# High throughput antibody discovery against cell membrane bound target proteins using innovative MOD technology for direct screening in single-cell assays

> **NIH NIH R43** · SCRIBE BIOSCIENCES, INC. · 2023 · $300,000

## Abstract

ABSTRACT
Scribe Biosciences are leading experts in the field of droplet microfluidics and have developed a best-in-class
droplet manipulation platform, Microenvironment on Demand (MOD), that can currently assemble >100k
paired-cell assays in <3 hours, with proven proof of concept. Using this innovative technology, this SBIR Phase
1 project proposes the development and quantification of assay methods to be used for single-cell functional
screening workflows to enable large scale screening of therapeutic antibody (Ab) candidates. The development
of such a workflow to reliably, consistently, and repeatably identify large and diverse pools of B cell hits would
offer a significant advantage over the classical but inefficient hybridoma method. Porting direct B-cell assays to
microfluidics is a natural fit because short lived B-cells can rapidly generate significant secreted Ab
concentrations when incubated in appropriately small volumes; current attempts are limited by cost and
scalability, and none offer high throughput (HT) assays against target cells, sensitive assays, or integrated HT
sequencing. MOD represents an evolutionary advancement in the capability to build droplet-based cell assays
with precision and scale, effectively integrating assay construction, readouts, hit selection, and sample prep into
a single workflow and instrument. MOD co-encapsulates Ab-secreting and target cells in the same microfluidic
droplet, which enables building an assay based on the target cell, since it will carry along the Ab-secreting cell
and therefore the RNA that is available to identify the Ab in a subsequent sequencing step. MOD utilizes flow
cytometry-style detection and sorting, so it is readily scalable for HT. The approach for this project has been
informed by previous work developing assays on the MOD platform. In the first aim, two assays will be developed
to detect Ab binding against membrane protein targets. The first will adopt an existing bead-based no wash
assay scheme for use with high copy number targets, and the second will develop a more sensitive assay for
low copy number targets with a wash step, and will explore the appropriate method for creating a durable physical
linkage between the cells that will last through FACS sorting or re-encapsulation. The second aim will test and
quantify the system with B-cells from immunized mice for a real-world demonstration of Ab discovery. B-cells will
be sourced from standard 4-week immunization protocols on groups of 3 mice using SARS-CoV-2 as the antigen,
and will be used to explore the parameters of primary B-cell culture in droplets and other factors associated with
porting B-cell biology on to the MOD platform. A small batch (50-100k) of B-cell/target cell assays will be tested,
and assuming that the HT of the platform will correlate with a high number of hits (~1000 positive assays), a
small number (~10) of Ab candidates will be bioinformatically selected for subsequent re-cloning and hit
validation...

## Key facts

- **NIH application ID:** 10698891
- **Project number:** 1R43AI177129-01
- **Recipient organization:** SCRIBE BIOSCIENCES, INC.
- **Principal Investigator:** Russell H Cole
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2023-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698891

## Citation

> US National Institutes of Health, RePORTER application 10698891, High throughput antibody discovery against cell membrane bound target proteins using innovative MOD technology for direct screening in single-cell assays (1R43AI177129-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10698891. Licensed CC0.

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