A Nanotechnology-Based Wearable Biological Sensor for Continuous Monitoring of Inflammatory Immune Diseases

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Healthcare is the field in which our modern society is witnessing rapid-paced and eye-opening technological advancements and demonstrations on a daily basis. In particular, wearable biological sensors built on a mechanically flexible substrate hold great promise to enable minimally invasive, point-of-care human health monitoring. This especially applies to those who need constant care, including bedridden and neonatal patients. However, current wearable sensors only allow for measuring a handful of physical parameters, thus lacking versatility, specificity, and often sensitivity offered by conventional biochemical techniques operated in a laboratory setting. This research aims to develop a nanotechnology-based wearable biological sensor device platform that can be attached onto the curved surface of a mouth guard and enables continuous monitoring the concentration levels of inflammatory immune disorder biomarker proteins in saliva at high accuracy, sensitivity, and specificity. This sensor platform could be eventually translated to wide clinical use to tailor the immune therapy blocking inflammation-causing agents in the body. Eliminating the long measurement lead-time and labor intensiveness that conventional clinical tests suffer from, the technology coming out of this research has the potential to provide the means to precisely monitor the immune status of an individual person, which meets the urgent need for 'Precision (or Personalized) Medicine' curing systemic immune disorders. In this program, the principal investigators (PIs) will collaborate with the Ecotek lab's Young Xplorer program in order to offer after-school hands-on research experiences in sensor nanofabrication to K-12 students. This program will allow the PIs to participate in conferences organized by Science-Technology-Engineering-Mathematics (STEM) societies, such as Society of Hispanic Professional Engineers (SHPE), Advancing Hispanics, Chicanos, and Native Americans in Science (SANCAS) Society, and Society of Women Engineers (SWE), to stimulate the interests of underrepresented minority students in nanotechnology-based biological sensor devices and solicit their participation in the Summer Research Opportunities Program (SROP) hosted by the PIs. Cytokines are key biomolecules acting as mediators and modulators of the complex functional interactions and responses of the immune system. Quantifying cytokines allows immune responses to be monitored, providing clinically and immunologically useful information related to infectious diseases, cancer, autoimmune diseases, allergy transplantation, and drug discovery. The goal of this research is to establish an integrated device technology that enables continuous monitoring of the immune status by using a wearable label-free cytokine biological sensor. With the proposed study completed, this research will establish nanoscale device fabrication techniques required for strategically integrating structurally uniform, high-density nanoplasmonic biological sensor arrays and an atomically thin semiconducting photodetector device layer onto a mechanically flexible common microsystem platform. It will also provide fundamental device physics knowledge critically important to maximize sensor integrability, sensitivity, response speed, analyte detectability, biological/photo signal transduction efficiency, and versatility of the device under mechanical deformations on a curved surface. The unique biosensing scheme used for the fully flexible device employs (1) biologically tuned nanoplasmonic light absorbance resonance shifts and (2) high-responsivity, high-quantum-efficiency photoelectronic conversion by two-dimensional semiconducting transition metal dichalcogenide (TMDC) structures. As a result, the proposed device is expected to enable label-free, continuous, concurrent, minimally-invasive detection of 4 key salivary cytokine biomarkers at unprecedented levels of detectability (limit-of-detection (LOD) 1 pg/mL ~ 50fM) and response speed ( 10 min) in point-of-care settings. This sensor response speed is equivalent to a total assay time more than 20-100 times shorter than that of the conventional gold standard clinical test. This research holds great promise to develop the first wearable photoelectronic biological sensor technology based on the analyte-receptor binding immunoassay mechanism, which is broadly applicable to detection of a wide variety of protein disease markers.