An acoustofluidic device for diagnosing preclinical Alzheimer's disease - Abstract Alzheimer’s disease (AD) is a crippling, terminal neurodegenerative illness that affects an estimated 5.5 million people in the United States and approximately 10% of the population over the age of 65. Early symptoms of the disease include impairment in recent memory, difficulties with expressive language, and behavioral changes including depressed mood. Symptoms gradually worsen over time, ultimately leading to dementia and a loss of bodily functions. Currently there is no sensitive, objective diagnostic test for the early diagnosis of AD, making it difficult for physicians to properly screen for the disease and failing to diagnose patients that may be positive for AD. While advances have been made in medical imaging for AD, they are extremely costly and have limited diagnostic accuracy. In recent years, neuron-derived exosomes (30-150 nm extracellular vesicles) have emerged as a promising biomarker for diagnosing AD. Neuron-derived exosomes found in circulation can provide a simple, non-invasive means of monitoring the health of the central nervous system. Accumulating evidence suggests that neuron-derived exosomes may play a crucial role in the pathology of AD by helping to spread abnormal, potentially disease-causing, misfolded proteins throughout the brain. Preliminary studies have shown that by analyzing the number of neuron-derived exosomes and their molecular cargo, early-stage AD patients can be distinguished from healthy controls, as well as patients with other neurological diseases. While researchers have made progress in identifying neuron-derived exosomal proteins and RNAs, difficulties surrounding the isolation and analysis of exosomes have prevented their widespread use as a biomarker for AD. Currently, there are no commercially available products capable of simultaneously isolating and analyzing neuron-derived exosomes. The objective of this SBIR project is to overcome the limitations of existing AD diagnostic technologies and address the unmet needs in the market by developing and commercializing an automated, high-purity, high-yield, biocompatible exosome isolation and accurate AD biomarker detection using acoustofluidic (i.e., the fusion of acoustics and fluid mechanics) separation and electrochemical detection technologies. During our work on the Phase I project, we successfully demonstrated the utility and feasibility of the proposed exosome isolation and analysis device for AD diagnosis by meeting or exceeding the target values for each of the four key parameters identified in the Measures of Success. In Phase II, our commercialization activities will improve the performance of the acoustofluidic chips, develop self-contained, beta-testing-ready prototypes, and validate their performance with end users. With its advantages in automation, speed, precision, and accuracy, the proposed acoustofluidic technology has the potential to greatly simplify and revolutionize the diagnosis of AD. The result will be a highly sensitive liquid biopsy that will provide a comprehensive molecular signature for AD, thus significantly improving diagnostic accuracy past existing methods and providing deeper insight in the pathophysiology of the disease.
