# PRISM: Protocol Refinement through Intelligent Simulation Modeling

arXiv: https://arxiv.org/abs/2601.05356 · HTML: https://mlsanity.com/paper/2601.05356/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 2 of its 23 references that are in the map.
- First posted on arXiv 8 Jan 2026.

## Builds on (most cited first, 2 of 2)

- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [ORGANA: A Robotic Assistant for Automated Chemistry Experimentation and Characterization](https://mlsanity.com/paper/2401.06949/) (2024)

## Abstract (arXiv)

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.