R01EB030623

Streamlined and Comprehensive Circulating Tumor Exosome Profiling by Microfluidic Arrayed Nanoplasmonic Sensors and Actuators - Project Summary

Detection of cancer biomarkers in the blood, known as "liquid biopsy", can, in principle, improve the accuracy of measuring nearly invisible "minimal residual disease (MRD)". Exosomes are cell-excreted extracellular vesicles that contain surface proteins and genetic materials (DNA and RNA) that reflect the characteristics and makeup of the parental cell. Analyzing exosomes would therefore provide direct insight into the state of the cancerous cell.

For cancer diagnostics in particular, recent evidence has shown that several micro-RNAs are differentially expressed in CTE. Therefore, unlocking the wealth of information in CTE can potentially cause a paradigm shift. However, current barriers for profiling CTE are the following:

1. All existing technologies require blood withdrawal.
2. They involve sophisticated protocols.
3. Label-free sizing/counting lacks molecular specificity.
4. They provide highly averaged results with high background from normal exosomes, thus leading to poor sensitivity.
5. They provide "partial" information: either surface antigen or cargo DNA/RNA, but not both.

All of the above has led to a simplistic binary outcome that lacks dynamic range and cannot be used frequently with high sensitivity.

We propose a multi-pronged solution on a microfluidic arrayed nanoplasmonic sensor & actuator (MANSA) platform for:

1. Streamlined isolation, concentration, and profiling.
2. Improve sensitivity by monitoring individual unlabeled exosome binding events with dynamic imaging technology complemented by spectroscopic imaging.
3. Improve specificity by profiling both surface antigen and internal DNA/RNA biomarkers at the single exosome level.
4. Eliminate blood withdrawal using an integrated needle device.
5. Benchmark performance with various sample complexity from cancer cell line extracts to cancer patient blood samples.

Our goal is to obtain a high-resolution, digital exosome map with both multiplex surface protein and cargo DNA/RNA biomarker profiles to facilitate high dynamic range enumeration and boost sensitivity. The proposed technology will become a cost-effective, point-of-care-friendly, translational platform that will address a critical need in early cancer and MRD detection to improve cancer healthcare outcomes. The technology can also be broadly applied to exosome-based diagnostics of non-cancer diseases and basic biomedical research.

University Of Houston System

TO SUPPORT HYPOTHESIS-, DESIGN-, TECHNOLOGY-, OR DEVICE-DRIVEN RESEARCH RELATED TO THE DISCOVERY, DESIGN, DEVELOPMENT, VALIDATION, AND APPLICATION OF TECHNOLOGIES FOR BIOMEDICAL IMAGING AND BIOENGINEERING. THE PROGRAM INCLUDES BIOMATERIALS (BIOMIMETICS, BIOPROCESSING, ORGANOGENESIS, REHABILITATION, TISSUE ENGINEERING, IMPLANT SCIENCE, MATERIAL SCIENCE, INTERFACE SCIENCE, PHYSICS AND STRESS ENGINEERING, TECHNOLOGY ASSESSMENT OF MATERIALS/DEVICES), BIOSENSORS/BIOTRANSDUCERS (TECHNOLOGY DEVELOPMENT, TECHNOLOGY ASSESSMENT, DEVELOPMENT OF ALGORITHMS, TELEMETRY), NANOTECHNOLOGY (NANOSCIENCE, BIOMIMETICS, DRUG DELIVERY SYSTEMS, DRUG BIOAVAILABILITY, MICROARRAY/COMBINATORIAL TECHNOLOGY, GENETIC ENGINEERING, COMPUTER SCIENCE, TECHNOLOGY ASSESSMENT), BIOINFORMATICS (COMPUTER SCIENCE, INFORMATION SCIENCE, MATHEMATICS, BIOMECHANICS, COMPUTATIONAL MODELING AND SIMULATION, REMOTE DIAGNOSIS AND THERAPY), IMAGING DEVICE DEVELOPMENT, BIOMEDICAL IMAGING TECHNOLOGY DEVELOPMENT, IMAGE EXPLOITATION, CONTRAST AGENTS, INFORMATICS AND COMPUTER SCIENCES RELATED TO IMAGING, MOLECULAR AND CELLULAR IMAGING, BIOELECTRICS/BIOMAGNETICS, ORGAN AND WHOLE BODY IMAGING, SCREENING FOR DISEASES AND DISORDERS, AND IMAGING TECHNOLOGY ASSESSMENT AND SURGERY (TECHNIQUE DEVELOPMENT AND TECHNOLOGY DEVELOPMENT).

93.286 - Discovery and Applied Research for Technological Innovations to Improve Human Health

National Institute of Biomedical Imaging and Bioengineering (NIBIB) [HHS - NIH]

Houston, Texas 772043067 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the End Date has been extended from 03/31/25 to 03/31/26 and the total obligations have increased 350% from $678,432 to $3,052,798.