Miniature compartment system for in vitro fertilization (IVF)

Abstract

Embodiments of the present disclosure relate to micro compartment systems for in vitro fertilization (IVF). The present disclosure generally relates to micro-chambers for automated cell culture under controlled environmental conditions. In some implementations, a system includes a first chamber, a second chamber, and a control subsystem. The control subsystem detects a first environmental condition associated with the first chamber and a second environmental condition associated with the second chamber. The control subsystem supplies a first airflow to the first chamber at least based on the first environmental condition and the first airflow pattern to adjust the first environmental condition to a first target environmental condition. The control subsystem supplies a second airflow to the second chamber based at least on a second environmental condition and a second airflow pattern to adjust the second environmental condition to a second target environmental condition.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 660,263, filed June 14, 2024, entitled “MINIATURIZED AUTOMATIC INCUBATOR SYSTEM,” the entire disclosure of which is incorporated herein by reference for all purposes. TECHNICAL FIELD

[0003] The present invention relates to devices for cell culture, and more specifically to an incubator system that controls environmental conditions for cell culture. BACKGROUND

[0004] In recent years, advances and applications related to cell culture, a process for growing cells under controlled conditions, have been made. Cell culture vessels or modules containing cells are stored in an incubator, which maintains specific environmental conditions suitable for cell growth. An example application of cell culture includes in vitro fertilization (“IVF”).

[0005] However, cell culture and its applications present technical problems. As an example, certain environmental conditions can be critical to the success of cell culture. Indeed, environmental fluctuations can have a negative impact. Moreover, current cell culture requires hard work from professionals or technicians. This high level of human involvement can cause the environmental conditions within the incubator to change or deviate from favorable environmental conditions. SUMMARY

[0006] In some aspects, the technology described herein relates to a system for cell culture within a chamber, the chamber structurally housing at least a first chamber, a second chamber, and at least a portion of an environmental control subsystem, the system comprising: a first chamber configured to store a plurality of culture dishes containing biological samples; a second chamber adjacent to the first chamber and fluidly isolated from the first chamber by means of one or more first movable structures in a closed configuration, wherein the second chamber is configured to house at least a manipulator assembly for manipulating the plurality of culture dishes; and an environmental control subsystem, wherein the environmental control subsystem controls the respective environments within the first and second chambers, and wherein the environmental control subsystem... The system is configured to: detect a first environmental condition specifying the current temperature, current humidity, and current air composition of a first chamber; detect a second environmental condition specifying the current temperature, current humidity, and current air composition of a second chamber; supply a first airflow to the first chamber via a first airflow pattern determined based on a first cell culture activity performed inside the first chamber to adjust the first environmental condition to a first target environmental condition; and supply a second airflow to the second chamber via a second airflow pattern determined based on a second cell culture activity performed inside the second chamber to adjust the second environmental condition to a second target environmental condition.

[0007] In some respects, the technology described herein relates to a system in which an environmental control subsystem includes a housing that houses at least a portion of an air quality controller, wherein the housing is located outside a casing, and wherein the air quality controller is configured to supply a first airflow and a second airflow.

[0008] In some respects, the technology described herein relates to a system in which an air quality controller includes an air heater, a humidifier, a volatile organic compound (VOC) filter, a high-efficiency particulate air (HEPA) filter, an oxygen absorber, and a carbon dioxide absorber.

[0009] In some respects, the technology described herein relates to a system in which an environmental control subsystem includes a first airflow assembly and a second airflow assembly, wherein: the first airflow assembly supplies a first airflow to a first chamber to adjust a first environmental condition to a first target environmental condition; and the second airflow assembly supplies a second airflow to a second chamber to adjust a second environmental condition to a second target environmental condition.

[0010] In some respects, the technology described herein relates to a system in which a first end of a first airflow assembly is located inside a housing and a second end of the first airflow assembly is located inside a first chamber; and wherein a first end of a second airflow assembly is located inside a housing and a second end of the second airflow assembly is located inside a second chamber.

[0011] In some respects, the technology described herein relates to a system in which an environmental control subsystem includes multiple sensors configured to detect a first environmental condition and a second environmental condition, and wherein the multiple sensors are housed in a housing and include a pressure sensor, a temperature sensor, a humidity sensor and an air composition sensor.

[0012] In some respects, the technology described herein relates to a system in which, when the first airflow mode is a unidirectional airflow mode, supplying the first airflow includes: injecting intake air from an air tank without circulating the air in the first chamber.

[0013] In some aspects, the technology described herein relates to a system in which an environmental control subsystem includes a storage tank, distinct from the air tank, and wherein the environmental control subsystem is further configured to: determine that the current air composition of a first chamber deviates from the air composition specified by a first target environmental condition by more than a predetermined threshold; and in response to determining that the current air composition of the first chamber deviates from the air composition specified by the first target environmental condition, cause the storage tank to inject air into the first chamber to adjust the current air composition of the first chamber to the air composition specified by the first target environmental condition.

[0014] In some respects, the technology described herein relates to a system in which, when the first airflow mode is a closed airflow mode, supplying the first airflow includes: circulating air within the first chamber without injecting air from an air tank.

[0015] In some respects, the technology described herein relates to a system in which, when the first airflow mode is a semi-closed airflow mode, supplying the first airflow includes: circulating air within a first chamber and injecting intake air from an air tank according to a predetermined ratio.

[0016] In some respects, the technology described herein relates to a system in which a first airflow mode is a unidirectional airflow mode and a second airflow mode is a semi-closed airflow mode or a closed airflow mode.

[0017] In some respects, the technology described herein relates to a system in which a first cell culture activity performed inside a first chamber includes culturing unknown cells or cells that are toxic to the environment outside the chamber.

[0018] In some respects, the technology described herein relates to a system in which an environmental control subsystem includes a first heater deployed inside a first chamber, and wherein the environmental control subsystem is further configured to activate the first heater to adjust the current temperature of the first chamber to a temperature specified by a first target environmental condition.

[0019] In some respects, the technology described herein relates to a system in which an environmental control subsystem includes a first air absorber deployed outside a first chamber, and wherein the environmental control subsystem activates the first air absorber based on a first airflow pattern to adjust the current air composition of the first chamber to an air composition specified by a first target environmental condition.

[0020] In some respects, the technology described herein relates to a system in which the temperature specified by a first target environmental condition is between 36.5°C and 37.5°C, the humidity specified by the first target environmental condition is between 38% and 42%, and the air composition specified by the first target environmental condition includes 5%-7% oxygen, 5%-10% carbon dioxide, and 88%-90% nitrogen.

