A Conductive Hydrogel Microneedle-Based Assay Integrating PEDOT:PSS and Ag-Pt Nanoparticles for Real-Time, Enzyme-Less, and Electrochemical Sensing of Glucose.

Continuous glucose meters (CGMs) have tremendously boosted diabetes care by emancipating millions of diabetic patients' need for repeated self-testing by pricking their fingers every few hours. However, CGMs still suffer from major deficiencies regarding accuracy, precision, and stability. This is mainly due to their dependency on an enzymatic detection mechanism. Here a low-cost hydrogel microneedle (HMN)-CGM assay fabricated using swellable dopamine (DA)-hyaluronic acid (HA) hydrogel for glucose interrogation in dermal interstitial fluid (ISF) is introduced. Platinum and silver nanoparticles are synthesized within the 3D porous hydrogel scaffolds for nonenzymatic electrochemical sensing of the glucose. Incorporation of a highly water dispersible conductive polymer, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) enhances the electrical properties of HMN array, making the patch suitable as the working electrode of the sensor. The in vitro and ex vivo characterization of this newly developed HMN patch is fully studied. The performance of the HMN-CGM for real-time measurement of glucose is also shown using a rat model of type 1 diabetes. The device introduces the first HMN-based assay for tracking important disease biomarkers and expect to pave the way for next generation of polymeric-based sensors.

A Conductive Hydrogel-Based Microneedle Platform for Real-Time pH Measurement in Live Animals.

Conventional microneedles (MNs) have been extensively reported and applied toward a variety of biosensing and drug delivery applications. Hydrogel forming MNs with the added ability to electrically track health conditions in real-time is an area yet to be explored. The first conductive hydrogel microneedle (HMN) electrode that is capable of on-needle pH detection with no postprocessing required is presented here. The HMN array is fabricated using a swellable dopamine (DA) conjugated hyaluronic acid (HA) hydrogel, and is embedded with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) to increase conductivity. The catechol-quinone chemistry intrinsic to DA is used to measure pH in interstitial fluid (ISF). The effect of PEDOT:PSS on the characteristics of the HMN array such as swelling capability and mechanical strength is fully studied. The HMN's capability for pH measurement is first demonstrated using porcine skin equilibrated with different pH solutions ranging from 3.5 to 9. Furthermore, the HMN-pH meter is capable of in vivo measurements with a 93% accuracy compared to a conventional pH probe meter. This HMN technology bridges the gap between traditional metallic electrochemical biosensors and the direct extraction of ISF, and introduces a platform for the development of polymeric wearable sensors capable of on-needle detection.

A microfluidic platform for drug screening in a 3D cancer microenvironment.

Development of resistance to chemotherapy treatments is a major challenge in the battle against cancer. Although a vast repertoire of chemotherapeutics is currently available for treating cancer, a technique for rapidly identifying the right drug based on the chemo-resistivity of the cancer cells is not available and it currently takes weeks to months to evaluate the response of cancer patients to a drug. A sensitive, low-cost diagnostic assay capable of rapidly evaluating the effect of a series of drugs on cancer cells can significantly change the paradigm in cancer treatment management. Integration of microfluidics and electrical sensing modality in a 3D tumour microenvironment may provide a powerful platform to tackle this issue. Here, we report a 3D microfluidic platform that could be potentially used for a real-time deterministic analysis of the success rate of a chemotherapeutic drug in less than 12h. The platform (66mm×50mm; L×W) is integrated with the microsensors (interdigitated gold electrodes with width and spacing 10µm) that can measure the change in the electrical response of cancer cells seeded in a 3D extra cellular matrix when a chemotherapeutic drug is flown next to the matrix. B16-F10 mouse melanoma, 4T1 mouse breast cancer, and DU 145 human prostate cancer cells were used as clinical models. The change in impedance magnitude on flowing chemotherapeutics drugs measured at 12h for drug-susceptible and drug tolerant breast cancer cells compared to control were 50,552±144 Ω and 28,786±233 Ω, respectively, while that of drug-susceptible melanoma cells were 40,197±222 Ω and 4069±79 Ω, respectively. In case of prostate cancer the impedance change between susceptible and resistant cells were 8971±1515 Ω and 3281±429 Ω, respectively, which demonstrated that the microfluidic platform was capable of delineating drug susceptible cells, drug tolerant, and drug resistant cells in less than 12h.

Paper microchip with a graphene-modified silver nano-composite electrode for electrical sensing of microbial pathogens.

Rapid and sensitive point-of-care diagnostics are of paramount importance for early detection of infectious diseases and timely initiation of treatment. Here, we present cellulose paper and flexible plastic chips with printed graphene-modified silver electrodes as universal point-of-care diagnostic tools for the rapid and sensitive detection of microbial pathogens or nucleic acids through utilizing electrical sensing modality and loop-mediated isothermal amplification (LAMP). We evaluated the ability of the developed paper-based assay to detect (i) viruses on cellulose-based paper microchips without implementing amplification in samples with viral loads between 106 and 108 copies per ml, and (ii) amplified HIV-1 nucleic acids in samples with viral loads between 10 fg µl-1 and 108 fg µl-1. The target HIV-1 nucleic acid was amplified using the RT-LAMP technique and detected through the electrical sensing of LAMP amplicons for a broad range of RNA concentrations between 10 fg µl-1 and 108 fg µl-1 after 40 min of amplification time. Our assay may be used for antiretroviral therapy monitoring where it meets the sensitivity requirement of the World Health Organization guidelines. Such a paper microchip assay without the amplification step may also be considered as a simple and inexpensive approach for acute HIV detection where maximum viral replication occurs.