Koji
Ochiai†
a,
Yuya
Tahara-Arai†
bcd,
Akari
Kato
ade,
Kazunari
Kaizu
af,
Hirokazu
Kariyazaki
g,
Makoto
Umeno
h,
Koichi
Takahashi‡
*ai,
Genki N.
Kanda‡
*adj and
Haruka
Ozaki‡
*bdk
aLaboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research, 6-7-1 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. E-mail: ktakahashi@riken.jp
bBioinformatics Laboratory, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
cPhD Program in Humanics, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
dLaboratory Automation Suppliers' Association, 2-1-8 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
eResearch DX Foundation Team, RIKEN Data and Computational Sciences Integration Research Program, 6-7-1 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
fCell Modeling and Simulation Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan
gRobotics Division, YASKAWA Electric Corporation, 2-1 Kurosaki Shiroishi, Yahatanishi-ku, Kitakyushu, Fukuoka 806-0004, Japan
hBAIKEIDO LLC, 3-8-1 Asano, Kokurakita-ku, Kitakyushu, Fukuoka 802-0001, Japan
iGraduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa-shi, Kanagawa 252-0882, Japan
jDepartment of Robotic Science, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: genki.kanda@tmd.ac.jp
kLaboratory for AI Biology, RIKEN Center for Biosystems Dynamics Research, 6-7-1 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. E-mail: haruka.ozaki@riken.jp
First published on 19th August 2025
The automation of experiments in life sciences and chemistry has significantly advanced with the development of various instruments and artificial intelligence (AI) technologies. However, achieving full laboratory automation, where experiments conceived by scientists are seamlessly executed in automated laboratories, remains a challenge. We identify the lack of automation in planning and operational tasks—critical human-managed processes collectively termed “care”—as a major barrier. Automating care is the key enabler for full laboratory automation. To address this, we propose the concept of self-maintainability (SeM): the ability of a laboratory system to autonomously adapt to internal and external disturbances, maintaining operational readiness. This ability is inspired by the homeostasis, resilience, autonomous state recognition, and adaptability seen in living cells. A SeM-enabled laboratory features autonomous recognition of its state, dynamic resource and information management, and adaptive responses to unexpected conditions. This shifts the planning and execution of experimental workflows, including scheduling and reagent allocation, from humans to the system. We present a conceptual framework for implementing SeM-enabled laboratories, comprising three modules—Requirement manager, Labware manager, and Device manager—and a Central manager. A laboratory design that is aware of SeM not only enables scientists to execute envisioned experiments seamlessly but also provides developers with a design concept that drives the technological innovations needed for full automation.
While the integration of robotic automated experiments and AI has enabled the automation of iterative optimization processes, these systems still rely heavily on human involvement for what we propose to define as “care.” Care refers to the human-managed tasks required to maintain and support automated systems, encompassing a range of essential responsibilities at both the planning and operational steps of automated laboratories (Fig. 1). In the planning step, care includes translating experimental objectives into machine-readable workflows and scheduling resources such as equipment and reagents. In the operational step, it involves preparing and cleaning up experiments, restocking supplies, monitoring system states, and addressing errors or unexpected conditions. For example, humans must ensure compatibility between workflows and equipment limitations, such as splitting a 200 μL aliquot into two 100 μL portions to align with equipment constraints. Additionally, tasks like verifying equipment availability and adapting workflows to real-world constraints remain outside the scope of current automation capabilities, leaving these responsibilities as a bottleneck in achieving fully autonomous scientific discovery.
Care is indispensable for making experimental protocols feasible under laboratory conditions, bridging the gap between conceptual designs and their practical execution. Usually, experimental protocols are abstract and must be adapted to the physical constraints and conditions of the laboratory: Even with the same conceptual protocol, the operational protocol can differ based on the laboratory environment and setup, due to variations in equipment, space, or resources. Such adjustment processes requires intervention of human managers and operators, primarily because (1) most of the conventional laboratory automation systems lack the ability to recognize their environments and adapt to them, (2) these systems are designed to operate within predefined constraints, relying on user-provided inputs such as initial setups and experimental conditions, (3) the dynamic nature of laboratory environments, where conditions can shift due to concurrent experiments or resource usage, necessitates manual intervention to prepare the setup immediately before execution.