[0021] In some respects, the technology described herein relates to a system in which the total volume of the first chamber and the second chamber is less than 500 liters.

[0022] In some respects, the technology described herein relates to a system in which supplying a first airflow includes filtering intake air from an air tank and / or air inside a first chamber using a volatile organic compound (VOC) filter and a high-efficiency particulate air (HEPA) filter.

[0023] In some respects, the technology described herein relates to a system in which an environmental control subsystem is also configured to determine a first airflow pattern based at least on the size of a first chamber or the remaining capacity of an air tank supplying the first airflow.

[0024] In some respects, the technology described herein relates to a system in which an environmental control subsystem is also configured to determine a second airflow pattern based at least on the dimensions of a second chamber or the remaining capacity of an air tank supplying the second airflow.

[0025] In some respects, the techniques described herein relate to a system in which a biological sample includes one of an oocyte, embryo, egg, sperm, organoid, cell, or tissue.

[0026] In some respects, the technology described herein relates to a system in which: when the first airflow mode is a unidirectional airflow mode, the environmental control subsystem is further configured to control the total air exchange rate (TACH) associated with the first chamber, but not the fresh air exchange rate (FACH) associated with the first chamber; and when the first airflow mode is a semi-closed airflow mode or a closed airflow mode, the environmental control subsystem is further configured to control the TACH associated with the first chamber and the FACH associated with the first chamber.

[0027] In some respects, the technology described herein relates to a system in which an environmental control subsystem is further configured to adjust a first environmental condition to a first target environmental condition using ultraviolet (UV) and / or radiation catalytic ionization (RCI).

[0028] In some respects, the technology described herein relates to a system in which a first target environmental condition is the same as or different from a second target environmental condition.

[0029] In some aspects, the technology described herein relates to a system that further includes an intelligent manipulator subsystem comprising a manipulator component, a camera component, a thermal imager, one or more processors and a non-transitory computer storage medium storing instructions, and an object temperature controller, wherein: the camera component is configured to generate image data; the thermal imager is configured to generate thermal imaging data; one or more processors are configured to execute instructions to generate real-time information associated with one or more objects to be manipulated by the manipulator component based on the image data and the thermal imaging data via a machine learning model; and the object temperature controller is configured to generate one or more thermal control signals based on the thermal imaging data and the real-time information, wherein an environmental control subsystem further supplies a first airflow and a second airflow based on the one or more thermal control signals.

[0030] In some respects, the technology described herein relates to a system in which an environmental control subsystem further supplies a first airflow and a second airflow based on one or more thermal control signals.

[0031] In some respects, the technology described herein relates to a system in which camera components include a vision camera, a microscope camera, and a front-facing microscope camera.

[0032] In some respects, the technology described herein relates to a system in which a visual camera and a thermal imager are mounted on the ceiling of a second chamber, and in which a microscope camera and a microscope front camera are mounted on a manipulator assembly.

[0033] In some respects, the techniques described herein relate to a system in which a machine learning model is configured to extract features associated with one or more objects based on image data and / or thermal imaging data, and to generate real-time information based on those features.

[0034] In some respects, the techniques described in this paper relate to a system in which the machine learning model is one of a support vector machine (SVM), a deep learning model, or a neural network.

[0035] In some aspects, the technology described herein relates to a system further comprising a third chamber configured to perform a cryopreservation or thawing procedure, wherein the third chamber is adjacent to a second chamber and is fluidly isolated from the second chamber by one or more second movable structures based on the second chamber being in a closed configuration, and wherein an environmental control subsystem is further configured to: detect a third environmental condition specifying the current temperature, current humidity, and current air composition of the third chamber; and supply a third airflow to the third chamber via a third airflow pattern determined based on a third cell culture activity performed inside the third chamber to adjust the third environmental condition to a third target environmental condition.

[0036] In some aspects, the technology described herein relates to a method implemented by a microsystem for cell culture, wherein the microsystem includes: a first chamber configured to store a plurality of culture dishes containing biological samples; and a second chamber configured to house at least a manipulator assembly for manipulating the plurality of culture dishes. The method includes: detecting a first environmental condition specifying a current temperature, a current humidity, and a current air composition of the first chamber; detecting a second environmental condition specifying a current temperature, a current humidity, and a current air composition of the second chamber; supplying a first airflow to the first chamber via a first airflow pattern determined based on a first cell culture activity performed inside the first chamber to adjust the first environmental condition to a first target environmental condition; and supplying a second airflow to the second chamber via a second airflow pattern determined based on a second cell culture activity performed inside the second chamber to adjust the second environmental condition to a second target environmental condition.

[0037] In some respects, the technology described herein relates to a method in which, when the first airflow mode is a unidirectional airflow mode, supplying the first airflow includes: injecting intake air from an air tank without circulating the air in the first chamber.

[0038] In some respects, the technology described herein relates to a method in which, when the first airflow mode is a closed airflow mode, supplying the first airflow includes: circulating air within the first chamber without injecting air from an air tank.

[0039] In some respects, the technology described herein relates to a method in which, when the first airflow mode is a semi-closed airflow mode, supplying the first airflow includes: circulating air within a first chamber and injecting intake air from an air tank according to a predetermined ratio.

[0040] In some respects, the technology described herein relates to a method in which a first airflow pattern is a unidirectional airflow pattern and a second airflow pattern is a semi-closed airflow pattern or a closed airflow pattern.

[0041] In some respects, the techniques described herein relate to a method in which a first target environmental condition is the same as or different from a second target environmental condition.

[0042] In some respects, the technology described herein relates to a method in which the temperature specified by a first target environmental condition is between 36.5°C and 37.5°C, the humidity specified by the first target environmental condition is between 38% and 42%, and the air composition specified by the first target environmental condition includes 5%-7% oxygen, 5%-10% carbon dioxide, and 88%-90% nitrogen.

[0043] In some respects, the technology described herein relates to a method in which the total volume of the first chamber and the second chamber is less than 500 liters.

[0044] In some respects, the technology described herein relates to a method in which supplying a first airflow includes filtering intake air from an air tank and / or air inside a first chamber using a volatile organic compound (VOC) filter and a high-efficiency particulate air (HEPA) filter.

[0045] In some respects, the techniques described herein relate to a method in which a biological sample includes one of an oocyte, embryo, egg, sperm, organoid, cell, or tissue.

