William Chappell

Newman Cheng, Gordon Broadbent, Jason Dong et al.

We present Cognitive Loop via In-Situ Optimization (CLIO), an agent that couples a continuously-updated belief-state graph with a recursive plan-then-act loop. The result is a reasoning agent that can contribute something qualitatively different, which we term \emph{calibrated deference}: the capacity to recognize when its own tools or assumptions are failing, to adapt its strategy in response, and to generate mechanistic hypotheses that guide experimental revision. We tested CLIO in a closed-loop human-AI campaign to design an aqueous organic redox flow battery (AORFB) negolyte, with CLIO leading proposal and interpretation in close partnership with chemists who synthesized, characterized, and weighed in on design choices. Across 17 candidates over three rounds, CLIO converged on a top phosphonate candidate; characterization confirmed a 130~mV improvement in redox potential over the literature baseline. Characterization then revealed unexpectedly poor electrochemical reversibility -- a regression no property predictor had flagged. CLIO generated competing mechanistic hypotheses, prioritized discriminating diagnostics, traced the failure to phosphonate-potassium ion pairing, and prescribed a sulfonate replacement. The resulting compound showed substantially improved electrochemical reversibility and maintained a 90~mV improvement in redox potential, closing the design-make-test-redesign loop.

Newman Cheng, Gordon Broadbent, William Chappell

The capacity for artificial intelligence (AI) to formulate, evolve, and test altered thought patterns under dynamic conditions indicates advanced cognition that is crucial for scientific discovery. The existing AI development landscape falls into two categories: 1) frameworks over non-reasoning models that natively incorporate opinions on how humans think, and 2) reasoning models that abstract precise control of the reasoning intuition away from end users. While powerful, for scientists to maximize utility of AI in scientific discovery, they not only require accuracy and transparency in reasoning, but also steerability. Hence, we introduce an alternative approach that enables deep and precise control over the reasoning process called: a cognitive loop via in-situ optimization (CLIO). CLIO enables large language models (LLMs) to self-formulate ways of approaching a problem, adapt behavior when self-confidence is low, and ultimately provide scientists with a final belief or answer. Through CLIO's open design, scientists can observe uncertainty levels, understand how final belief states are formulated using graph structures, and interject corrections. Without any further post-training, OpenAI's GPT-4.1 with CLIO yields an accuracy of 22.37\% in text-based biology and medicine questions on Humanity's Last Exam (HLE). This yields a 13.82\% net or 161.64\% relative increase when compared to the base GPT-4.1 model and surpasses OpenAI's o3 performance in high and low reasoning effort modes. We further discovered that oscillations within internal uncertainty measures are key in determining the accuracy of CLIO's results, revealing how its open design and internal mechanisms can provide insight and control into scientific decision-making processes.