Analyzing interstitial fluid (ISF) via microneedle (MN) devices enables patient health monitoring in a minimally invasive manner and in point-of-care settings. However, most MN-based diagnostic approaches require complicated fabrication processes and postprocessing of the extracted ISF or are limited to detection of electrochemically active biomarkers. Here, we show on-needle measurement of target analytes by integrating hydrogel microneedles with aptamer probes as the recognition elements. Fluorescently tagged aptamer probes are chemically attached to the hydrogel matrix using a simple and novel approach, while a cross-linked patch is formed. For reagentless detection, we employ a strand displacement strategy where fluorophore-conjugated aptamers are hybridized with a DNA competitor strand conjugated to a quencher molecule. The assay is utilized for rapid (2 min) measurement of glucose, adenosine triphosphate, L-tyrosinamide, and thrombin ex vivo. Furthermore, the system enables specific and sensitive quantification of rising and falling concentrations of glucose in an animal model of diabetes to track hypoglycemia, euglycemia, and hyperglycemia conditions. Our assay can be applied for rapid measurement of a diverse range of biomarkers, proteins, or small molecules, introducing a generalizable platform for biomolecule quantification, and has the potential to improve the quality of life of patients who are in need of close monitoring of biomarkers of health and disease.
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.
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.
Analyzing interstitial fluid (ISF) via microneedle (MN) devices enables patient health monitoring in a minimally invasive manner and at point-of-care settings. However, most MN-based diagnostic approaches require complicated fabrication processes or post-processing of the extracted ISF. Here we show in-situ and on-needle measurement of target analytes by integrating hydrogel microneedles (HMN) with aptamer probes as the target recognition elements. Fluorescently tagged aptamer probes are chemically attached to the hydrogel matrix while a crosslinked patch is formed. We use the assay for specific and sensitive quantification of glucose concentrations in an animal model of diabetes to track hypoglycemia, euglycemia, and hyperglycemia conditions. The assay can track the rising and falling concentrations of glucose and the extracted measurements closely match those from the gold standard techniques. The assay enables rapid and reagentless target detection and can be readily modified to measure other target analytes in vivo. Our system has the potential to improve the quality of life of patients who are in need of close monitoring of biomarkers of health and disease.
To enable personalized and precision medicine, it is crucial to monitor patient health status and bring information on disease-related agents and therapeutic drug molecules into the clinic. This requires new technologies to interrogate different body fluids that are rich sources of biomarkers, such as whole blood and interstitial fluid (ISF). Such technologies enable rapid, sensitive and - ultimately - real-time and continuous analysis of the clinically important biomarkers. Biophysics, materials chemistry and polymer and molecular engineering, as well as micro and nanofabrication, are crucial tools in this endeavor. At IDEATION Lab, we apply innovative engineering solutions to advance patient health monitoring using two main technologies: Microneedles and Microfluidics. In the first part of my talk, I will present our new transdermal biosensing technologies powered by engineered hydrogel microneedles (HMNs), aptamer probes, and in-situ metallic nanoparticle synthesis for minimally invasive, on-needle, and real-time measurement of clinically important biomarkers in ISF. Our HMN assays expect to pave the way for the next-generation of polymeric-based wearable biosensors. In the second part, I will discuss a real-time biosensor driven by microfluidic techniques that continuously updates specific biomolecules’ fluctuating concentration levels with picomolar sensitivity directly in whole blood. For the first time, our microfluidic assay enables measuring the dynamic changes in blood insulin which is an important knowledge gap in diabetes management. The new advances reported in this talk, enrich the level of information that can be collected from different body fluids, and provide new means and potentials for highly accurate patient health status monitoring, thus transforming the field of personalized and precision medicine.
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