[0046] In some aspects, the technology described herein relates to a system for cell culture within a chamber, the chamber being structurally housed at least a first chamber, a second chamber, and at least a portion of an environmental control subsystem, the system comprising: a first chamber configured to store a plurality of culture dishes containing biological samples; a second chamber adjacent to the first chamber and fluidly isolated from the first chamber by one or more first movable structures based on a closed configuration of one or more first movable structures, wherein the second chamber is configured to house at least a manipulator assembly for manipulating the plurality of culture dishes; and an environmental control subsystem configured to: detect a first environmental condition specifying the current temperature, current humidity, and current air composition of the first chamber; detect a second environmental condition specifying a second The current temperature of the first chamber, the current humidity of the second chamber, and the current air composition of the second chamber; supplying a first airflow to the first chamber via a first airflow mode to adjust the first environmental conditions to a first target environmental condition; and supplying a second airflow to the second chamber via a second airflow mode to adjust the second environmental conditions to a second target environmental condition, wherein: when the first airflow mode is a unidirectional airflow mode, supplying the first airflow includes: injecting air from an air tank without circulating the air inside the first chamber; when the first airflow mode is a closed airflow mode, supplying the first airflow includes: circulating the air inside the first chamber without injecting air from an air tank; when the first airflow mode is a semi-closed airflow mode, supplying the first airflow includes: circulating the air inside the first chamber and injecting air from an air tank according to a predetermined ratio.

[0047] In some respects, the technology described herein relates to a system in which an environmental control subsystem is further configured to: determine a first airflow pattern based on a first cell culture activity performed inside a first chamber; and determine a second airflow pattern based on a second cell culture activity performed inside a second chamber.

[0048] In some respects, the technology described herein relates to a system in which a first cell culture activity involves culturing unknown cells or cells that are toxic to the environment outside the chamber.

[0049] In some respects, the techniques described herein relate to a system in which a second cell culture activity involves manipulating oocytes, embryos, eggs, or sperm. Attached Figure Description

[0050] Figure 1 This is a block diagram of an example automated incubator system according to some embodiments of the present disclosure, the system including different chambers, an environmental control subsystem and an intelligent manipulator subsystem.

[0051] Figure 2A , Figure 2B , Figure 2C ,Figure 2D and Figure 2E The figures illustrate some embodiments according to the present disclosure. Figure 1 Different views of an example automated incubator system.

[0052] Figure 2F An example perspective view of an automated incubator system according to some embodiments of the present disclosure is illustrated.

[0053] Figure 3A According to some embodiments of this disclosure Figure 1 Block diagram of the environmental control subsystem.

[0054] Figure 3B The illustrations depict some embodiments according to this disclosure. Figure 3A A block diagram of a part of the environmental control subsystem.

[0055] Figure 4 The illustrations depict some embodiments according to this disclosure. Figure 1 A block diagram of an intelligent controller system.

[0056] Figure 5A The figures illustrate some embodiments according to the present disclosure. Figure 1 An enlarged perspective view of an example of a part of an intelligent manipulator system.

[0057] Figure 5B The figures illustrate some embodiments according to the present disclosure. Figure 5A An enlarged representation of a portion of the example perspective.

[0058] Figure 6A It is for control according to some embodiments of this disclosure Figure 1 The flowchart shows the environmental conditions in an example automated incubator system.

[0059] Figure 6B It is for control according to some embodiments of this disclosure Figure 1 The flowchart illustrates an example process for air quality in an example automated incubator system.

[0060] Figures 7A-7B This is a flowchart of an example process for controlling a manipulator component to manipulate a biological sample, according to some embodiments of the present disclosure.

[0061] Figure 8 An example user interface according to some embodiments of the present disclosure is illustrated, through which an example automated incubator system can be monitored.

[0062] Figure 9 The illustration shows the overall architecture of an example automated incubator system according to some embodiments of the present disclosure. Detailed Implementation

[0063] This specification describes apparatus and techniques for controlling cell culture environmental conditions (e.g., environmental conditions) to improve the success rate of cell cultures, such as in vitro fertilization (IVF) cell cultures. As will be described, the system can utilize various environmental control mechanisms, sensing technologies, and / or automation technologies to control and maintain environmental conditions in one or more chambers of the system to target conditions. Target conditions can specify a particular combination of temperature, humidity, air pressure, and / or air composition. In some embodiments, the system can utilize airflow control mechanisms (e.g., allowing air to flow into the chamber) in combination with non-airflow control mechanisms (e.g., heating the surfaces inside the chamber). For example, these mechanisms can be used to effectively maintain or restore environmental conditions in (multiple) chambers to target conditions within a threshold time period. In this example, environmental conditions can be maintained in response to the detection of fluctuations in environmental conditions. Additionally, the system can apply different airflow control mechanisms (e.g., with or without circulating air) to the individual chambers associated with cell culture to control the conditions in the respective chambers.

[0064] In some embodiments, the system can utilize a vision camera, optionally combined with a thermal imager, to perform automated actions on cells in a culture dish. For example, the system can control manipulator components (e.g., a robotic arm) to manipulate the cells. Regarding the thermal imager, in some embodiments, the system can use thermal imaging data to control the temperature at specific locations within the system. In contrast, prior art relies heavily on manual cell culture, which cannot accurately maintain the environmental conditions within the chambers associated with cell culture, potentially reducing the chances of successful culture.

[0065] Typically, cell culture involves significant human input throughout the various stages of culture. In the context of IVF, example stages can include the progression from oocyte retrieval to fertilization and embryo culture. During these stages, substantial human intervention and manual manipulation are usually involved. For instance, an embryologist operating a manipulation system may manipulate oocytes, such as removing them for clinical intracytoplasmic sperm injection (ICSI) and storing them in a culture incubator chamber. A major challenge in successfully performing cell culture is accurately maintaining the environmental conditions within the culture incubator chamber, such as the temperature and air composition suitable for or optimized for culture. For example, IVF performed around the culture incubator chamber by an embryologist or other personnel can cause fluctuations in the environmental conditions within the chamber. Similarly, transporting biological samples (such as oocytes, embryos, etc.) from the culture incubator chamber to a work area for manipulation can lead to fluctuations in the environmental conditions associated with the biological samples. In both examples, environmental conditions may not be accurately maintained and may deviate from the optimal conditions for cell culture.

