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Closed-Loop Optogenetic Control in a Microplate Reader

delete2026-05-25
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H
Hari R. Namboothiri
K
Krishna Pochana
B
Bhavya Jaiswal
A
Azita Emami
C
Chelsea Y. Hu *
DOI:10.1021/acssynbio.6c00003delete
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Abstract

Abstract

En 中文
Optogenetics integrates living cells and electronics into powerful cell–silicon systems, but prototyping their dynamics remains challenging. Current tools either require robotic liquid transfers into flow cytometers or rely on custom sensors with a narrow dynamic range that limits controller performance. Additionally, current successful optogenetic feedback controllers only operate in chemostats or microfluidic devices that enforce constant growth, because models for growth-aware controller design in batch culture are lacking. Here, we present LEMOS, a low-cost LED-embedded microplate that runs inside a commercial microplate reader. Coupled with a growth-aware multiscale model of gene expression for controller tuning, this platform enables rapid design-build-test-learn cycles for cell-silicon systems. We demonstrate closed-loop set point tracking of gene expression in batch cultures within a standard microplate reader and show how growth dynamics complicate controller selection and tuning. Together, this platform reduces setup overhead and speeds up iteration, enabling accurate real-time optogenetic feedback control.
Keywords:
Fluorescence
Genetics
Light
Optogenetics
LEMOS
optogenetic feedback control
growth-aware gene expression dynamics
cybergenetics
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Journal

ACS Synthetic Biology cover
ACS Synthetic Biology
IF:
3.9
Papers:
3.9K
Citations:
1.2W

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T
texas a&m university
Scholars:
2.8K
Papers: 1.1K
Citations: 0
C
california institute of technology
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Papers: 1.1K
Citations: 0