# A Label-Free, Many-Parameter Benchtop Platform for Functionally-Preserved, Viable Cancer Stem Cell Isolation and Biomarker Discovery to Probe Urothelial Carcinoma of the Bladder

> **NIH NIH R43** · NODEXUS, INC. · 2020 · $55,000

## Abstract

Nodexus’ previously developed NX One system leverages node-pore sensing electrical detection (non-
marker-based) and fluorescence-based marker detection of cells in combination with low-shear microfluidic
valving for viable cell sorting and single-cell isolation. In this proposal, we highlight a new instrument that
integrates our demonstrated node-pore sensing (“NPS”) single-cell isolation with label-free multi-marker
screening for the quickly emerging cancer stem cell (CSC) space, efficient biomarker discovery and
functional studies for targeted therapy development would be transformative, but easy access to viable,
functionally-preserved live single-cells is not possible using any single commercial instrument. While
the platform will eventually be applicable across more cancer subtypes, our initial point of entry into this sector
focuses on urothelial carcinoma of the bladder (UCB). Urothelial carcinoma of the bladder is the most common
malignancy of the urinary tract, with >600,000 living with bladder cancer and ~79,030 new cases and 16,870
deaths per year in the United States. From extensive conversations with experts in the field, we have found
critical pain points related to UCB that the Nodexus platform can address.
 CSCs are a subpopulation within a heterogeneous mixture of cancer cells that have enhanced pro-
malignant properties, but the contribution of specific markers to stem cell-like traits and their clinical utility as
biomarkers have not been conclusively determined, making targeted therapy for these cells extremely
challenging. A better understanding of the molecular mechanisms underlying urothelial CSC regulation and
identification of key molecules associated with CSC generation and maintenance are pivotal for the
determination of universally accepted, clinically-accurate biomarkers for early cancer detection and monitoring
following transurethral resection of bladder tumor (TURBT) as well as the development of effective targeted
therapies.
 The complexity with studying CSCs is immensely increased due to the heterogeneity within tumors and
the variance in CSC-like traits and functional importance in different cancer subtypes. Conclusive confirmation
of marker-associated functionality will open the door for targeted therapy development. Further studies of
comprehensive panels of markers performed simultaneously will provide significant value for downstream
studies for conclusive biomarker identification and optimized therapies. Critically, the functional relevance of
such markers must be evaluated and understood; this requires being able to comprehensively screen for
numerous markers, isolate single-cell populations to unveil masked heterogeneity, and perform downstream
functional studies (e.g. growth, invasion, and resistance to chemotherapeutic agents) on these viable,
functionally-preserved isolated single-cells. While existing technologies, such as FACS, MACS, and CyTOF have
provided tremendous value within the broader space,...

## Key facts

- **NIH application ID:** 10086817
- **Project number:** 3R43CA243815-01S1
- **Recipient organization:** NODEXUS, INC.
- **Principal Investigator:** Karthik Ratna Balakrishnan
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2019-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086817

## Citation

> US National Institutes of Health, RePORTER application 10086817, A Label-Free, Many-Parameter Benchtop Platform for Functionally-Preserved, Viable Cancer Stem Cell Isolation and Biomarker Discovery to Probe Urothelial Carcinoma of the Bladder (3R43CA243815-01S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10086817. Licensed CC0.

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