[0066] More specifically, the temperature, humidity, and / or air composition within the culture chamber can change as embryologists enter or leave the work area or manipulation area of ​​the operating workstation due to variations in environmental conditions both inside and outside the culture chamber. As is known to those skilled in the art, changes in environmental conditions can negatively impact cell culture outcomes (e.g., hindering healthy embryo growth). While limiting the presence of personnel (e.g., by reducing the time professionals spend near the culture chamber) can better control environmental conditions, this can lead to increased human error, as manipulation within a significantly limited timeframe results in increased stress. Human error can lead to reduced cell culture success rates or adverse consequences, such as impaired oocyte viability. Adverse consequences, for example, can include reduced blastocyst formation, increased chromosomal abnormalities or fragmentation, decreased implantation rates, abnormal epigenetic patterns, and increased miscarriage rates, among others.

[0067] Furthermore, even without human intervention, environmental conditions within the culture chamber can fluctuate. For example, environmental conditions may change due to air consumed or released by cells during growth. Environmental conditions may also change due to the input, output, or exchange of biological samples between the culture chamber and external areas. As has been demonstrated, these changes in environmental conditions within the culture chamber can adversely affect the success of cell culture. For instance, when the air composition changes due to cell growth (e.g., an increase or decrease in carbon dioxide levels), the pH in the culture dish may deviate from a level suitable for cell culture, leading to unsatisfactory cell culture results.

[0068] Furthermore, ideal or optimized conditions for cell culture can vary throughout the various stages of culture. For example, in the context of in vitro fertilization (IVF) or IVM (in vitro maturation), the desired percentage of oxygen in the air surrounding the oocyte or early embryo may differ as the oocyte matures or the embryo develops. More specifically, the average oxygen consumption of seemingly healthy oocytes measured after three days of culture may differ from that measured after eight days. For embryonic development, different stages of embryos may have different oxygen consumption due to variations in their ability to be associated with anaerobic and aerobic metabolism. More specifically, the average oxygen consumption of two-cell embryos may vary at the blastocyst stage and after more than five days of culture in humans. Moreover, the variation in average oxygen consumption may be even greater for non-human embryos compared to human embryos. Thus, strictly fixed environmental conditions can lead to poor cell culture results.

[0069] To address at least some of the aforementioned problems, the system described herein (generally referred to herein as the "automated incubator system" or simply the "system") can utilize innovative automation technologies within an integrated incubator unit or system. As will be described, environmental control mechanisms (e.g., air quality and temperature control) can be used. In some embodiments, machine learning techniques can be used to accurately and adaptively control environmental conditions. The system can also automatically manipulate cell culture dishes containing biological samples (e.g., tissues, oocytes, embryos, etc.) without human intervention or with only limited human intervention.

[0070] The system may include a microchamber where environmental conditions can be maintained at target conditions via airflow control and non-airflow control mechanisms. In some embodiments, the airflow control mechanism may include at least controlling air quality to a desired quality (e.g., desired temperature, humidity, pressure, and / or composition) by filtering recirculated air. In other embodiments, the airflow control mechanism may include at least supplying intake air (e.g., air stored in an air canister and not yet circulated) to a specific chamber using airflow components (e.g., valves and ducts). Non-airflow control mechanisms may include heating specific surfaces within the chamber using a heater and / or absorbing excess oxygen, carbon dioxide, nitrogen oxides, or other air components from the chamber using an air absorber.

[0071] In some embodiments, the system may include a manipulation chamber, an incubator culture chamber, an inlet chamber, an outlet chamber, and an auxiliary chamber. The manipulation chamber may be used to house components for manipulating biological samples (e.g., a robotic arm, a vision camera, etc.). The incubator culture chamber may store cell culture vessels or modules containing biological samples for cell culture. The inlet chamber may include one or more inlet compartments that may be used to receive biological samples into the system before transporting them to the manipulation chamber and / or the incubator culture chamber. The outlet chamber may be used to house a transport capsule containing the biological samples for transporting them to the external environment. The auxiliary chamber may be used for various purposes, such as cryopreservation. In some examples, the manipulation chamber, incubator culture chamber, inlet chamber, outlet chamber, and auxiliary chamber may be structurally (e.g., separated by walls, sliding doors, etc.) and / or fluidly (e.g., air from one chamber may not readily flow to another). This allows the system to flexibly and individually control the environmental conditions within each chamber (e.g., based on specific cell culture activities or operations performed in the respective chamber). Furthermore, by deploying the individual chambers within a single space that provides isolation from the external environment (e.g., within a housing), the system advantageously allows all cell culture-related operations to be performed automatically within the housing, avoiding fluctuations in environmental conditions during the handling and transport of culture vessels. In some examples, the system may also include a housing located outside the manipulation chamber, incubator culture chamber, inlet chamber, outlet chamber, and auxiliary chambers. The housing may house at least air quality control equipment (e.g., air absorbers, air filters, etc.), which can be used to manage the environmental conditions within each chamber.

[0072] Advantageously, through coordination between airflow and non-airflow control mechanisms, the system can more effectively maintain air quality within threshold time periods (e.g., 1 second, 5 seconds, 10 seconds, etc.). Depending on the type of application and the stage of cell culture (e.g., determined by the system or identified by the user), the system can adjust target conditions to provide an improved cell culture environment.

[0073] Furthermore, the system can employ different airflow control mechanisms for each chamber. For example, the system can utilize a unidirectional airflow mode to supply air to the incubator culture chamber. In unidirectional airflow mode, the air in the incubator culture chamber may not circulate periodically. Instead, the system can periodically supply intake air stored in an air tank to the incubator culture chamber via an air pipe, while allowing previously supplied air to flow out of the incubator culture chamber. Simultaneously, the system can utilize semi-closed or closed airflow modes to supply air to any of the manipulation chamber, incubator culture chamber, inlet chamber, outlet chamber, and auxiliary chambers. For example, the system can utilize a semi-closed or closed airflow mode to supply air to the manipulation chamber, in which the manipulator assembly can autonomously manipulate cells. In some embodiments, the manipulator assembly can acquire (e.g., grasp or otherwise transfer) cells from the culture chamber to the manipulation chamber. In closed airflow mode, the system can circulate the air within the manipulation chamber without injecting any intake air. In semi-closed airflow mode, the system can replenish the air in the manipulation chamber with newly supplied air.

[0074] In some embodiments, the system can determine which airflow pattern is suitable for each chamber. For example, the system can select the airflow pattern based on information including the chamber size, the type of cell culture being performed, the remaining air intake capacity inside the air tank, and so on. The system can respond to changes in environmental conditions in different or more appropriate ways depending on which airflow pattern is selected. For example, and for a unidirectional airflow pattern, the system can detect that the oxygen level (e.g., 8%) in the air inside the incubator culture chamber is higher than a desired level (e.g., 5%). In this example, the system can inject air with a lower oxygen content. As another example, based on the selection of a semi-closed or closed airflow pattern, the system can trigger the activation of an oxygen absorber to reduce the oxygen in the air, thereby regulating the air composition, for example, within the incubator culture chamber.

