Source-linked AI summary

La Agente \'Optima: Towards Agentic Self-Driving Laboratories

Marcel Müller, Jiaru Bai, Willi Gottstein, Abhijoy Mandal, Mohammad Nazeri, Elia Savino, Yanlin Fang, Sujoy Das, Sergio Pablo García Carrillo, Yeonghun Kang, Juan B. Pérez-Sánchez, Simone Pilon, Martin Fitzner, Timothy Noël, Frank Gu, Varinia Bernales, Alán Aspuru-Guzik

arXiv:2609.04564v1cs.AIcs.MAphysics.chem-ph

TL;DR

Scientists often need programming and BO expertise to deploy and maintain closed-loop campaigns. Óptima separates agent reasoning from campaign execution and persistent optimization state, supporting campaign construction and supervision across computational and experimental systems. Across benchmarks and case studies, it can shift between BO search and direct agent proposals; its RoboChem-Flex campaign was 13% cheaper than a human-directed campaign.

  • Problem

    Deploying Bayesian optimization still typically requires programming and BO expertise to connect evaluators, maintain campaigns, and interpret their trajectories.

    Source: §1 · p. 2
  • Method

    Óptima autonomously constructs and manages BO campaigns across computational and experimental systems while separating agent reasoning from programmatic execution and persistent optimizer state.

    Source: §1 · p. 3
  • Results

    Across benchmarks and case studies, Óptima shifted between BO search and direct agent proposals; its RoboChem-Flex campaign was 13% cheaper than a human-directed campaign.

    Source: §4 · p. 13
  • Takeaways & Limitations

    Researchers can revise a campaign's scientific question through natural language, with Óptima translating the decision into campaign changes while preserving its state.

    Source: §4 · p. 13

    Campaign diagnosis and advice depend on available evidence: numerical observations alone can incompletely represent failures, making access to sensor data and platform state important.

    Source: §4 · p. 13

Abstract

from arXiv · show

Self-driving laboratories (SDLs) combine automated experimentation with adaptive decision-making to accelerate scientific discovery. Their operation nevertheless often depends on human specialists who translate scientific objectives into executable closed-loop campaigns. Specialists adjust them as data and operating conditions change. Here, we present La Agente \'Optima, an agentic framework that constructs and supervises Bayesian optimization campaigns across computational and experimental systems while maintaining a persistent optimization state. By separating large language model (LLM) reasoning from executed campaigns, \'Optima runs repetitive optimization loops consistently, returns control to the agent only when progress requires interpretation or campaign revision, and keeps every decision auditable. We evaluate \'Optima across ablation studies, five digital discovery tasks, and two physical platforms. Throughout, \'Optima maintained executable campaigns as both the scientific problem and execution environment evolved. In a closed-loop contact angle optimization campaign, \'Optima identified and corrected a mid-run measurement failure, bringing the contact angle from 71.4 to 67.8 degrees, just above the 64-66 degree range. From this result, \'Optima correctly inferred that the target was likely unattainable with the available reagents and recommended changing the formulation. In a five-day multi-objective flow-chemistry campaign, \'Optima increased the yield from 30% to 59% over 23 experiments. Despite substantial inference costs, it cost less and used substantially less starting material than a human-directed campaign, while selecting a more mass-efficient operating point. These results show that LLM-based agents can make rigorous, long-running optimization campaigns accessible to domain scientists without specialist setup, expanding the scope of SDLs.

1 Introduction

Bayesian optimization and self-driving laboratories address costly, large scientific search spaces, but deploying and scaling such campaigns still requires specialist expertise. Óptima combines agent reasoning with dedicated optimization to manage campaigns across computational and experimental systems.

1 Introduction

  • BO guides sequential experiments in large, costly search spaces, but connecting, maintaining, and interpreting campaigns still typically requires programming and optimization expertise.SDLs close the loop by using each round of testing to inform the next experiment.Source: §1 · p. 2
  • As campaign scale grows, human intervention can become a bottleneck; accessible interfaces and reliable semi-autonomous operation are identified as desirable.A cited catalysis campaign required 34.7 person-hours of human reasoning across 160 experiments, compared with about 1 hour of agent reasoning at twice the experimental throughput.Source: §1 · p. 2
  • Prior agent-based wet-lab campaigns sustained multiple rounds but remained tied to execution environments tailored to particular tasks and platforms.Examples include Coscientist and a GPT-5/cloud-laboratory protein-synthesis campaign.Source: §1 · p. 2
  • LLM-driven proposals can use pretrained chemical knowledge, whereas dedicated BO offers a complementary data-driven strategy when prior knowledge is sparse or unreliable.A reported 25-dimensional catalysis campaign found narrow LLM search and silent reasoning errors; a domain-expert team explored more diverse formulations within the same experiment budget.Source: §1 · pp. 2–3
  • Existing LLM/BO hybrids remain private to particular agents or workflows and are evaluated on benchmarks or within single domains, motivating a shared persistent optimizer across platforms.Óptima presents that architecture for computational and experimental campaigns while keeping decisions auditable.Source: §1 · p. 3

2 Implementation

Óptima separates campaign authoring, optimization state, execution, and supervision across computational and experimental systems. Its implementation connects a persistent BO service and platform-specific interfaces to campaigns whose artifacts remain inspectable.

2.1 Agentic framework

  • The agent delegates campaign authoring to a BO specialist, which writes Python programs and instructions; Óptima monitors execution and intervenes when interpretation or revision is needed.The specialist retains reusable implementation lessons, and campaign artifacts remain inspectable in a shared workspace.Source: §2.1 · pp. 3–4

2.2 BO-MCP

  • BO-MCP exposes optimizer operations through MCP and REST, maintains per-campaign action and provenance records, and supports replaceable BayBE and BoTorch backends.It records suggestion provenance, predictions, uncertainty, and backend-specific measures such as kernel lengthscales or SHAP-based importance.Source: §2.2 · pp. 4–5

2.3 PySCF execution graph

  • For PySCF tasks, generated campaign code evaluates candidates under common settings, validates calculations through typed workflow nodes, and submits structured results to BO-MCP.Independent candidates can run concurrently in isolated GPU processes.Source: §2.3 · p. 5

2.4 Agent-to-agent integration with El Agente Estructural

  • El Agente Estructural handles molecular-structure generation and editing over HTTP, while shared workspace files keep atomic coordinates out of the LLM context.The campaign script can call the same service directly during long optimization loops.Source: §2.4 · p. 5

2.5 RAISE platform access

  • RAISE returns validated static contact-angle measurements through an MQTT bridge, with experiments serialized because its shared request and response channels lack identifiers.The platform measures about one contact angle per minute and reduced measurement variability by 20–62%, depending on substrate, in its benchmark against conventional goniometry.Source: §2.5 · p. 5

2.6 RoboChem-Flex platform access

  • RoboChem-Flex integration checks proposed conditions against live platform capabilities, while RoBridge enforces campaign, robot-state, and vial-layout safeguards.Optimization state remains in BO-MCP, while platform and safety state remain in RoBridge.Source: §2.6 · p. 6

3 Results

Óptima was evaluated in computational discovery and live experimental campaigns, alongside controlled ablations. The results support combining established Bayesian optimization with programmatic execution, while showing that optimization quality and operational robustness vary by task.

