biological samples, this system has promise for the isolation and evaluation of rare cancer cells and can be readily extended to address a variety of applications across single cell biology and immunology.

Magnetically Responsive Negative Acoustic Contrast Microparticles for Bioanalytical Applications.

Smart colloidal particles are routinely used as carriers for biological molecules, fluorescent reporters, cells, and other analytes for the purposes of sample preparation and detection. However, such particles are typically engineered to respond to a single type of stimulus (e.g., commercial magnetic beads to magnetic fields). Here, we demonstrate a unique class of particles that display both positive magnetic contrast and negative acoustic contrast in water. This dual functionality allows for fine spatiotemporal control, enabling multiple separation modalities and increasing the utility of the particles in various chemical and biological assays.

Fabrication and Operation of Acoustofluidic Devices Supporting Bulk Acoustic Standing Waves for Sheathless Focusing of Particles.

Acoustophoresis refers to the displacement of suspended objects in response to directional forces from sound energy. Given that the suspended objects must be smaller than the incident wavelength of sound and the width of the fluidic channels are typically tens to hundreds of micrometers across, acoustofluidic devices typically use ultrasonic waves generated from a piezoelectric transducer pulsating at high frequencies (in the megahertz range). At characteristic frequencies that depend on the geometry of the device, it is possible to induce the formation of standing waves that can focus particles along desired fluidic streamlines within a bulk flow. Here, we describe a method for the fabrication of acoustophoretic devices from common materials and clean room equipment. We show representative results for the focusing of particles with positive or negative acoustic contrast factors, which move towards the pressure nodes or antinodes of the standing waves, respectively. These devices offer enormous practical utility for precisely positioning large numbers of microscopic entities (e.g., cells) in stationary or flowing fluids for applications ranging from cytometry to assembly.