[0075] In some embodiments, when changes in air composition exceed a certain level, the system may employ a specific mechanism that can adjust the air composition more quickly than recirculating and filtering existing air. For example, when the nitrogen level increases by at least a threshold percentage (e.g., due to the presence of liquid nitrogen in the chamber), the system may flush air stored in a reservoir associated with the chamber to immediately flow into the chamber and reduce the nitrogen level. Flushing air from the reservoir into the chamber can advantageously allow the nitrogen level to recover to the desired level (e.g., 89%) more quickly than recirculating, filtering, and flowing air through air pipes.

[0076] As described above, both airflow and non-airflow control mechanisms can utilize thermal imaging data. For example, when thermal imaging data indicates that the temperature of an object (e.g., liquid in a pipette) deviates from a desired temperature, the system can use an airflow control mechanism to direct hotter or colder air toward the object. As another example, when thermal imaging data indicates that the temperature inside an object (e.g., a petri dish) deviates from a desired temperature, the system can use a non-airflow control mechanism to regulate its temperature. In this example, the system can activate a heater or cooling device near the object. Advantageously, thermal imaging data provides actionable insights into the temperature at any location within the system.

[0077] The system can also control the included manipulator components to manipulate biological samples. More specifically, the system can use machine learning techniques to control the manipulator components, which can optionally combine thermal imaging data to analyze image data. In this way, the system can obtain real-time information about the object to be manipulated (e.g., identity, location, temperature, etc.) and manipulate the object based on this real-time information. In some examples, the system can utilize computer vision techniques to process image data and optionally process thermal imaging data to derive or extract features associated with the object (e.g., shape features). The extracted object features can then be used to train a machine learning model or to perform inference using the machine learning model. The training process may include training the machine learning model using at least a subset of the derived features. The trained machine learning model can then be used to generate information about the object, thereby generating motion control signals to control the operation of the manipulator components, thus enabling manipulation of the biological sample without human intervention.

[0078] Additionally and / or optionally, the system can use image sequences capturing how professionals (e.g., embryologists) manipulate biological samples using different culture tools to train a machine learning model for controlling the manipulator components. In this way, the manipulator components can manipulate the biological samples in a manner consistent with that performed by a professional. Automated operation reduces variations in environmental conditions due to the presence of humans. Unmanned operation not only avoids human error that can result from working under time pressure but also allows for system miniaturization, thereby reducing the resources required to control environmental conditions within the chamber (e.g., the supplied gas flow rate). Advantageously, by integrating real-time image capture technology and automated manipulator components (e.g., robotic arms, cell pickers, etc.), the system can be remotely controlled by professionals (e.g., for ICSI, laser, or biopsy) to avoid human interference with the culture environment.

[0079] The foregoing aspects and numerous advantages of this disclosure will become more readily apparent from the accompanying drawings and from the following description.

[0080] Example System Block Diagram

[0081] Figure 1 This is a block diagram of an automated incubator system 100 according to some embodiments of the present disclosure. The system includes an incubator culture chamber 130, a control chamber 120, an inlet chamber 140, an outlet chamber 150, an auxiliary chamber 160, an environmental control subsystem 102, and an intelligent manipulator subsystem 104. (As shown...) Figure 1 As illustrated, the automated incubator system 100 receives a biological sample 110 from the external environment via an inlet chamber 140. The automated incubator system 100 transports the biological sample 110 to the external environment via an outlet chamber 150. An intelligent manipulator subsystem 104 can manipulate the biological sample 110 within the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160. An environmental control subsystem 102 can control the environmental conditions within the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160 to culture the biological sample 110. Examples of biological samples 110 include human cells, non-human cells, tissues, bacterial cells, stem cells, primary cells, mammalian oocytes (e.g., human oocytes), eggs, embryos, sperm, organoids, and the like. In some embodiments, each of the manipulation chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and the auxiliary chamber 160 may be structurally (e.g., separated by walls, doors, or other movable physical structures) and / or fluidly (e.g., air from one chamber may not readily flow to another).

[0082] The oral cavity chamber 140 may include one or more entrance compartments that can be used to receive biological samples 110 into the automated incubator system 100. For example, the oral cavity chamber 140 may include a transfer compartment and an inner compartment, which may be separated by a sliding door. The transfer compartment may serve as an intermediate space where the vessel containing the biological sample 110 is cleaned or sterilized before entering the inner compartment, and / or equilibrated with the conditions of the inner compartment before the sliding door is opened. In some embodiments, the oral cavity chamber 140 may meet the requirements of ISO Class 7 and / or Class 8 cleanrooms. For example, the transfer compartment may meet the requirements of ISO Class 8 cleanrooms, while the inner compartment may meet the requirements of ISO Class 7 cleanrooms.

[0083] The exit chamber 150 can be used to house a transport compartment containing the biological sample 110. Additionally, the exit chamber 150 can be used to transport materials to be placed outside the automated incubator system 100. In some embodiments, the inlet chamber 140 can meet the requirements of an ISO Class 7 or 8 cleanroom. A sliding door can be installed between the exit chamber 150 and the manipulation chamber 120.Figure 1 (Not shown in the diagram), such as a movable baffle. In some embodiments, when the culture dish is to be transported through the outlet chamber 150 to the outside of the automated incubator system 100, the environmental control subsystem 102 may use a unidirectional airflow pattern to balance the environmental conditions within the outlet chamber 150 and the manipulator chamber 120. After the environmental conditions within the outlet chamber 150 and the manipulator chamber 120 are balanced (e.g., at least substantially the same), the culture dish can be transported through the manipulator chamber 120 to the outlet chamber 150.

[0084] The auxiliary chamber 160 can be used for a variety of purposes. For example, in the context of IVF, the auxiliary chamber 160 can be used as a space for cryopreservation. The auxiliary chamber 160 can house an immersion chamber filled with liquid nitrogen for cryopreservation or other applications. In some embodiments, the auxiliary chamber 160 can meet the requirements of an International Organization for Standardization (ISO) Class 7 or 8 cleanroom. A sliding door can be installed between the auxiliary chamber 160 and the operating chamber 120. Figure 1 (Not shown in the image).

