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PRISM: protocol refinement through intelligent simulation modeling

delete2026-05-01
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PRE
AI
H
Hsu, Brian
S
Setty, Priyanka V.
R
Rory Butler
R
Ryan Lewis
C
C. R. Stone
W
Weinberg, Rebecca
T
Thomas Brettin
R
Rick Stevens
I
Ian Foster
A
Arvind Ramanathan *
DOI:10.1039/d6dd00004edelete
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Abstract

Abstract

En 中文
Automating experimental protocol design and execution remains as a fundamental bottleneck in realizing self-driving laboratories. We introduce PRISM (Protocol Refinement through Intelligent Simulation Modeling), a framework that automates the design, validation, and execution of experimental protocols on a laboratory platform composed of off-the-shelf robotic instruments. PRISM uses a set of language-model-based agents that work together to generate and refine experimental steps. The process begins with automatically gathering relevant procedures from web-based sources describing experimental workflows. These are converted into structured experimental steps (e.g., liquid handling steps, deck layout and other related operations) through a planning, critique, and validation loop. The finalized steps are translated into the Argonne MADSci protocol format, which provides a unified interface for coordinating multiple robotic instruments (Opentrons OT-2 liquid handler, PF400 arm, Azenta plate sealer and peeler) without requiring human intervention between steps. To evaluate protocol-generation performance, we benchmarked both single reasoning models and multi-agent workflow across constrained and open-ended prompting paradigms. The resulting protocols were validated in a digital-twin environment built in NVIDIA Omniverse to detect physical or sequencing errors before execution. Using Luna qPCR amplification and Cell Painting as case studies, we demonstrate PRISM as a practical end-to-end workflow that bridges language-based protocol generation, simulation-based validation, and automated robotic execution.

Journal

Digital Discovery cover
Digital Discovery
IF:
5.6
Papers:
997
Citations:
1.7K

Organization

United States Department of Energy cover
United States Department of Energy
Scholars:
706
Papers: 230
Citations: 1.9K
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