3.1.1 Combinatorial molecular discovery for organic solid-state lasers

  • After expansion to 2,592 candidates, Óptima completed 38 successful observations, identified recurring molecular motifs, and recovered from a Stage 1 configuration mismatch.The expanded space covered about 0.6% of theoretical combinations; the agent diagnosed and patched its evaluator, validated the fix, and resumed without human intervention.Source: §3.1.1 · p. 7, Figure 2 · p. 7

3.1.2 Finite-space discovery across chemistry and materials

  • Across four finite-space tasks, Óptima diagnosed conflicting ligand objectives, evaluator limits, geometry failures, and incompatible MOF representations instead of treating each as an optimization problem alone.It stopped ligand search as returns diminished, switched to a cheaper method after runtime estimates proved optimistic, traced Co-catalyst failures to unconverged geometries, and rebuilt MOF variables as compatible triples while retaining prior observations.Source: §3.1.2 · pp. 8–9

3.2 Closed-loop formulation optimization with RAISE

  • In RAISE, the best contact angle improved from 71.4° at warm start to 67.8° in the final one-shot, but remained outside the 65 ± 1° target window.Óptima identified failed measurements as missing data rather than unfavorable outcomes, resumed with valid observations without repeating physical experiments, and recommended changing the formulation after the boundary result.Source: §3.2 · pp. 9–10, Figure 3 · p. 9

3.3 Multi-objective flow photochemistry with RoboChem-Flex

  • Óptima increased photocatalytic trifluoromethylation yield from 30.0% among informed seeds to 58.8% on RoboChem-Flex.The live campaign replaced the platform’s dedicated optimization engine as the experimental-design decision-maker and transferred history between objectives.Source: §3.3 · p. 10

3.3.1 Campaign design under platform constraints

  • Óptima mapped the reactor’s nominal 0–100% light-intensity request to the mounted array’s realizable discrete settings, preserving hardware constraints.It also translated named search-space parameters into platform requests and exposed a hypothetical request for operator inspection before hardware execution.Source: §3.3.1 · pp. 10–11

3.3.2 Multi-objective optimization and objective revision

  • After switching to yield-only optimization, yield rose from 30.0% among informed seeds to 58.8%, adding a high-yield endpoint as green score fell from 82.5 to 74.4.The campaign transferred valid observations between objectives, and BO converged on chemistry related to the published RoboChem-Flex optimum.Source: §3.3.2 · pp. 11–12, Figure 4 · p. 11

3.3.3 Long-horizon execution and analytical diagnosis

  • During unattended hourly runs, Óptima inspected raw 19F spectra to distinguish genuine zero yield from analytical failure, while failed runs were retried or paused.The campaign supervisor flagged zero-yield and no-peak analyses and was configured to halt after five consecutive such outcomes.Source: §3.3.3 · p. 12

3.3.4 Resource use relative to human-directed optimization

  • The agent campaign used 23 experiments versus 50 for the human-directed campaign, cost 13% less, and reached 58.8% yield versus 63.9% at matched consumable budget.Both agent-identified optima were more mass-efficient; across the complete campaigns, the agent had two zero-yield experiments versus 27 for the human-directed campaign.Source: §3.3.4 · p. 12

4 Discussion

Óptima can shift between BO search and agent-proposed experiments, and can revise a campaign as the scientific question changes while preserving its state. The discussion also identifies evidence access, long-horizon context management, and operating costs as important constraints on this adaptability.

4 Discussion

  • The framework can move between classical BO search and agent-selected experiments when accumulated evidence or remaining budget calls for scientific judgment.The architecture comparison demonstrated programmatic BO for routine search, while the RAISE experiment showed direct experiment proposals by the agent.Source: §4 · p. 13
  • Óptima translates a revised scientific question into campaign changes while preserving state, avoiding manual stopping, state preservation, and campaign reconstruction.Examples include replacing a search-space representation in the MOF study and changing the objective in RoboChem-Flex while retaining experimental history.Source: §4 · p. 13
  • Numerical results alone can leave events ambiguous; sensor data can support diagnosis, while expanded sensing and control should remain bounded by safety interlocks and human authorization.The discussion cites an inherited evaluator bias, a missing value after changed imaging conditions, and a zero-yield result interpretable only after raw-spectrum inspection.Source: §4 · p. 13
  • Persistent workspaces, executable programs, and event-driven monitoring let Óptima resume changed campaigns and attend when a decision or notification is needed.Incremental process output is filtered into compact progress events, preserving visibility during long-running experiments.Source: §4 · p. 13
  • In RoboChem-Flex, the complete agent campaign was 13% cheaper despite inference costing more than the chemistry, and used 46% of experiments and 39% of starting material while finding more mass-efficient conditions at lower final yield.Further inference-cost reductions would strengthen the cost advantage; reducing equipment occupancy requires accounting for experiment duration as well as expected information.Source: §4 · p. 13
  • Long-running orchestration may require structured campaign context separating persistent objectives, constraints, and evidence from transient execution details.The discussion cautions that retaining an ever-growing history or compressing it into an undifferentiated summary may be insufficient when decisions depend on earlier observations.Source: §4 · p. 14
  • The broader vision is natural-language campaign specification followed by adaptive design selection, execution orchestration, and traceable decisions across computational and laboratory systems.For concurrent campaigns, agents could query one another for structured information about objectives, observations, decisions, and resource requirements.Source: §4 · p. 14

Supporting Information

The Supporting Information expands on BO-MCP implementation, covering request flow, backend selection, campaign tracking, auditability, and molecular design-space representation.

Supporting Information

  • The Supporting Information expands the main-text BO-MCP implementation with details on request flow, backend selection, campaign tracking, auditability, and molecular design spaces.These topics are covered in Sections A.1 through A.5.Source: A BO-MCP: system architecture and… · p. 22

A.1 Request flow and architecture

BO-MCP routes clients through shared campaign operations while separating optimization backends, persistent storage, lifecycle control, diagnostics, and molecular representations.

