# Exosome separation and digital resolution detection of blood-based nucleic acid biomarkers for noninvasive therapeutic diagnostics in cancer

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $556,370

## Abstract

Abstract
 Multiple drug therapies have been approved for treating advanced cancer. However, the effectiveness of
each is variable and the ability to monitor or predict efficacy in individual patients is underdeveloped. Our team
recently demonstrated (using traditional sequencing-based methods) that expression levels of specific
microRNAs (miRNAs) in blood can effectively predict treatment outcomes. The goal of this proposal is to develop
innovative technologies that will allow us to measure miRNAs from a patient on a frequent basis, in a way that
is convenient and rapid, to enable precise adjustment of therapy. This is currently not achievable using RT-PCR
or sequencing-based detection. All cancers are associated with heterogeneous somatic genetic alterations,
ushering in a new generation of nucleic-acid-based targeted treatments. The measurement of somatic genome
based biomarkers to assess, monitor, and change treatments is needed. Circulating exosomal miRNAs
represent one class of highly specific markers of cancer-associated genetic mutations that can be noninvasively
sampled from blood, whose quantitation can provide previously-unavailable information to clinicians for
generating informed decisions on selection of effective treatments among the wide array of options. In order to
make effective routine use of miRNA cancer biomarkers, novel technical approaches will need to be developed
that can offer a high degree of multiplexing, quantitation, ultrasensitivity, low cost, simplicity, integrated sample
processing, and robust instrumentation suitable for point of care (POC) settings.
 We link a newly demonstrated form of microscopy, called NanoParticle Photonic Resonator Absorption
Microscopy (NP-PRAM) with a simple and effective exosome isolation approach to perform sample preparation
that yields exosomal miRNA for detection. Using plasmonic NPs whose resonant wavelength matches a
photonic crystal surface, NP-PRAM demonstrates high contrast “digital resolution” precision sensing of exosomal
miRNAs. We plan to develop assays for simultaneous detection of 5 miRNA sequences extracted from a single
droplet of blood with a rapid assay protocol that does not require fluorescent emitters or enzymatic amplification.
We utilize simulation-guided miRNA probe design for ultraspecific hybridization. We will apply NP-PRAM in the
context of a panel of clinically validated miRNA biomarkers for advanced prostate cancer.
 Our approach offers important advantages compared to existing methods for detection of circulating nucleic
acid biomarkers: It requires only a ~50 µl droplet of test sample unlike 10-20 ml of blood for RT-PCR based
detection methods. NP-PRAM detection produces highly quantified results because nanoparticle tags are not
subject to the effects of quenching or background fluorescence that are common to fluorescent dyes. The assay
is isothermal, conducted at room temperature, and highly selective, while it does not require enzyme
amplification or w...

## Key facts

- **NIH application ID:** 9997542
- **Project number:** 1R01EB029805-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brian T. Cunningham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $556,370
- **Award type:** 1
- **Project period:** 2020-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997542

## Citation

> US National Institutes of Health, RePORTER application 9997542, Exosome separation and digital resolution detection of blood-based nucleic acid biomarkers for noninvasive therapeutic diagnostics in cancer (1R01EB029805-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997542. Licensed CC0.

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