# Determining treatment sensitivity in B cell lymphoma by novel microfluidics-based NK cell immunogenicity platform

> **NIH NIH R33** · NORTHEASTERN UNIVERSITY · 2020 · $379,335

## Abstract

Abstract
 B cell non-Hodgkin lymphomas (bNHL) are the most common lymphoma subtype representing >85% of
all NHLs. bNHL are typically treated the anti-CD20 antibody (e.g., rituximab) alone or in combination with
chemotherapy. There are currently, however, no biological methods or markers to predict the sensitivity or
resistance to rituximab (or any other) antibody therapy. A key feature of antibody activity occurs through natural
killer (NK) cell-mediated killing of antibody-coated target tumor cells, however, antitumor activity and subsequent
resistance, is poorly understood. In this application, we propose to develop and validate a high throughput droplet
based microfluidic platform to investigate the key features of NK cells associated with rapid, slow or inactive
tumor killing kinetics in NHL. We will first adapt a novel approach and integrate the biocompatible acoustofluidic
droplet sorter during the droplet microarray formation to determine the phenotypes of immune-target cell
interaction in microfluidic droplets. We will validate a droplet-based microfluidic device to interrogate single-cell
dynamic responses and cell-cell interactions within intact droplets. Next, we will demonstrate a high-purity
(>95%), high-throughput (>10,000 events/s), four-channel acoustofluidic droplet sorter to integrate with droplet
analysis array. The downstream 4-channel sorting will allow, after establishing the kinetic profiles of interactions,
to identify and sort droplets containing active lymphocytes into a distinctive pool; separate basal lymphocytes
into another pool based on fluorescence. A unique function of selecting sorting criteria based on imaging analysis
can be provided by the combination of droplet imaging array and acoustofluidic droplet sorters, which is
unachievable for conventional fluorescence activated droplet sorters (FADS) since imaging tracking is inherently
tricky in high-speed flow. Thus, our approach serves as a “bottom-up” method of classification, by first identifying
distinct functional categories and then probing the content of the individual cell category to determine the key
factors for the molecular classification of heterogeneous immune functions of NK cells related to target cell kill.
In addition, we will identify NK cell heterogeneity and bio-functional characteristics to discover novel drug
combinations for NK cell dependent immunotherapy via an integrated acoustofluidic droplet sorting platform. We
will demonstrate that the accuracy of phenotype identification of our device and its suitability for clinical
applications by monitoring and classifying NK/NHL single cell interactions in the presence of monoclonal
antibodies and performing biochemical secretome assay from ‘hyperactive’, ‘basal’ and non-responsive pools.
By combing these findings with drug screening and identification of phenotype altering drugs, we will
demonstrate the applicability of this technology for personalized medicine and rational clinical
immunothera...

## Key facts

- **NIH application ID:** 9919540
- **Project number:** 5R33CA223908-03
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Andrew M Evens
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,335
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919540

## Citation

> US National Institutes of Health, RePORTER application 9919540, Determining treatment sensitivity in B cell lymphoma by novel microfluidics-based NK cell immunogenicity platform (5R33CA223908-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9919540. Licensed CC0.

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