A.1 Request flow and architecture

  • MCP and REST adapters invoke shared, protocol-neutral campaign operations, which coordinate a pluggable optimization backend and persistent storage.The storage layer supports PostgreSQL for shared deployments and SQLite for isolated single-user use.Source: §A.1 · p. 22, Figure 6 · p. 22

A.2 Backend abstraction and algorithm selection

  • BayBE is the default backend, while BoTorch is retained for legacy use; backend capabilities determine which optimization features are available or automatically selected.Trust-region search is automatically dispatched for single-objective campaigns with at least 20 parameters; implemented SAASBO, multi-fidelity, and RGPE modules are not yet automatically dispatched.Source: §A.2 · p. 23, Table 3 · p. 24

A.3 Campaign lifecycle and concurrency

  • Campaigns use versioned lifecycle states, and version checks reject racing writes rather than silently overwriting newer state.Pause, resume, and terminate retries can succeed as no-ops when the campaign is already at the intended state; reopen has no such fallback.Source: §A.3 · p. 24, Table 5 · p. 25

A.4 Provenance, diagnostics, and explainability

  • BO-MCP records tool-call audit events and provides on-request diagnostics, while recording suggestion-generation methods and model provenance where available.Audit writes are best-effort by default; diagnostics include Pareto-front and hypervolume information for multi-objective campaigns, with some diagnostics depending on the backend.Source: §A.4 · pp. 25–26

A.5 Molecular and other categorical representations

  • BayBE can encode molecular categories using SMILES-derived or user-supplied numerical descriptors rather than treating molecular labels as unrelated categories.Large combinatorial candidate spaces may be deterministically subsampled above a configurable budget, then combined with valid observed and actionable pending configurations.Source: §A.5 · p. 26

B Framework comparison

Across the architecture benchmarks, Specialist-script performed strongly on Ackley 6D and reached maximum Shields arylation yield in all three runs, while specialist-model outcomes varied by task. The comparisons use targeted end-to-end ablations and distinguish optimization quality from workflow validity.

B Framework comparison

  • The architecture comparison tests targeted end-to-end variants rather than a full factorial decomposition, using Specialist-script, Main-script, Tool-loop, and Local-BO.The proposed Specialist-script separates specialist campaign authoring from main-agent execution and monitoring.Source: B Framework comparison · p. 27

B.1 Framework-comparison evaluation details

  • The evaluation used Ackley 6D and a 1,728-reaction Shields arylation benchmark, with three runs per architecture–benchmark combination and 60 attempted evaluations per run.Final quality uses native benchmark units, while MBSF@60 averages normalized best-so-far quality across attempts.Source: B Framework comparison · p. 27

B Framework comparison

  • Specialist-script achieved the strongest Ackley 6D performance and reached maximum Shields arylation yield in all three runs, although Main-script had the highest mean Shields arylation MBSF@60.All four architectures passed the full protocol; Tool-loop requires explicit tool-mediated result submission and evaluation execution at every iteration.Source: B Framework comparison · pp. 27, 29, Figure 7 · p. 28
  • Specialist-model performance was task dependent, and optimization quality and operational robustness were distinct; GPT-5.4’s strong results may partly reflect development bias.The authors characterize the results as behavioural and architectural trends, not a model leaderboard, given the small and unequal numbers of comparable trajectories.Source: Figure 8 · p. 29, B Framework comparison · p. 30

B.1.1 Validity and aggregation criteria

  • Equal-budget quality aggregates included only globally budget-valid, scientifically comparable runs, while reliability analysis retained all requested outcomes.Full-protocol validity additionally required architecture and artifact checks to pass.Source: §B.1.1 · p. 30

B.1.2 Detailed architecture comparison

The ablations show Specialist-script’s advantage was clearest on Ackley 6D. The phosphine campaign also documents an agent-managed search configured around four jointly minimized objectives.

B.1.2 Detailed architecture comparison

  • On Ackley 6D, Specialist-script had the highest mean terminal quality and MBSF@60; on Shields arylation, it reached 100% yield in all three runs.Main-script produced 100%, 100%, and 99.81% on Shields arylation, yielding nearly identical mean terminal performance.Source: §B.1.2 · p. 31
  • Tool-loop had the lowest mean Ackley 6D performance, while Main-script outperformed the other two ablations but remained below Specialist-script.The comparisons concern complete workflows with three repeats, not isolated causal estimates for individual components.Source: §B.1.2 · p. 31
  • Specialist-script’s lead on Ackley 6D emerged after attempt 10 and persisted through attempt 60, consistent with its later-horizon advantage.Main-script was slightly ahead after 10 attempts; Specialist-script led after 20 and remained ahead through 60.Source: §B.1.2 · p. 31

C.1 Phosphine ligand electronic tuning

  • Óptima’s phosphine campaign used a finite, enumerated ligand space and minimized four objectives: HOMO error, gap error, excess volume, and heavy-atom count.The campaign was a digital ligand-level proxy for catalyst tuning, with a categorical candidate_id search over pre-validated ligands.Source: §C.1 · p. 32, §C.1.2 · p. 32

C.1.2 Campaign configuration

  • The agent chose eight warm-start ligands to bracket the electronic axis rather than provide a space-filling design.The selections covered an alkyl-to-aryl series, bulky-alkyl probes, and electron-rich and electron-poor aryl boundaries.Source: §C.1.2 · p. 32

C.1.3 Execution and outcome

The phosphine campaign expanded its Pareto front while hypervolume gains diminished, revealing trade-offs among ligand objectives. The section also records autonomous repair and a separate singlet–triplet gap campaign with an operator-reviewed evaluation protocol.

