# A Closed Loop Control System with Live Cells in the Loop

> **NIH NIH R21** · UNIVERSITY OF NEW MEXICO · 2021 · $217,492

## Abstract

A CLOSED LOOP CONTROL SYSTEM WITH LIVE CELLS IN THE LOOP
 This work proposes to develop and apply, for the first time, control theory-derived strategies to regulate autophagy in live
cells using an innovative experimental testbed with sensing and actuating capabilities. Combinations of pharmacological
interventions are used extensively for the treatment of many diseases. Therefore, there is significant potential for control theory-
based treatments to enhance the well-being of patients through careful tuning of dosage delivery of multiple pharmacological
reagents (PRs). Intracellular measurements of the formation of autophagy vesicles (AVs) in response to the application
of various PRs will be conducted using traditional fluorescence microscopy and an Amnis ImageStream Mark II Imaging
Flow Cytometer, available at the University of New Mexico (UNM) Autophagy, Inflammation, and Metabolism in Disease
Center of Biomedical Research Excellence (AIM Center), the only autophagy-focused CoBRE in the nation and in which
PI Sorrentino is an Associate Member. This state-of-the-art instrument uses flow cytometry and multispectral imaging to
detect intracellular AVs, providing an accurate count of total AVs (the output) within individual cells. A perfusive fluidic
delivery system to deliver drugs (the inputs) in time and in a controlled manner will be developed as part of the proposed
effort. This experimental testbed will provide a proof-of-concept realization of closed-loop control of autophagy in live-cell
experiments. In addition, an integrated mathematical model will be developed to describe the regulation of autophagy in
live cells by considering the effects of several PRs on the formation of AVs. Our control decisions will be explicated at two
levels: first, the choice of PRs to use in a combination study out of a set of available PRs; and second, the dosage function
for each PR in the combination, i.e., the rate at which the PR is supplied as a function of time, with time being a continuous
function. An innovative multi-scenario optimal controller will also be developed and tested to optimize the control actions in
the presence of limited experimental information and uncertainty about the state of the system.
 The UNM AIM Center hosts a team of specialists who conduct groundbreaking research into the role of autophagy in
inflammatory diseases and infection, and who provide mentoring opportunities for junior faculty. As an Associate Member
of the AIM Center, PI Sorrentino is in a unique position within a specialized, local environment to meet with success. The
long-term impact of the proposed research will be significant, as it has considerable potential to advance scientific knowledge
at the nexus of engineering and life sciences, and lead to the development of optimized therapies that could positively affect
the well-being of millions of patients worldwide.
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## Key facts

- **NIH application ID:** 10133071
- **Project number:** 5R21EB028489-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO
- **Principal Investigator:** Francesco Sorrentino
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $217,492
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133071

## Citation

> US National Institutes of Health, RePORTER application 10133071, A Closed Loop Control System with Live Cells in the Loop (5R21EB028489-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133071. Licensed CC0.

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