# Molecular Digital CytoImaging for Leukemia Drug Screening

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $587,933

## Abstract

Current cytometry technologies query cell phenotype and protein expression but do not reliably measure
key, clinically-relevant proteins that are challenging to detect in single cells due to their low basal levels
and/or diminished levels following drug treatment (e.g. phosphoproteins, immune regulatory proteins). As
a result, many drug targets are not evaluated and the absence of detection cannot be reliably interpreted
as a negative result. To overcome major bottlenecks in sensitive protein detection, OHSU and Becton
Dickinson (BD) will commercially translate an imaging technology that will enable investigators to perform
drug screening with unprecedented molecular-level sensitivity in primary patient samples. We have built a
platform, the DigiCount, that implements a new strategy of counting discrete immunolabeled proteins in
the presence of diffuse background noise (e.g. cell autofluorescence) in single cells (Jacob et al, Nat Sci
Reports 2016; OHSU: 1 patent filed, 2 pending). Proprietary digitized molecular-localization algorithms
discriminate discrete protein complexes tagged with ultrabright antibody-fluorophore probes, offering up to
1-2 log times increased signal to noise over conventional flow cytometry/fluorescence microscopy. We will
scale up the DigiCount throughput for efficient clinical screening. We will also generate additional probe
panels that include markers of clinically-relevant/low abundance proteins (stem cell, immune regulatory,
phosphoproteins) to further increase target screening information. Probe panels leverage a new class of
conductive polymer dyes with efficient light harvesting amplification chemistry and ultrabright emission
(Nobel Prize, 2000). The probes are selected from BD's compound library, and specifically optimized for
digitized molecular detection. In pilot screening of acute myeloid leukemia 1 patients enrolled in the Beat
AML study, an ongoing 900 patient study to identify improved AML targeted therapies (OHSU Knight
Cancer Institute), we have identified synergistic small molecule/immune checkpoint inhibitor combinations
that produce AML cell kill and induce immune cell proliferation more effectively than single molecule
agents. We will apply the DigiCount to screen hundreds of combinations per patient to determine if there
are main classes of small-molecule/immune checkpoint inhibitor combinations that are more effective than
single agents. We will also profile the effects of promising combinations to characterize their effect on
immune and myeloid cell targets. The research team consists of the innovator of single cell imaging
technologies (PI: Vu, OHSU), a lead scientist with expertise in tandem polymer fluorophores and
novel/HCA assay development from the commercial sector (PI: Martin, Becton Dickinson), and clinician-
scientists leading efforts to identify AML targeted therapeutics for clinical deployment (co-PIs: Tyner, Lind,
OHSU). Letters of support from key opinion leaders attest to the innov...

## Key facts

- **NIH application ID:** 9960447
- **Project number:** 5R01CA222095-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jody Martin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $587,933
- **Award type:** 5
- **Project period:** 2018-07-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960447

## Citation

> US National Institutes of Health, RePORTER application 9960447, Molecular Digital CytoImaging for Leukemia Drug Screening (5R01CA222095-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960447. Licensed CC0.

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