C.1.3 Execution and outcome

  • After the first invocation, the agent recommended five further batches using a stopping rule based on flattening hypervolume gains and new Pareto members; the operator instead requested 20 more evaluations.All 48 evaluations ultimately succeeded, with no failed candidates or duplicate suggestions.Source: §C.1.3 · p. 33
  • No evaluated ligand met both electronic-target tolerances; BO instead found smaller ligands with similar electronic properties.P(iPr)(pCF3Ph)2 nearly matched P(pCF3Ph)3’s HOMO error while improving gap error and removing seven heavy atoms and 55 Å3 of volume; the steric term was non-zero for only one of 48 ligands.Source: §C.1.3 · pp. 33, 35
  • 0.791 to 1.038: normalized dominated hypervolume rose over 48 evaluations, while the Pareto front grew from 3 to 17 members.The second invocation added most of the late Pareto-front growth but only about 7% of hypervolume; Figure 9 plots both measures.Source: §C.1.3 · p. 33, Figure 9 · p. 34

C.1.4 Failure mode and autonomous repair

  • A silent progress monitor traced to a process-global stdout redirect; the agent added a lock and continued single-threaded.The campaign itself completed normally, and the specialist recorded the lesson for future campaign packages.Source: §C.1.4 · p. 35

C.1.5 Resource usage and provenance

  • 128 LLM calls cost $7.08, and the agent assembled campaign records, reports, logs, and a SHA-256 manifest into a reproducibility bundle.The 48 production DFT evaluations were run by the campaign script, not by the agent.Source: §C.1.5 · p. 35

C.2 Singlet–triplet gap search over the Pollice 2021 library

  • The separate Pollice-library campaign searched for the smallest TD-DFT singlet–triplet gap across 1512 molecules, using the published dataset to assess a digital proxy.Evaluations combined conformer search and excited-state calculation, unlike the phosphine campaign’s single ground-state job.Source: §C.2 · p. 36

C.2.1 Task definition and division of labour

  • For each selected molecule, the protocol generated low-energy conformers, kept the lowest-energy one, and reported ΔEST from a fixed TD-DFT calculation.The operator corrected the agent’s timing estimate from about 2.5 minutes to about 11 minutes, prompting a revised 6–15-hour estimate and a cheaper PBE0 fallback.Source: §C.2.1 · p. 36

C.2.2 Campaign configuration

  • The campaign used molecule_key as a categorical search variable and agent-built descriptors from SMILES, while rejecting failed evaluations rather than submitting them as observations.Descriptors included 12 RDKit scalars, 32 truncated-SVD fingerprint components, and an identity code.Source: §C.2.2 · p. 36

C.2.3 Execution and outcome

The section reports a singlet–triplet gap campaign and a cobalt bisphosphine campaign coordinated across separate services. It details the search outcomes, failure handling, resource use, and campaign configuration.

C.2.3 Execution and outcome

  • Among 44 attempts, 39 succeeded; the best methylsulfinyl cycl[3.3.3]azine reached ∆EST = 0.223 eV, with E(S1) = 1.398 eV and E(T1) = 1.175 eV.All 39 successful evaluations were distinct molecules.Source: §C.2.3 · pp. 36, 38
  • Only the 37th success improved on the initial 0.227 eV record, by 3.6 meV; BO-guided mean observed gap was 0.302 eV versus 0.429 eV initially.Nine of the ten best molecules were monosubstituted cycl[3.3.3]azines and the tenth was a triazine-fused heptazine analogue, recovered from a 1512-molecule table without a chemical prior.Source: §C.2.3 · p. 38
  • PBE0/def2-SVP gaps averaged +0.33 eV above references yet ranked them well (Spearman ρ = 0.79; Pearson r = 0.89), so absolute gaps remained unreliable.The smallest campaign gap was +0.223 eV, while aggregated reference values for the same top molecules were near −0.34 eV.Source: §C.2.3 · pp. 38–39

C.2.4 Failure modes and autonomous response

  • Failures comprised one >7200 s timeout kept as a deliberate budget and four CUDA infrastructure faults, which Óptima stopped, reproduced on water, and patched with CPU fallback.The agent flagged that the CPU-fallback patch was a host-environment fix outside the campaign package and would need reapplication or avoidance during reproduction.Source: §C.2.4 · p. 39

C.2.5 Resource usage and provenance

  • The 44 evaluations used 7.1 h of cumulative evaluator time; agent inference cost $13.01, and the operator received a reproduction bundle with campaign artifacts and environment metadata.The three invocations occupied 6 h 15 min of campaign time.Source: §C.2.5 · p. 39

C.3 Agent-to-agent cobalt catalyst tuning

  • In the cobalt campaign, Óptima coordinated a finite Co(II) complex search while separate services owned structure construction, optimizer state, and DFT evaluation.The campaign required metal complexes to be built from textual ligand descriptions before electronic-structure calculations.Source: §C.3 · p. 40

C.3.1 Task definition and division of labour

  • The operator fixed the search scope and geometry-only budget; Óptima authored the campaign, BO-MCP held optimizer state, and separate agents built structures and ran evaluations.No single component held the whole problem: Óptima did not manipulate coordinates, the structure agent did not see objectives or optimizer state, and BO-MCP did not see molecules.Source: §C.3.1 · p. 40

C.3.2 Campaign configuration

  • The search enumerated 144 duplicate-free ligand candidates and represented each with nine custom descriptors; a candidate counted successful only after completed geometry optimization without failure indicators.The descriptor vector encoded linker properties, substituent steric and electronic properties, symmetry, and identity.Source: §C.3.2 · pp. 40–41

C.3.3 Execution and outcome

The cobalt campaign improved feasible-only objectives despite evaluator failures, while the Xe/Kr campaign exposed a combinatorial search-space defect that Óptima diagnosed.

C.3.3 Execution and outcome

  • Six of 14 candidates were feasible; seven failures were unconverged geometry optimizations and one exceeded the workflow timeout.The SCF converged in all seven failed relaxations.Source: §C.3.3 · p. 42
  • Hypervolume rose from 0.572 to 1.000 after six feasible evaluations; best electronic activation improved from −0.083 to 0.192, with four candidates on the Pareto front.The figure plots feasible evaluations and the best feasible value so far.Source: §C.3.3 · p. 42, Figure 11 · p. 42

C.3.4 Resource usage and provenance

  • The 4 d 23 h session used 1.79 h of agent-run time and cost $53.29; PySCF consumed 4.87 h, with failed relaxations dominating campaign cost.El Agente Estructural handled 8% of input tokens but 27% of the spend.Source: §C.3.4 · p. 43

C.4 Xe/Kr separation over PORMAKE-assembled MOFs

  • The Xe/Kr showcase used a purely geometric evaluator and exposed a combinatorial search-space error that the agent diagnosed and replaced.Candidates were assembled with PORMAKE and scored with Zeo++; each evaluation took a few seconds.Source: §C.4 · p. 44

C.4.1 Task definition and division of labour

  • The operator set nine topologies, tools, objectives, and a 30-evaluation budget, while leaving batch size, iteration count, and initial design to the agent.The agent also selected building blocks, defined objective proxies, and wrote campaign code and reporting.Source: §C.4.1 · p. 44

C.4.2 Campaign configuration

  • The agent excluded rtl and tbo, ranked compatible nodes by local-structure RMSD, and defined a bounded selectivity score alongside Zeo++ pore volume.The selectivity score saturates for pore-limiting diameters of 3.6–7.0 Å and is damped above a largest-cavity diameter of 12 Å.Source: §C.4.2 · p. 44

C.4.3 The first campaign and its parameterization failure

  • The independent categorical encoding created 2,800 nominal triples but only 420 constructible ones; 15 of 30 evaluations were rejected as incompatible and submitted as zeros.Only one initial-design point was constructible, but the optimizer learned the constraint from penalized observations.Source: §C.4.3 · p. 44
  • All 15 successful first-campaign candidates were pcu; Óptima identified the 50% invalid rate and recommended a refined campaign restricted to validated triples.It offered unchanged continuation and local screening as alternatives; the operator selected the refinement.Source: §C.4.3 · p. 45

C.4.4 The refined campaign and outcome

The refined MOF campaign corrected the initial parameterization, completed 50 new evaluations without failures, and modestly improved desirability; the section also describes a closed-loop RAISE campaign.