This reliance on human care constrains the capabilities of automated laboratories, limiting their application primarily to repetitive or screening-based experiments including closed-loop experimentation. In the planning step, the dependency on human care restricts the range and complexity of experiments that can be executed. For example, when introducing new experiments, reagents, and labware, robotic protocols are iteratively refined through trial and error until human operators ensure that workflows are feasible, avoiding flexible modifications in experimental conditions, addition of newly performed experimental protocols, and parallel execution of multiple experiments. In the operational step, the dependency on human care (e.g. handling errors) limits the number of experiments that can be executed simultaneously, creating a bottleneck in throughput. As a result, the full potential of automation remains unrealized, with current systems unable to perform the adaptive and flexible processes required for more diverse and complex scientific discovery.
In an ideal automated laboratory, experiments are conducted entirely without human intervention. To achieve this, not only experimental operations but also the tasks we define as care must be fully automated. This includes addressing dynamic and unforeseen changes in the laboratory environment, ensuring that experimental processes can continue progressing even in the face of unexpected situations. Such a laboratory would require a new design paradigm in which the system itself autonomously acquires information, makes adaptive decisions, and manages its environment. This approach moves beyond the current reliance on humans to oversee and validate each step, paving the way for a more flexible and truly autonomous scientific discovery process.
In this vision, the entire laboratory functions as a cohesive system, akin to a single, integrated workstation. Instead of viewing individual devices as isolated units, the laboratory operates as a unified whole. Equipment management, labware tracking, waste disposal, and overall status monitoring are automated and coordinated as part of the system. By transferring these responsibilities—conventionally managed by humans—to the automated laboratory itself, the burden on human operators is eliminated. This enables the system to conduct not only repetitive or screening-based experiments but also highly complex, non-standardized workflows that require adaptability and creativity, fulfilling the broader potential of scientific automation.
Implementing automations of care through bottom–up extensional engineering is presumably difficult because there are no limits to what can be done. For instance, if there are multiple locations where a tube containing ethanol could be placed, a mechanism could be created to check each of them. However, such a process would be specific to a particular experiment and would require adjustment and redevelopment each time the type of experiment changes. This approach lacks scalability and adaptability for dynamic laboratory conditions.
Self-maintainability (SeM) – the system's ability to maintain itself to the state where it can function effectively in environments subject to material consumption, equipment wear, and potential operational disruptions caused by external disturbances.
Conventional approaches to laboratory automation have primarily focused on repeating a single protocol multiple times (Fig. 2A). However, an ideal automated laboratory should be capable of automatically conducting a wide variety of daily experiments for multiple users (Fig. 2B). Such an automated laboratory can be characterized by three essential requirements. First, it must integrate multiple devices that operate in concert (Fig. 2C). Second, to accommodate diverse demands, the laboratory must flexibly incorporate and remove various elements including samples, labware, reagents, waste, and human operators (Fig. 2D). Third, it must function amid uncontrollable changes, such as ongoing experimental processes, environmental fluctuations, and human intervention (Fig. 2E). Historically, humans have provided the care required to address these challenges, but this care can be automated by incorporating processes analogous to those in living cells—specifically, “intake,” “discharge,” and “metabolism.” Consequently, the laboratory must be able to maintain its own function autonomously: regardless of resource consumption by ongoing experiments, sudden environmental changes, or unforeseen interruptions, it should continue to accept and execute experiments. This ability is here defined as SeM (Fig. 2F).
The idea of SeM can be used to provide a holistic framework for designing systems capable of autonomously adapting to and mitigating real-world challenges (Fig. 3). Existing experiment automation, including most closed-loop experiment systems, has almost no SeM and relies on human care, whereas automated laboratories with high SeM can be operated with low burden on humans. In other words, today's automation requires users to think about things that are not important to them (e.g., where to place plates and tube racks on the desk, where to store consumables) each time an experiment is performed. Laboratory's SeM improvements will enable automation of experiments without the need for human effort or time for such matters. For example, tasks currently performed during the planning step, such as translating experimental objectives into machine-readable workflows and scheduling equipment and reagent use, would be autonomously managed by the system. Similarly, operational step tasks like preparing and cleaning up experiments, restocking supplies, monitoring system states, and resolving errors would be handled automatically. SeM not only eliminates repetitive human manual interventions but also enables laboratories to execute more complex and flexible experiments, overcoming the current bottlenecks in scalability of experiment type and adaptability. Furthermore, SeM can bridge the gap in expertise among human scientists, enabling researchers from different fields to conduct experiments effectively without requiring specialized operational knowledge. For instance, when a chemist seeks to test a hypothesis in another field such as biology, they may lack the tacit laboratory knowledge required to specify each cell-culture step or DNA-analysis parameter; an SeM system can translate that high-level objective into domain-appropriate, concrete procedures.
