Gold Nanoparticle Enabled Localized Surface Plasmon Resonance on Unique Gold Nanomushroom Structures for On-Chip CRISPR-Cas13a Sensing.

A novel localized surface plasmon resonance (LSPR) system based on the coupling of gold nanomushrooms (AuNMs) and gold nanoparticles (AuNPs) is developed to enable a significant plasmonic resonant shift. The AuNP size, surface chemistry, and concentration are characterized to maximize the LSPR effect. A 31 nm redshift is achieved when the AuNMs are saturated by the AuNPs. This giant redshift also increases the full width of the spectrum and is explained by the 3D finite-difference time-domain (FDTD) calculation. In addition, this LSPR substrate is packaged in a microfluidic cell and integrated with a CRISPR-Cas13a RNA detection assay for the detection of the SARS-CoV-2 RNA targets. Once activated by the target, the AuNPs are cleaved from linker probes and randomly deposited on the AuNM substrate, demonstrating a large redshift. The novel LSPR chip using AuNP as an indicator is simple, specific, isothermal, and label-free; and thus, provides a new opportunity to achieve the next generation multiplexing and sensitive molecular diagnostic system.

Effect of Functional Electrical Stimulation on Capillary Blood Flow to Muscle.

Functional electrical stimulation (FES) modifies red blood cells (RBCs) flux in blood capillaries of muscle. In this work, we aim to investigate changes in the RBC flux in small and large capillaries due to FES using zinc oxide nanowires (ZnO NWs) based electrode at different stimulation parameters. The RBC flux was significantly increased immediately after stimulation, which was evident from decreasing light intensity measured in the region of interest. Clinical Relevance- FES has numerous forms and functions. The benefit of FES is the increased blood flow to a muscle which is contracted abnormally. This work explores the use of FES to increase the blood flow and RBC flux in blood capillaries of stimulated muscle as FES generate muscle contraction and absorption.

Independent and grouped 3D cell rotation in a microfluidic device for bioimaging applications.

Cell rotation reveals important information which facilitates identification and characterization of different cells. Markedly, achieving three dimensional (3D) rolling rotation of single cells within a larger group of cells is rare among existing cell rotation techniques. In this work we present a simple biochip which can be used to trap and rotate a single cell, or to rotate multiple cells relative to each other within a group of individual red blood cells (RBCs), which is crucial for imaging cells in 3D. To achieve single RBC trapping, we employ two parallel sidewall 3D electrodes to produce a dielectrophoretic force which traps cells inside the capturing chambers of the microfluidic device, where the hydrodynamic force then induces precise rotation of the cell inside the chamber. We have also demonstrated the possibility of using the developed biochip to preconcentrate and rotate RBC clusters in 3D. As our proposed cell trapping and rotation device reduces the intricacy of cell rotation, the developed technique may have important implications for high resolution 3D cell imaging in the investigation of complex cell dynamics and interactions in moving media.

Nanophotonic-Carbohydrate Lab-on-a-Microneedle for Rapid Detection of Human Cystatin C in Finger-Prick Blood.

Miniaturized total analysis systems, for the rapid detection of disease biomarkers, with features including high biomarker sensitivity, selectivity, biocompatibility, and disposability, all at low cost are of profound importance in the healthcare sector. Within this frame of reference, we developed a lab-on-a-carbohydrate-microneedle biodevice by integrating localized surface plasmon resonance (LSPR) paper-based substrates with biocompatible microneedles of high aspect ratio (>60:1 length:width). These microneedles are completely fabricated with carbohydrate (maltose) and further coated with poly lactic-co-glycolic acid (PLGA), which together serves the purpose of fluid channels. The porous nature of PLGA, in addition to drawing blood by capillary action, filters out the whole blood, allowing only the blood plasma to reach the biorecognition layer of the developed biodevice. While the use of maltose provides biocompatibility to the microneedle, the axial compression and transverse load analysis revealed desired mechanical strength of the microneedle, with mechanical failure occurring at 11N and 9 N respectively for the compressive and transverse load. For a proof-of-principle demonstration, the developed biodevice is validated for its operational features by direct detection of cystatin C in finger-prick blood and up to a concentration of 0.01 µg/mL in buffered conditions using the LSPR technique. Furthermore, by changing the biorecognition layer, the use of the developed needle can be extended to other disease biomarkers, and therefore the innovation presented in this work represents a hallmark in the state of the art of lab-on-a-chip biodevices.

High density nanowire electrodes for intracortical microstimulation.

High-density electrodes with the nano feature size greatly enhance resolution and specificity during intracortical microstimulation. In this viewpoint, we fabricated and developed high-density nanowire (NW) electrodes, ~ 2.45×109 / cm2 that could directly stimulate specific region of the cortex with low current amplitude in the range of 120-180 µA. The proposed nanowire electrodes will help expand the capabilities of microstimulation and extend the range of dysfunctions that can be treated using microstimulation technique.

Simple and low cost integration of highly conductive three-dimensional electrodes in microfluidic devices.

This work presents a fast, simple, and cost-effective technique for fabricating and integrating highly conductive 3D microelectrodes into microfluidic devices. The 3D electrodes are made of low cost, commercially available conductive adhesive and carbon powder. The device can be fabricated by a single-step soft lithography and controllable injections of a conductive composite into microchannels. Functioning of the microfluidic device with 3D electrodes was demonstrated through DEP particle switching as an example for a wide range of microfluidic applications.

Enhanced cell viability and cell adhesion using low conductivity medium for negative dielectrophoretic cell patterning.

Negative dielectrophoretic (n-DEP) cell manipulation is an efficient way to pattern human liver cells on micro-electrode arrays. Maintaining cell viability is an important objective for this approach. This study investigates the effect of low conductivity medium and the optimally designed microchip on cell viability and cell adhesion. To explore the influence of conductivity on cell viability and cell adhesion, we have used earlier reported dielectrophoresis (DEP) buffer with a conductivity of 10.2 mS/m and three formulated media with conductivity of 9.02 (M1), 8.14 (M2), 9.55 (M3) mS/m. The earlier reported isotonic sucrose/dextrose buffer (DEP buffer) used for DEP manipulation has the drawback of poor cell adhesion and cell viability. A microchip prototype with well-defined positioning of titanium electrode arrays was designed and fabricated on a glass substrate. The gap between the radial electrodes was accurately determined to achieve good cell patterning performance. Parameters such as dimension of positioning electrode, amplitude, and frequency of voltage signal were investigated to optimize the performance of the microchip.