C.4.4 The refined campaign and outcome

  • All 50 refined evaluations succeeded using 109 validated constructible triples, with 15 successful prior evaluations carried forward as historical seeds.The single candidate_id parameter decoded to topology, node, and edge; no suggestion was rejected.Source: §C.4.4 · p. 45
  • Scalarized desirability rose from 0.487 to 0.502, and the observed Pareto front grew from 7 to 12 members, with 7 contributed by the follow-up.The improvement curve plots 15 historical seed observations and 50 refined evaluations.Source: §C.4.4 · p. 45, Figure 12 · p. 46
  • Edge length correlated with pore-limiting diameter at r = 0.93 and pore volume at r = 0.88, producing a resolved trade-off curve rather than a qualitatively better material.The selectivity proxy was a geometric window score, not an adsorption calculation; the campaign stopped at the screening stage.Source: §C.4.4 · p. 46

C.4.5 Resource usage and provenance

  • The 80 production evaluations took under 5 min of computation, while the session used 80 min and $11.44 of LLM spend, or $0.14 per evaluated MOF.With this inexpensive evaluator, the agent rather than scientific computation was the bottleneck.Source: §C.4.5 · p. 47

C.5 Contact angle matching with RAISE

  • Óptima designed, executed, diagnosed, repaired, and interpreted a closed-loop RAISE laboratory campaign; its archived trace spans 11 operator turns.Campaign artifacts were preserved in the workspace throughout the session.Source: §C.5 · p. 48

C.5.1 Task definition and campaign implementation

  • The RAISE task targeted a 65° static contact angle within [64°, 66°], using ethanol and SDS concentrations spanning 0–60 v/v% and 0–1 w/v%.The operator requested two literature-derived warm starts and small, explicitly approved campaign increments.Source: §C.5.1 · p. 48
  • BO-MCP retained campaign state, while campaign programs submitted measurements and paused after each invocation for inspection and operator approval.A specialist validated and revised the campaign package with compile and interface checks, dry runs, and smoke tests.Source: §C.5.1 · p. 48

C.5.2 Campaign chronology

Óptima managed successive contact-angle campaigns, diagnosing measurement failures and improving the best measured angle without entering the target window. The session also documents campaign configuration, resource use, and how the agent constructed a separate flow-chemistry search space from operator-provided inputs.

C.5.2 Campaign chronology

  • The original campaign stalled below 20 v/v% ethanol after an infeasible suggestion was recorded as 180°; correcting the constraint and reseeding improved the best observation to 68.108° before a 67.755° one-shot measurement.The clean campaign used 18 unique valid observations after removing duplicates and three penalty rows, then completed five BO iterations without measurement failure.Source: §C.5.2 · pp. 48–49

C.5.3 Final campaign configuration

  • The final clean campaign used a GP surrogate with a Matérn kernel and qLogNoisyExpectedImprovement, while operator-supplied warm starts entered as ordinary observations.Óptima selected the remaining campaign settings; the operator supplied the target, tolerance, iteration budgets, and feasibility constraint.Source: §C.5.3 · p. 49

C.5.4 Failure handling and agent-initiated repair

  • The campaign initially treated infeasible formulations and missing measurements alike, submitting 180° penalties that distorted the search and biased it against unmeasured promising compositions.Óptima proposed correcting the search space for infeasibility and retrying no-value measurements up to twice before expiring them without an objective value; the expiration path was not exercised in the clean run.Source: §C.5.4 · pp. 49–50

C.5.5 Outcome and interpretation

  • Óptima attributed the dominant trend to ethanol improving wetting and interpreted SDS’s weak marginal effect above ∼0.6 w/v% as interfacial saturation and micellization.Three measurements of the same 0 v/v% ethanol, 0.60 w/v% SDS composition spanned 2.2°, motivating replication before a chemical conclusion.Source: §C.5.5 · p. 50
  • 67.755° was the session’s best contact angle, down from 71.403° but still outside the [64°, 66°] target window.Óptima recommended replicating the best formulation before drawing a chemical conclusion and changing the formulation if replicates confirmed a floor near 67–68°.Source: §C.5.5 · p. 50, Figure 13 · p. 51

C.5.6 Resource usage and provenance

  • The session used 148 LLM calls and cost $15.45; its reported trajectory comprised 27 evaluations, including 23 valid measurements and three penalty evaluations across the campaigns.Execution provenance was recorded in OpenTelemetry traces and campaign workspaces containing run context, evaluation logs, diagnostics, exports, scripts, and a runbook.Source: §C.5.6 · p. 51

C.6.1 Intended setup and chemical problem

  • For the flow-chemistry campaign, the operator supplied files defining available reagents, optimization bounds, stock solutions, and analytical constants, with no reaction-specific knowledge embedded beyond those inputs and the brief.Those inputs defined the available chemistry, permissible operating region, and online analytical method before the first experiment.Source: §C.6.1 · pp. 52–53

C.6.2 RoBridge: an agent-facing control layer for an autonomous chemistry platform

This section documents RoBridge as a stateful, agent-facing control layer for constructing and supervising a safeguarded RoboFlex Bayesian-optimization campaign, including its objectives, NMR analysis, and auditable state changes. It follows the campaign through an NMR configuration failure and a suspicious zero-yield, no-peak run, and describes limits in campaign records and plots as RoboFlex and the local supervisor updated at different times.