These differences suggest that, in SeM-enabled laboratories, the roles of users and the system are redefined. In existing experimental automation systems, users are responsible for collecting and providing information, and the system determines its actions based on the information provided. Consequently, such systems had to rely on human care for various tasks required to complete an experimental order, such as designing and implementing new experimental protocols, responding to changing conditions, and handling errors. In contrast, SeM-enabled laboratories free users from the need to know the internal conditions of the laboratory when making experimental orders. Instead, the SeM-enabled laboratory autonomously collects the necessary information to fulfill the order—without waiting for user instructions—, recognizes the current state, adapts its responses accordingly, and executes automated experiments.
Similarly, tasks related to higher-level experiment management, such as adjusting schedules or adding new experiments, which were previously the user's responsibility, are now handled by the laboratory itself in SeM-enabled laboratory. For instance, in the case of a schedule change, if one of the sample plates is dropped, the user may be asked whether to cancel the experiment or to continue with the remaining plates. Depending on the user's decision, if the experiment is aborted, the laboratory will clean up and discard the samples. If it is continued, unnecessary steps in the protocol (i.e. the subsequent planned experimental steps for the discarded sample plate) will be omitted to adapt to the situation. Additionally, for new experimental orders, the laboratory autonomously manages and adjusts the schedule. For example, it can use available device time to initiate another cell culture or reallocate operations to accommodate a sudden visitor. Noted that logging critical decision points, criteria, and outcomes, coupled with interfaces allowing human intervention or confirmation, ensures that the system remains visibly under human oversight. This transparency facilitates an incremental transition from human-intensive management to greater autonomy, thus systematically building trust in the SeM-enabled system.
To realize this ability, it is necessary to redesign the devices and its control system for automated laboratories. First, a mechanism is needed to actively gather additional information as necessary, such as details of experimental conditions, sample priorities, or deadlines, because users are assumed to be unable to fully convey their requirements when making an experimental order. Second, a system that actively collects information about the laboratory's state through sensors is essential. Users often lack complete information about the automated laboratory, such as available equipment, labware, or ongoing experiments. Moreover, the laboratory's state can fluctuate constantly due to internal and external disturbances. Third, it is required to flexibly control the automated experiment systems and robots based on the recognized states, demanding the robot controllers to respond to on-demand motion commands rather than executing predefined actions such as teaching and playback. Fourth, while conventional systems treat sensor data and human input separately, a software architecture is required to handle both sources as they jointly influence experimental changes. Fifth, all information in the laboratory—from users to devices to labware—must always be available, even during experiment execution, to ensure the system can adapt to constantly changing states and accommodate new experimental orders or schedule changes.
Hereafter, we will consider the architecture to realize the SeM-enabled laboratory in more detail. We believe that three modules (Requirement manager, Labware manager, and Device manager) and a Central manager that controls them are necessary to realize the SeM-enabled laboratory (Fig. 5).
The Requirement manager is a module that communicates interactively with the user to obtain and manage the requirements of an experimental order. To conduct a new experiment in conventional experimental automation systems, a user must (1) create a new protocol with detailed specifications, (2) verify that the protocol achieves the expected behavior using empty labware when necessary, and (3) confirm that the required conditions are met at the start of the protocol before initiating it. In a SeM-enabled laboratory, on the other hand, the SeM-enabled laboratory autonomously plans and determines the details of the experiment with reference to the state of the laboratory. Because it is not assumed that users can state all the information required to complete the experimental order at once, the Requirement manager proactively collects additional information on the requirements for the orders through an interactive interface, such as chat.
The Labware manager is a module that manages the current status of the laboratory by recognizing the state of the laboratory through sensing to deal with disturbances that create differences between the assumed and actual laboratory. Sensing is essential in physical space where external disturbances cannot be eliminated, making it impossible to predetermine the state of all objects. Even if a part of the experimental devices is isolated from external factors, some parts of the laboratory must remain open to external interactions to facilitate the entry and exit of consumables. Consequently, external disturbances may occur, such as misplaced consumables or variations in consumable shapes due to lot-to-lot variability. Image recognition is considered useful for recognizing conditions in the laboratory. Recent studies, such as You Only Look Once (YOLO)29 and ot2eye,30 which applied YOLO to labware recognition, can be used to realize SeM. Experimental systems also need the ability to estimate the current state while using past observations. For example, even if a tube is now out of the camera's field of view, it should remain at the last observed position, or the amount of reagent should have decreased since it has been dispensed.
