Engineering approaches for point-of-care diagnosis of inner ear disorders based on the detection of blood biomarkers

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Permanent damage to the inner ear cells leads to hearing and balance disorders. There is no diagnostic test available to identify the exact location of cellular damage in the inner ear. Thus, the need for new diagnostic methods based on the detection of inner ear circulating blood biomarkers is unmet. In the proposed research, we aim to develop for the first time, point-of-care (POC) biosensor platforms for the rapid detection and quantification of inner ear blood biomarkers including specific cells, genes, antibodies, or proteins. We will explore the uncharacterized attributes of the POC diagnostic platform for the identified inner ear biomarkers throughout the development of biomarker recognition strategies such as antibody, peptide, or aptamer-based conjugation mechanisms for specific target capturing, design of single-step assays for rapid ultra-sensitive electrochemical detection of the target biomarkers in blood, (3) portable disposable paper device prototype for detection of multiple target blood biomarkers at low concentration in small sample-volumes. The long-term objective of this proposal is to build a comprehensive diagnostic platform for the inner ear and beyond. Recent reports indicated few inner ear protein biomarkers, such as serum prestin and otolin-1 as indicators of inner ear disorders. However, the detection methods for accurately measuring these proteins are based on the conventional multi-step time-consuming quantification processes. We will design electrochemical biosensors to achieve high levels of sensitivity, signal selectivity, and rapidness with the ease of calibration. We will implement the surface-immobilized assays that are compatible with real samples to achieve the target selectivity through DNA hybridization, antibody conjugation, or protein-protein interactions. In addition, with the design of high-curvature nanostructured electrodes with large surface areas, we aim to improve the detection limits in small sample volumes. Furthermore, top-down and bottom-up approaches will be used to develop various microfluidic substrates made of glass or paper with addressable channels and electrodes. We will conduct our research using molecular synthesis and conjugation techniques, electrochemical fabrication and printing techniques, as well as characterization methods. Ultimately, more accurate diagnostics through the detection of blood biomarkers will help identify the sites of damage in the inner ear - sensory hair cells, auditory neurons, etc. This will provide the ability to diagnose and monitor the occurrence and progression of a variety of inner ear disorders as well as the efficacy of treatment. While the initial design of the POC biosensing platform is for the detection of inner ear protein biomarkers, several clinically relevant circumstances would benefit from such an approach for the rapid early-stage diagnosis.