C.6.2 RoBridge: an agent-facing control layer for an autonomous chemistry platform

  • Named technicians certify physical layouts before chemistry, while structured setup and condition validation enforce chemical, vial, parameter, and hardware constraints before experiments reach the robot.The default mode permits only simulation experiments; moving to real hardware requires an explicit configuration change.Source: §C.6.2 · pp. 54–57
  • RoBridge exposes the platform through a strict, stateful HTTP API, leaving experimental design to callers while making robot capabilities, state, and refusals legible to remote agents.The bridge runs beside the platform on the robot PC and adds no user interface or optimization layer.Source: §C.6.2 · pp. 53–54
  • Nine explicit robot phases gate hardware requests, and responses report who or what is blocking progress, the next action, and a recommended polling interval.Requests in the wrong phase receive an explanatory refusal; expected run durations are learned from completed runs in the campaign.Source: §C.6.2 · p. 54
  • A hash-chained ledger attributes state changes to named actors and reconstructs measurement provenance, including autonomous failure classifications, fault signatures, recurrence counts, and tracebacks.Each ledger entry records the actor, action, structured payload, timestamp, state hashes, and predecessor hash.Source: §C.6.2 · p. 55
  • RoBridge checks experiment liveness and avoids campaign teardown when status is unknown; it automatically restarts most transient faults but escalates repeated faults and marks unfinished runs failed when campaigns disappear.The same fault twice in a row requires human intervention, and startup reconciliation places a robot whose process died mid-campaign into an error state.Source: §C.6.2 · pp. 57–58

C.6.3 Session 1: campaign construction and the yield/green campaign (24–25 July 2026)

  • Session 1 authored a RoboChem-Flex campaign package, ran six seed experiments plus fourteen iterations after an aborted attempt, corrected the NMR protocol to 19F acquisition, and inspected a zero-yield seed spectrum.The agent emitted a hypothetical instrument request for operator inspection before hardware use.Source: §C.6.3 · p. 59
  • The proposed campaign allocates 20 successful experiments to 6 informed seeds and 14 sequential Bayesian-optimization recommendations, maximizing yield with green score as a secondary objective.Seeds span catalyst families, oxidant identity, stoichiometric extremes, residence times, and light levels; batch size is one to allow feedback after each run.Source: §C.6.3 · p. 61
  • The green score rewards lower catalyst, TFAA, and oxidant loadings and lower combined photonic/residence-time burden, but is not a formal process-mass-intensity or life-cycle-assessment metric.It is a transparent, monotonic condition-efficiency score computable for each proposed experiment; platform data do not provide product mass or measured energy use per run.Source: §C.6.3 · p. 61
  • Real execution was gated by operator approval and an approved Robridge POST adapter; a later monitored launch showed one queued run and zero completed runs.The local smoke test generated a synthetic suggestion and result without using RoboFlex POST endpoints, while the supervisor was configured to stop after five consecutive suspicious zero/no-peak outcomes.Source: §C.6.3 · pp. 60, 62, 65
  • A hypothetical first-run Robridge request preview was generated for lab-collaborator review, but it was not sent to RoboFlex.The preview showed requests to start a campaign and submit the first seed experiment.Source: §C.6.3 · pp. 62, 65
  • The campaign uses RoboFlex NMR analysis to calculate yield from the target peak near -58 ppm within ±3 ppm, but leaves optional NMR settings to platform defaults.The live capability lists 1D EXTENDED+ as the default protocol, which the passages say may warrant lab confirmation, particularly if no-peak or zero-yield results appear.Source: §C.6.3 · pp. 66–67
  • The initial run failed during RoboFlex/NMR analysis because AcquisitionTime validation failed, so it produced no valid yield and was not submitted to BO-MCP.The parser error reported an invalid enumeration value and listed 0.4, 0.8, 1.6, 3.2, and 6.4 as allowed values.Source: §C.6.3 · p. 67
  • The corrected package mapped the Protocol field to 1D FLUORINE HDEC and sent AcquisitionTime 1.64, matching the updated constants.csv; local validation passed without real measurements.The earlier 1.6 override was removed after the instruction that the mismatch was between acquisition time and protocol.Source: §C.6.3 · pp. 69–70
  • R0044 completed, but yield, concentration, peak integral, and peak width were 0.0 and peak position was null; the monitor flagged a no-peak result.The zero/no-peak streak reached 1 in a campaign planned for 6 informed seeds plus 14 BO recommendations, with a stop rule after 5 consecutive such results.Source: §C.6.3 · pp. 70, 72, 73
  • R0044’s ^19F spectrum showed a dominant peak at ~ -76.47 ppm but no convincing target peak in the -61 to -55 ppm window.The target-region signal was about 3.7% of the main peak amplitude, and the rough area near -58 ppm was about 1.1% of the main-peak area.Source: §C.6.3 · p. 74
  • R0044’s automated zero-yield result was consistent with no detected peak near -58 ppm, rather than the previous protocol/acquisition parser error.The strong -76.47 ppm peak was not definitively assigned and could be an off-target fluorinated species, reagent, byproduct, or background component.Source: §C.6.3 · pp. 74–75
  • The experiment log covered visible runs R0044–R0052, but R0052’s completed 11.56% yield had not yet been matched with local green-score and submission-analysis fields.The log snapshot could be regenerated after the supervisor finished processing subsequent updates.Source: §C.6.3 · p. 75
  • 30.04% was the current best yield from R0045, with BO run R0051 close behind at 27.64%.The improvement curve contained 8 analyzed results; R0052 was excluded because it had not yet appeared in the supervisor’s analyzed/submitted results file.Source: §C.6.3 · p. 76

C.6.4 Session 2: campaign continuation and the yield-only refocus (25–29 July 2026)

This section traces the campaign’s continuation through measurement and analysis failures, its shift from a yield-dominant scalarized objective to yield-only optimization using historical results, and a later unresolved run. It covers the observed yield gains and high-yield region, as well as campaign attempts that stopped without a recorded completion.