[0085] The incubator culture chamber 130 can store cell culture dishes or modules containing biological samples 110 for cell culture. As noted above, the environmental conditions within the incubator culture chamber 130 can be controlled by the environmental control subsystem 102 to maintain target conditions suitable for cell culture, such as temperature and air composition. In some embodiments, the incubator culture chamber 130 can meet the requirements of International Organization for Standardization (ISO) Class 6 or Federal Standard 209 1000.

[0086] The manipulation chamber 120 can be used to house at least a portion of the intelligent manipulator subsystem 104 for manipulating the biological sample 110. For example, the manipulator assembly of the intelligent manipulator subsystem 104 ( Figure 1 (Not shown) The biological sample 110 inside the manipulation chamber 120 can be manipulated. In some embodiments, the manipulation chamber 120 may meet the requirements of International Organization for Standardization (ISO) Level 6 or Federal Standard 209 1000.

[0087] The intelligent manipulator subsystem 104 may include a combination of hardware, firmware, and software components and can be configured to automatically process biological samples 110 for culture without the assistance of human professionals. As noted above, the intelligent manipulator subsystem 104 can manipulate (e.g., access, hold, place, transfer, move, process, etc.) the biological samples 110 within the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160. In some embodiments, the intelligent manipulator subsystem 104 may utilize visual cameras of different resolutions and thermal imagers to identify objects of interest for controlling manipulator components (e.g., robotic arms) to automatically manipulate cells in culture dishes. The intelligent manipulator subsystem 104 may also use thermal imaging data from the thermal imager and information about the identified objects to generate thermal control signals for controlling the temperature at specific locations within the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160.

[0088] In some embodiments, the intelligent manipulator subsystem 104 may utilize machine learning techniques to analyze image data from a vision camera and thermal imaging data from a thermal imager to identify real-time information (e.g., identity, location, temperature, etc.) of objects (e.g., biological samples in a culture dish, pipette tips, wells in a culture dish, etc.) inside the manipulation chamber 120. The intelligent manipulator subsystem 104 may utilize computer vision techniques to process the image and thermal imaging data to derive or extract features (e.g., shape features) associated with the object being or to be manipulated by the manipulator component.

[0089] The environmental control subsystem 102 may include a combination of airflow and non-airflow control hardware, firmware, and software components, and may be configured to control and maintain environmental conditions in the manipulation chamber 120, incubator culture chamber 130, inlet oral cavity chamber 140, outlet oral cavity chamber 150, and / or auxiliary chamber 160 at target conditions. Target conditions may specify a particular combination of temperature, humidity, air pressure, and / or air composition. It should be noted that some parts of the environmental control subsystem 102 may be distributed within the manipulation chamber 120, incubator culture chamber 130, inlet oral cavity chamber 140, outlet oral cavity chamber 150, and / or auxiliary chamber 160, while other parts of the environmental control subsystem 102 may be deployed outside any of the aforementioned chambers.

[0090] In some embodiments, the environmental control subsystem 102 may combine airflow control mechanisms (e.g., generating and flowing a specific mass of air into a chamber) with non-airflow control mechanisms (e.g., heating or cooling surfaces or points within the chamber) to effectively maintain or restore environmental conditions in the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160 to target conditions. In some embodiments, the environmental control subsystem 102 may use airflow control mechanisms to control air quality to a desired quality (e.g., desired temperature, humidity, pressure, and / or air composition). Airflow control mechanisms may include filtering recirculated air and / or supplying intake air (e.g., air stored in an air tank and not recirculated) to the manipulation chamber 120 or incubator culture chamber 130. The environmental control subsystem 102 may also utilize non-airflow control mechanisms to control environmental conditions. Non-airflow control mechanisms may include using a heater to heat specific surfaces within the manipulation chamber 120, or using an air absorber to absorb excess oxygen, carbon dioxide, nitrogen oxides, or other air components from the incubator culture chamber 130 or the manipulation chamber 120.

[0091] Furthermore, the environmental control subsystem 102 can apply different airflow control mechanisms to the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160 to control the environmental conditions in the respective chambers. For example, the environmental control subsystem 102 can supply air to the incubator culture chamber 130 using a unidirectional airflow mode. Simultaneously, the environmental control subsystem 102 can supply air to the manipulation chamber 120 using a semi-closed or closed airflow mode, where the manipulator assembly can automatically manipulate cells in cell culture instruments (e.g., culture dishes, vessels, pipettes, containers, etc.). Furthermore, the environmental control subsystem 102 can determine which airflow control mode (e.g., unidirectional, semi-closed, or closed airflow) is suitable for the corresponding chamber based on various factors (such as chamber size, type of cell culture being performed, remaining air intake capacity inside the air tank, etc.). In some embodiments, the system can respond to user input indicating the selection of each mode. For example, the system can respond to wireless or wired communication from an application presenting a user interface. In some embodiments, the system may include a display that enables the selection of a mode.

[0092] In some embodiments, the environmental control subsystem 102 can adjust target conditions within the incubator culture chamber 130 or manipulation chamber 120 based on the type of application and / or the stage of cell culture (e.g., cell culture activity). For example, when performing IVF treatment using the incubator culture chamber 130, the environmental control subsystem 102 can set the target conditions in the incubator culture chamber 130 to: a temperature of approximately 37°C, a humidity of 40%, and an air composition of 5% to 6% oxygen, 5% to 6% carbon dioxide, and 88% to 90% nitrogen. In some examples, target conditions may include temperatures of 35°C, 35.2°C, 35.4°C, 35.6°C, 35.8°C, 36°C, 36.2°C, 36.4°C, 36.6°C, 36.8°C, 37°C, 37.2°C, 37.4°C, 37.6°C, 37.8°C, 38°C, 38.2°C, 38.4°C, 38.6°C, 38.8°C, 39°C, or any range thereof; humidity of 36%, 36.5%, 37%, 37.5%, 38%, 38.5%, 39%, 40%, 40.5%, 41%, 41.5%, 42%, 42.5%, 43%, 43.5%, 44%, or any range thereof; and air composition of 5% to 7% oxygen, 5% to 7% carbon dioxide, and 88% to 90% nitrogen. Additionally and / or optionally, the environmental control subsystem 102 can further fine-tune the target conditions at various stages of the incubation period. For example, the environmental control subsystem 102 can vary the carbon dioxide level between 5% and 10% at various stages of IVF treatment (e.g., 5-day incubation period, 10-day incubation period, several days post-fertilization, etc.). The environmental control subsystem 102 can also adjust the carbon dioxide level based on the external environment in which the automated incubator system 100 is located. More specifically, when the automated incubator system 100 is located in a low-pressure environment (e.g., at high altitudes on Earth, in aerospace, etc.), the environmental control subsystem 102 can increase the carbon dioxide level from 5% to 10%. For example, when the automated incubator system 100 is at a certain altitude (e.g., above 3000 meters), the environmental control subsystem 102 can raise the carbon dioxide level to about, at least or at least about 6%, 6.2%, 6.4%, 6.6%, 6.8%, 7.0%, 7.2%, 7.4%, 7.6%, 7.8%, 8.0%, 8.2%, 8.4%, 8.6%, 8.8%, 9.0%, or any value between these ranges. Advantageously, the elevated carbon dioxide level can help maintain the pH value in the culture dishes at a desired level. As another example, when the automated incubator system 100 is located in an environment with high atmospheric pressure (e.g., sea level), the environmental control subsystem 102 can adjust the carbon dioxide level to about 5%, 5.2%, 5.4%, 5.6%, 5.8%, 6.0%, 6.2%, 6.4%, 6.6%, or any value between these ranges.