The Device manager is the module that translates the actions determined by the Central manager into specific instructions for the robot or device. The Device manager encompasses device-specific programs to control various devices and robots in a SeM-enabled laboratory. Depending on the state recognized by the Labware manager, the Central manager determines the actions required to achieve a desired state. The Device manager must be flexible enough to adapt to such instructions by the Central manager. While conventional solutions such as dedicated application programming interfaces (APIs) can specify locations in an automated workstation using symbolic position specification. However, in a SeM-enabled laboratory, where multiple devices and robots are used, such solutions as they complicate cross-device coordination (e.g., object transfer and liquid handling across equipments) and make it difficult to handle unexpected situations caused by external disturbances (e.g., misplaced consumables). To address this, the Device manager requires parametric instructions that can flexibly specify positions in physical space, enabling coordination across devices and adjustments for unexpected states. Recently, motion generation AI for robots such as RT-2 (ref. 31) has been studied, and it is expected that this technology can be applied to SeM-enabled laboratories.
These three modules are controlled from a higher level module, the Central manager, which is intended to be a generative AI. The Central manager uses information from users and sensors through the Device manager and the Labware manager to design and proceed experiments through a trial and error process. Trial and error here is not solely mechanical (experiment operation in Appendix B) but also includes resource management, such as allocation of consumables and adjustment of equipment usage time with other experiments (experiment design in Appendix B). As shown in Appendix A, in order to conduct an experiment, it is necessary to determine the experimental design by estimating the necessary resources and repeatedly checking and reserving resources several times. Until now, these tasks have been performed by humans, but with a SeM-enabled laboratory, these tasks are performed by the Central manager.
A SeM-enabled laboratory is realized through the coordinated operation of four modules: the Requirement manager, Labware manager, Device manager, and Central manager. To illustrate the differences between conventional and SeM-enabled laboratories, consider the following scenario. In conventional automated systems equipped with an automated pipetting machine, if a user wants to “add 2 mL of cell culture medium to all wells of this plate,” they must perform the following care: (1) check the available time of the pipetting machine, (2) make a reservation, (3) prepare medium-containing tubes, (4) place the tubes on the deck of the pipetting machine together with the plate, and (5) create and execute an operation program that matches the placement of the tubes.
In contrast, in a SeM-enabled laboratory, when a user requests, “add 2 mL of cell culture medium to all wells of this plate” via the Requirement manager, the Central manager first collaborates with the Labware manager to reserve an automated pipetting machine and medium-containing tubes. Next, the Central manager uses the Device manager to operate a robotic arm to move the plate and tubes to the automated pipetting machine. Finally, the Central manager operates the automated pipetting machine, again via the Device manager, to transfer medium from the tube to the plate. In this way, SeM-enabled laboratories can automate tasks that were previously performed by human operators. More implementation details are provided in Appendix B.
In this paper, we addressed the critical yet often overlooked concept of care—the human-managed tasks essential for maintaining and supporting automated systems. By proposing SeM as a key enabler of fully automated laboratories, we redefined the automated laboratory as a holistic, adaptive system capable of managing dynamic environments and responding to unexpected disturbances without human intervention. SeM enables laboratories to internalize tasks conventionally performed by humans—such as resource management, error handling, and workflow adaptation—bridging the gap between human intentions and the practical execution of automated experiments. The concept of SeM-enabled laboratories marks a paradigm shift, treating the entire laboratory as a unified, self-regulating entity. We also explored the technical considerations necessary to redesign devices and their control systems to achieve SeM-enabled laboratories. We believe SeM-enabled laboratories not only eliminate bottlenecks stemming from human dependencies but also extend the capabilities of automation to encompass complex, flexible, and diverse experimental workflows, paving the way for a new era of autonomous scientific discovery.
SeM is also crucial for the application of AI-based scientific research, which has recently attracted attention in the field of machine learning, to the biological and scientific fields. Lu et al. recently developed “AI Scientist” and demonstrated the automation of science in the field of machine learning.52 The AI Scientist automates the whole processes of machine learning research including knowledge retrieval, hypothesis generation, validation experiments, data analysis, paper writing, and peer review. The machine learning field is a good benchmark for automation in science as an early demonstration because the experimental process is completed inside the computer. On the other hand, applying this kind of framework to experimental science fields such as life science and chemistry presents a unique challenge. It requires enabling AI systems to autonomously execute experimental processes in the physical space without human intervention or care. SeM-enabled laboratories are fundamental to overcoming this challenge, providing the infrastructure necessary to realize fully autonomous experimental research.