C.6.4 Session 2: campaign continuation and the yield-only refocus (25–29 July 2026)

  • 58.81% yield (R0067) was the campaign’s best measurement after the yield/green campaign reached 20 observations and was refocused on yield alone.The session continued from the preceding session’s nine valid measurements.Source: §C.6.4 · p. 76
  • The autonomous run stopped safely when RoboFlex marked R0060 pass=false, submitting no BO result and pausing the campaign despite a finite 25.03 yield.The script avoided contaminating the BO model; the reported result was not the anticipated zero/no-peak failure pattern.Source: §C.6.4 · pp. 77, 79
  • After the operator chose a retry, the workflow reused the failed suggestion’s experimental conditions with a new sample and would submit the result only if the retry passed.The retry continuation began, but these passages provide no retry outcome.Source: §C.6.4 · p. 79
  • The BO backend used expected improvement on a geometric-mean desirability scalarization, weighting yield at 0.8 and green score at 0.2 rather than optimizing a Pareto front.Thus it favored yield while still accounting for green score.Source: §C.6.4 · pp. 80–82
  • Green score was computed from candidate conditions, rewarding lower catalyst, TFAA, and oxidant use and lower combined light-intensity/residence-time burden.The four green-score penalty terms were equally weighted, and photonic burden combined light intensity with residence time.Source: §C.6.4 · pp. 80–81
  • After 18 valid results, a BO-MCP read timeout while generating the next suggestion safely paused the campaign with RoboFlex idle and no pending measurement #19 suggestion.A patched resume path was then used to continue from the current 18 results, but the run stopped after measurement #19 failed analysis.Source: §C.6.4 · pp. 82–83
  • Measurement #19 produced a yield-like value of 27.04 but failed RoboFlex analysis, so it was not submitted to BO-MCP and measurement #20 was not attempted.The campaign paused and RoboFlex returned to idle/awaiting-run state.Source: §C.6.4 · p. 84
  • Two BO-suggested points near 16–17 minutes residence time failed analysis, while rerunning the earlier point passed with yield 48.51, leaving intermittent QC failure versus a systematic issue unresolved.The report proposed rerunning measurement #19 once and submitting it only if it passed, or inspecting raw NMR/analysis criteria before continuing.Source: §C.6.4 · p. 85
  • RoboFlex reported the failure flag; a finite yield and detected peak suggest an analysis/QC failure, not a hardware crash, but the API did not reveal the exact cause.The script’s role was to stop and withhold failed results from BO-MCP; peak-quality issues are possible but unconfirmed.Source: §C.6.4 · p. 87
  • 0.2152 ppm exceeded the 0.2 ppm maximum peak width, so retry R0064 failed QC despite a detected target-region peak and finite yield estimate.Two attempts for the same condition failed for excessive peak width; the third retry passed.Source: §C.6.4 · pp. 89–91
  • 45.09% yield with green_score 85.53 was recorded on measurement #19’s final retry, which passed NMR QC.The target peak width was 0.1102 ppm and pass=true.Source: §C.6.4 · p. 91
  • 0.00% yield with pass=true and peak_found=false was recorded for measurement #20, after which the planned 20-result campaign was complete and paused.The single zero/no-peak result triggered an alert but was submitted as valid, and the campaign exited successfully.Source: §C.6.4 · pp. 91–92
  • 48.51% yield with green_score 82.50 on measurement #17 was the continuation’s best observed yield.This was the retry of R0061.Source: §C.6.4 · p. 92

Chemical interpretation

  • 48.51% yield was the campaign’s best result, at experiment #17 / R0061, with a green score of 82.50.The best-yield condition used Ru bpy Cl / py NO, 50% light, and about 16.43 minutes’ residence time.Source: §C.6.4 · p. 97
  • 45.09% yield with a green score of 85.53 at #19 was a greener high-yield compromise, only about 3.4 percentage points below #17’s yield.The passage characterizes #19 as having a slightly greener score than #17.Source: §C.6.4 · p. 97
  • Several productive-region measurements initially failed NMR quality control because of broad peaks, but reruns eventually passed and supported the high yields.The assessment recommends inspecting failed-QC results rather than accepting them blindly; retrying once, or twice when finite and reproducible, was considered reasonable.Source: §C.6.4 · p. 97
  • Experiment #20 produced 0 yield with a valid pass but no target peak, suggesting 25% light may fall below the photon flux needed for the reaction.Its conditions were near the productive reagent and residence-time region, making the lower light intensity the salient difference noted in the interpretation.Source: §C.6.4 · pp. 97–98
  • The productive region favored Ru bpy Cl / py NO, moderate reagent excess, 50% light, and roughly 16–18 minutes’ residence time.The campaign summary places catalyst loading near 0.0012 equiv, TFAA at 1.55–1.62 equiv, and oxidant at 1.30–1.44 equiv; 2-minute residence was too short, while 100% light did not improve yield and 25% may be insufficient.Source: §C.6.4 · pp. 94, 95, 96, 98

Yield-only refocus

  • The prepared follow-up workflow would maximize yield alone, seed from 20 valid results, and allow three retries per suggestion for stochastic NMR failures; it was not started.The new objective uses yield_percent with bounds [0, 100], excludes green_score as an optimization objective, and awaits confirmation before campaign start.Source: §C.6.4 · pp. 98–99

C.6.4 Session 2: campaign continuation and the yield-only refocus (25–29 July 2026)

  • The continuation used a focused block because existing data showed a high-yield region, with reassessment planned after five new measurements.The proposed review included best yield, replicate consistency, clustering of suggestions, NMR pass/fail rate, and whether the model improved or plateaued.Source: §C.6.4 · pp. 100–101
  • The overnight yield-only campaign was seeded with 20 valid results, capped at eight new valid measurements, and allowed up to three NMR/QC retries per suggestion.No new RoboFlex campaign was created; the continuation used the existing active hardware campaign.Source: §C.6.4 · pp. 103–104
  • 58.81% was the new best yield in measurement #21, up from the previous best of 48.51%.The result was completed and submitted to the yield-only BO campaign.Source: §C.6.4 · p. 104
  • Measurement #21 increased TFAA and catalyst loading while retaining the successful catalyst, oxidant, light, and residence-time region.The retained region was Ru bpy Cl / py NO / 50% light / ~15–17 min residence.Source: §C.6.4 · p. 105
  • Removing the green objective freed the optimizer to raise reagent and catalyst loading, with higher TFAA a plausible contributor to the yield gain.TFAA rose toward 2.0 while oxidant slightly decreased and light stayed unchanged; the passages present this as an interpretation, not a causal finding.Source: §C.6.4 · pp. 105–106
  • Yield increased from ~48.5% to 58.81% in yield-only BO, which shifted away from the greener low-catalyst/lower-TFAA region toward higher catalyst and TFAA loadings.The candidate kept 50% light and the productive Ru bpy Cl / py NO combination. Because catalyst and TFAA changed together, their individual effects cannot be isolated.Source: §C.6.4 · pp. 105–106
  • Measurement #22 tested a more aggressive candidate but failed with a null result and a non-retryable analysis error, so no BO result was submitted.The error differed from earlier NMR/QC failures with finite yield evidence; the run stopped safely under the existing retry policy.Source: §C.6.4 · pp. 106–107
  • A revised policy treated the analysis error as retryable up to three times while RoboFlex remained healthy, but the continuation later stopped when #27 failed before analysis.The #27 failure was distinguished from retryable NMR-analysis failures.Source: §C.6.4 · pp. 109–110
  • Yield-only results #21–#26 were 58.81%, 54.50%, 0.00%, 0.00%, 45.79%, and 0.00%, respectively.Result #22 was a successful retry of a prior analysis error.Source: §C.6.4 · p. 110
  • The clean campaign retained 20 original valid historical results plus R0067 at 58.81% and explicitly excluded experiments R0068–R0074.The technician asked that experiments from R0068 onward be discarded because failures and questionable 0.00 yields began there.Source: §C.6.4 · p. 111
  • The continuation began after preflight found RoboFlex in hardware mode, running, and awaiting a run with no active runs queued.The new clean campaign continued against the technician-prepared RoboFlex campaign.Source: §C.6.4 · pp. 111–112
  • Repeated polling errors for R0075 and a failed status check suggested a RoboFlex API/connectivity or server-availability issue, not necessarily a chemistry or run failure.After polling was stopped, no further runs were submitted and R0080 was not marked completed or failed in BO-MCP.Source: §C.6.4 · p. 112
  • 26 successful/submitted BO results were exported; R0080 was excluded because it remained unresolved and not submitted when polling stopped.The export covered the clean yield-only campaign.Source: §C.6.4 · p. 113