[0093] Example System Perspective

[0094] Figure 2A , Figure 2B , Figure 2C and Figure 2D The figures illustrate some embodiments according to the present disclosure. Figure 1 Example view of an automated incubator system 100. Figure 2A An example perspective view of an automated incubator system 100 is shown, in which certain portions of the intelligent manipulator subsystem 104 and the environmental control subsystem 102 have been removed, and some parts have been disassembled. Figure 2A As illustrated, the automated incubator system 100 includes a housing 230 (e.g., a cell culture chamber) that structurally houses an incubator culture chamber 130, a manipulation chamber 120, an inlet chamber 140, an outlet chamber 150, and an auxiliary chamber 160. In some embodiments, the housing 230 may be made of a variety of materials, including insulating materials. For example, the housing 230 may be made of materials that provide robust structural support (e.g., stainless steel, aluminum, powder-coated steel, anodized aluminum, etc.) and materials that provide thermal and / or airtight insulation (e.g., fiberglass, polyurethane foam, vacuum insulation panels, etc.). Additionally, the space within the housing 230 may be or nearly airtight. By deploying the manipulation chamber 120, the incubator culture chamber 130, the inlet chamber 140, the outlet chamber 150, and the auxiliary chamber 160 within the housing 230, the automated incubator system 100 can be highly integrated, thereby advantageously allowing all different cell culture-related operations to be performed automatically within the housing 230. Compared to other systems where the manipulation chamber and incubator chamber are not integrated within a physical structure isolated from the external environment (e.g., within enclosure 230), the automated incubator system 100 also avoids fluctuations in environmental conditions during the transport of biological samples. For example, as will be described, the environmental control subsystem 102 can maintain and / or regulate the environmental conditions within the manipulation chamber 120 and the incubator chamber 130 to make them identical (e.g., the same temperature, the same humidity, the same air composition, the same pressure, etc.) when transporting biological samples between the manipulation chamber 120 and the incubator chamber 130.

[0095] exist Figure 2A In the environmental control subsystem 102, the housing 220 houses one or more air absorbers 352 and at least a portion of the air quality controller 320 (e.g., Figure 2B The quality control engine 322 and air filter 330 shown) and one or more air analyzers 310A-310N (will be referenced) Figure 3A and Figure 3B (Describe it). For example... Figure 2AAs illustrated, the incubator culture chamber 130 includes one or more modules 210A-210N, each of which can contain a biological sample. Although Figure 2A The housing 220 is shown to be located outside the enclosure 230, but it should be noted that in other embodiments, the housing 220 and / or the environmental control subsystem 102 may be deployed entirely inside the enclosure 230.

[0096] In some embodiments, the total capacity (e.g., the capacity or volume of the housing 230) of the control chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160 can be between 30 liters (L) and 500 L. In some embodiments, the total capacity of the automated incubator system 100 can be approximately or less than 30 L, 80 L, 130 L, 180 L, 230 L, 280 L, 330 L, 380 L, 430 L, 480 L, 530 L, or any value range therebetween. For example, except for the housing 220 accommodating the air quality controller 320, one or more air absorbers 352, and one or more air analyzers 310A-310N, the automated incubator system 100 can be rectangular in shape, having a length of approximately 60 cm, a width of approximately 35 cm, and a height of approximately 35 cm. A significant portion of the space in the automated incubator system 100 can be occupied by the control chamber 120 and the incubator culture chamber 130. As noted above, the incubator culture chamber 130 may include multiple modules 210A-210N, which can accommodate different biological samples.

[0097] like Figure 2A As illustrated, some parts of the environmental control subsystem 102 may be deployed outside the operating chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and the auxiliary chamber 160. For example, portions of the air quality controller 320 (e.g., the quality control engine 322) and one or more air analyzers 310A-310N are shown housed in a housing 220, which is deployed outside and adjacent to the operating chamber 120. Other parts of the environmental control subsystem 102 (e.g., the air tank 326, the air heater 328, and the airflow assemblies 340A-340N) may be deployed inside the operating chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and / or the auxiliary chamber 160.

[0098] Figure 2B The diagram shows Figure 1 An example perspective view of an automated incubator system 100, in which certain parts (e.g., chamber 230) have been removed. Figure 2BAs illustrated, the environmental control subsystem 102 includes airflow assembly 340A, airflow assembly 340B, airflow assembly 340C, sensor 356, and heater 354. Airflow assembly 340A can guide airflow between the housing 220 and the incubator culture chamber 130. For example, air generated by the air quality controller 320 can flow from airflow assembly 340A to the incubator culture chamber 130. As another example, excess oxygen, carbon dioxide, and / or nitrogen inside the incubator culture chamber 130 can be directed to the air absorber 352 and absorbed by airflow assembly 340A. Airflow assembly 340B can guide airflow between the housing 220 and the inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160. Airflow assembly 340C can guide airflow between the housing 220 and the control chamber 120.

[0099] exist Figure 2B In this embodiment, the manipulation chamber 120 is shown to include one or more modules 240A-240N located on a worktable 460. Each of the modules 240A-240N can accommodate a different biological sample. Each of the modules 240A-240N can accommodate a heater 354 and a sensor 356, which can be used to sense and regulate the temperature associated with the one or more modules 240A-240N.