For training, teleoperation data is recorded where a person operates the robot in a joint space. During operation, the learned model outputs control signals at 50 Hz, enabling precise movements such as opening a translucent condiment cup and slotting a battery, for example.
Since 2023, the potential for general-purpose robots powered by large-scale models has expanded rapidly. With the advent of VLA models, it is becoming increasingly realistic for robots to autonomously operate while observing their environment, based on natural language instructions—eliminating the need for task-specific programming that was previously required.31,54–58
In traditional programming, the behavior of the system is determined by the architecture, but in machine learning, the dataset design determines the behavior. For example, Chain of Thought is realized by devising training data, not by special software structures59.
This chapter discusses what kind of datasets are necessary for experiment automation from two perspectives: (1) experiment operation: the process of generating behavior based on experimental procedure, and (2) experiment design: the process of creating experimental procedures.
● Labware handling: dataset to build on general object manipulation knowledge, but also to learn lab-specific precautions (e.g., keeping plates, tubes, pipettes, etc. horizontal, grasping the top of tube to prevent heat transfer).
● Error handling: collect detection and recovery actions, such as re-grasping when a grasp is missed or interrupting and calling someone if a sample is dropped.
● Replenishment/disposal request: a data set that includes the process from requesting a person to replenishment/disposal, to receiving/removing the item, checking it, and re-requesting it if necessary.
● Use of operator reports: a data set of processes that dynamically adjusts execution plans based on reports such as “reagent refilled”.
● Inventory check: a dataset that includes a series of steps from using a mobile robot's camera to check the consumable shelf and incubator to determine the current inventory.
● Long-term experiment management: the robot is trained to accurately continue a multi-step procedure based on the execution history. Evaluate whether the procedure can be executed without skipping steps or repeating the same part of the procedure.
In particular, in the case of experiments, the following context-adaptive procedure generation is required:
● Description of transportation routes consistent with the physical placement of consumables
● Adjustment of task timing based on available equipment and their free time slots
● Reproduction of past experiments
To improve the accuracy of planning based on these factors, a dataset is needed that enables evaluation not only of adherence to experimental instructions but also from the following perspectives:
● Determining whether the procedure is feasible based on the laboratory's state, including consumables and reservation status for the procedure
● Adherence to standard protocols (e.g., those described in publications or commercial kits)
● Adherence to procedures previously executed in the same laborator
To enable such planning, interactive procedure generation using a VLA model is required. The VLA model generates executable and optimized procedures by referring, as needed, to the current laboratory state, available equipment, past experimental results, and literature, while also confirming the user’s intentions when necessary. For training the VLA model, a dataset that captures the entire flow of procedure creation should be constructed—for example, logs that record both chat history between researchers and technical staff and the corresponding access history to resource management systems and reference materials. This would allow users to avoid designing procedures from scratch; instead, by simply conveying the differences from a published protocol or a past experiment, the VLA model could adjust the procedure accordingly.
In the process of procedure creation, the required quantities of consumables are estimated, and reservations or allocations are made accordingly. If stock is insufficient, actions such as additional ordering are autonomously incorporated into the plan. This process could likely be learned through self-supervised learning, provided that the task of determining whether a procedure is feasible based on the laboratory's state—including consumables and reservation status—has already been achieved.
Furthermore, it is important to establish a mechanism for structuring environmental information in the laboratory so that it can be utilized during experiment planning and execution. Traditional automation systems have had difficulty directly acquiring environmental states, often relying instead on inference from operation history. In contrast, the VLA model can directly perceive the environment through modalities such as vision, allowing the robot to manage state explicitly by writing information back into the environment.
Specifically, the following approaches are taken:
● Attaching notes or labels to labware to manage its contents and status
● Designing rules and placement guidelines for these labels during the procedure generation stage, so that robots can perform the labeling during execution
● Incorporating such “writing to the environment” actions into the dataset from both the experimental operation and experimental design perspectives
Experimental design—generating flexible and explainable protocols while referencing both instructions and the environment—is one of the central elements for realizing SeM.
For implementation, we expect that starting with the automation of experiment operations, which have short individual durations, will facilitate data collection, learning, and evaluation. Furthermore, through this process, it will become possible to identify procedure formats that are easier for the VLA model to translate into operation, allowing the experiment design process to be adjusted accordingly to fit those specifications.
Footnotes |
† First authors (equal contribution). |
‡ Contact authors (equal contribution). |
This journal is © The Royal Society of Chemistry 2025 |