C.6.5 Executed experiments

The final campaign record contains 23 experiments, while seven additional runs were excluded for unusable analyses, supersession, or an unavailable platform. The cost and mass comparison uses defined accounting boundaries that distinguish campaign costs and reaction inputs from omitted process steps.

C.6.5 Executed experiments

  • 23 experiments make up the final campaign record; seven additional runs were excluded because of unusable analyses, supersession, or platform unavailability.Each recorded run used a 650 µL slug at 100 mM substrate, containing 65 µmol (13.60 mg) of limiting reagent.Source: §C.6.5 · p. 113, Table 19 · p. 114

C.7.1 What is counted, and how

  • Campaign A was human-directed, while Campaign B was constructed, executed, and monitored by Óptima; the campaigns used the same transformation and hardware.The operator supervised Campaign A and stopped Campaign B after 23 experiments.Source: §C.7.1 · p. 115
  • Campaign cost includes each run’s full recorded reagent and solvent load at research-scale list prices, but excludes operator time because it was not measured for either campaign.The analysis reports total campaign cost, per-experiment cost, and mass efficiency; no recovery, recycling, or bulk discount is assumed.Source: §C.7.1 · p. 115
  • Carrier and cleaning solvent account for approximately 97% of experiment mass, so they are excluded from mass accounting but retained as costs.Each run uses 25 mL of acetonitrile for transport and line cleaning; those requirements are specific to serial-screening operation and are not required in the same form at scale.Source: §C.7.1 · p. 115
  • Mass-intensity figures describe 0.65 mL reactions with in-line yields and omit scale-up, work-up, quench, extraction, and purification.They are lower bounds for a complete process and are not directly comparable with literature PMI values based on isolated, purified product.Source: §C.7.1 · p. 115

C.7.2 Cost of the campaign and of an experiment

The agent-directed campaign used fewer experiments and less starting material, lowering its campaign cost, although inference added substantial expense. The campaigns differed in length, and the authors do not claim that either strategy searched more effectively.

C.7.2 Cost of the campaign and of an experiment

  • Campaign B cost 43% of Campaign A on consumables while using 46% of its experiments and 39% of its starting material; including inference, it remained 13% cheaper overall.Inference cost $109.55, more than the chemistry it directed; Campaign B’s fully loaded cost was €8.81 per experiment.Source: §C.7.2 · p. 115, Table 21 · p. 116
  • At the agent’s €98.00 consumable spend, Campaign A had reached 63.9% yield after 18 experiments, versus 58.8% for Campaign B after 23.Truncated at 23 experiments, Campaign A had spent €115.73 and also reached 63.9%; its first-23-run best came from initialization, and it did not improve until run 29.Source: §C.7.2 · p. 115
  • The authors make no claim that either strategy searches more effectively because the campaigns differed in length and a single pair cannot support that conclusion.Campaign A received approximately 2.2 times as many experiments as Campaign B.Source: §C.7.2 · p. 115

C.7.3 Mass efficiency

Mass-efficiency rankings depend on whether reaction solvent is included and whether metrics describe an optimum or an entire search. Campaign B used less reagent mass per product on a solvent-free basis and had better campaign-level mass-efficiency metrics, but the comparison is bounded by accounting choices and is not a controlled benchmark.

C.7.3 Mass efficiency

  • PMI includes reaction solvent, but equal 100 mM substrate concentrations made that solvent 87–92% of input mass at the optima, limiting insight into stoichiometry.Solvent-free metrics expose the conversion–stoichiometry trade-off; Campaign B was fixed at 100 mM, while Campaign A explored 100–200 mM and reached its optimum at 100 mM.Source: §C.7.3 · p. 117
  • With solvent included, Campaign A’s optimum had the lowest PMI, 49.0 versus 56.3 and 67.6 for Campaign B’s two conditions.Reaction solvent mass was identical and dominated input mass at all three optima, so this ranking was primarily determined by yield.Source: §C.7.3 · p. 117, Table 22 · p. 118
  • At the solvent-free optimum boundary, Campaign B’s runs 17 and 21 had RME of 18.0% and 19.6%, versus 15.3% for Campaign A; solvent-free PMI was 5.55 and 5.09, versus 6.53.The agent selected leaner stoichiometry: 4.1 and 4.4 total reagent equivalents at runs 17 and 21, compared with 6.9 for Campaign A.Source: Table 22 · p. 118, §C.7.3 · p. 119
  • Campaign B’s campaign-level RME was 9.44% versus 3.60% for Campaign A, and solvent-free PMI was 10.6 versus 27.8.These search-level metrics charge all experiments against product formed; Campaign A had 27 zero-yield experiments, compared with two in Campaign B.Source: §C.7.3 · p. 119, Table 23 · p. 119

C.7.4 Electricity

  • Electricity contributed less than 2% of either campaign’s fully loaded cost at the adopted tariff and was marginally higher for Campaign B.Campaign A occupancy was reconstructed from timestamps; Campaign B’s 34 h occupancy was measured from the agent trace.Source: §C.7.4 · pp. 119–120

C.7.5 Limitations

  • The comparison covers two campaigns that differed in search space, initialization, length, and prior knowledge, so it is not a controlled benchmark of human-directed versus autonomous BO.The campaigns reached different reaction conditions; yields were measured in-line on unpurified mixtures, and inference pricing reflects one model at one point in time.Source: §C.7.5 · p. 120
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