[0100] like Figure 2B As illustrated, one end of airflow assembly 340A can be connected to air quality controller 320 and / or one or more air analyzers 310A-310N, and the other end can extend into incubator chamber 130. One end of airflow assembly 340B can be connected to air quality controller 320, and the other end can extend into inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160. One end of airflow assembly 340C can be connected to air quality controller 320, and the other end can extend into control chamber 120.

[0101] More specifically, in some embodiments, each of airflow assembly 340A, airflow assembly 340B, and airflow assembly 340C may include an air valve and an air pipe, which the environmental control subsystem 102 may utilize through an airflow control mechanism to maintain environmental conditions in the respective chambers. For example, airflow assembly 340A may include at least two air pipes that are substantially parallel to each other. One or more of airflow assemblies 340A may be used to direct air or other gases inside the incubator culture chamber 130 to an air analyzer 310A and an air quality controller 320 for analysis of air quality (e.g., temperature, humidity, composition, and / or pressure). Other air pipes of airflow assembly 340A may be used to direct air processed (e.g., filtered, circulated, etc.) by the air quality controller 320 based on the analysis of the air analyzer 310A into the incubator culture chamber 130. The environmental control subsystem 102 may similarly utilize airflow assembly 340B to direct air for sampling and analysis, and utilize airflow assembly 340C to direct air for sampling and analysis.

[0102] like Figure 2B As shown, sensor 356 and heater 354 can be deployed in different parts of the incubator chamber 130. For example, each sensor 356 and each heater 354 can be deployed inside each module 210A-210N to sense the temperature within each module for temperature regulation. Although Figure 2B The illustration shows sensors 356 and heaters 354 deployed within various portions of the incubator culture chamber 130 and the manipulation chamber 120. However, it should be noted that sensors 356 and heaters 354 can also be deployed at any other point within the automated incubator system 100 (e.g., certain locations on the workbench 460) or other chambers. In some embodiments, each sensor 356 may be paired with each heater 354 for detecting and heating the temperature associated with a specific point within the automated incubator system 100. It should be noted that each heater 354 may also be embodied as a temperature regulating device capable of both raising and lowering the temperature. Components of the environmental control subsystem 102 will be... Figure 3A and Figure 3B The details are described in further detail.

[0103] Figure 2C The illustration shows an example perspective view of a defined portion of an automated incubator system 100. (See diagram below.) Figure 2CAs illustrated, some of the sensors 356 and heaters 354 of the environmental control subsystem 102 are deployed on the workbench 460. Furthermore, the oral cavity chamber 140 may include a transfer compartment 140-1 and an inner compartment 140-2. The transfer compartment 140-1 and the inner compartment 140-2 may be separated by a sliding door 140-3. As noted above, the transfer compartment 140-1 may serve as an intermediate space in which the vessel containing the biological sample 110 is cleaned or sterilized before entering the inner compartment 140-2, and / or equilibrated with the conditions of the inner compartment 140-2 before the sliding door 140-3 is opened. In some embodiments, the biological sample within the culture vessel may be received by the transfer compartment 140-1. Inside the transfer compartment 140-1, the culture vessel may be air-sprayed using a unidirectional airflow pattern implemented by the environmental control subsystem 102 (e.g., for cleaning or sterilization purposes). Subsequently, the air-sprayed culture vessels can be transported to the inner compartment 140-2. Before transporting the culture vessels to the control chamber 120 and / or the incubator culture chamber 130, the environmental control subsystem 102 can use a unidirectional airflow mode or other airflow modes (e.g., a semi-closed or closed airflow mode) to balance the environmental conditions within the inner compartment 140-2 and the control chamber 120.

[0104] Advantageously, by balancing or equalizing the environmental conditions within the inlet chamber 140, manipulation chamber 120, incubator chamber 130, and / or auxiliary chamber 160 before transporting culture vessels (e.g., one or more modules 210A-210N containing biological samples), the automated incubator system 100 can meet more stringent cleanroom requirements. More specifically, compared to systems where isolation from the external environment is inadequate or environmental conditions are uneven or unbalanced during biological sample transport, the automated incubator system 100 can more accurately maintain the environmental conditions within the chamber 230 at the desired or optimal conditions for a specific cell culture activity. Through the coordination of the various components of the automated incubator system 100 (e.g., transfer compartment 140-1, internal compartment 140-2, airflow components 340A-340N, heater 354, air absorber 352, etc.), the automated incubator system 100 can also enable the operating chamber 120, incubator culture chamber 130, inlet oral cavity chamber 140, outlet oral cavity chamber 150 and / or auxiliary chamber 160 to meet the higher cleanroom requirements of ISO Class 7, ISO Class 6 and / or ISO Class 5.

[0105] exist Figure 2CIn this configuration, the gas reservoir 326 and the air heater 328 are connected to the airflow assemblies 340B and 340C. In some embodiments, one or more modules 210A-210N may be transported to, out of, and / or between the manipulation chamber 120, the incubator culture chamber 130, the inlet chamber 140, the outlet chamber 150, and the auxiliary chamber 160 for use in cell culture-related activities. For example, one or more modules 210A-210N may be removed from the incubator culture chamber 130 for handling or manipulation within the manipulation chamber 120 along direction 292 (e.g., via the manipulator assembly 450, which will be discussed below). More specifically, the incubator culture chamber 130 may include a structure 294, such as a movable structure (e.g., one or more sliding doors, drawers, etc.), which may be opened (e.g., via the manipulator assembly 450) to allow the manipulator assembly 450 to remove one or more modules 210A-210N from the incubator culture chamber 130 for operation. In some embodiments, prior to opening structure 294, the environmental control subsystem 102 may (e.g., via airflow assembly 340A, airflow assembly 340C, heater 354, and / or air absorber 352) adjust the environmental conditions within the incubator culture chamber 130 and the manipulation chamber 120 to the same target environmental conditions. Thus, when structure 294 is opened, the environmental conditions within the incubator culture chamber 130 and the manipulation chamber 120 can be identical or balanced, thereby preventing fluctuations in environmental conditions within the incubator culture chamber 130 and the manipulation chamber 120 during transport, movement, and / or retrieval of biological samples for manipulation, processing, culture, and / or storage.

[0106] As noted above, when structure 294 is closed, the manipulation chamber 120 and the incubator culture chamber 130 can be structurally and / or fluidly isolated from each other, allowing the environmental control subsystem 102 to flexibly and independently control the environmental conditions within the manipulation chamber 120 and another environmental condition within the incubator culture chamber 130. Advantageously, this provides the automated incubator system 100 with the ability to maintain different environmental conditions within the manipulation chamber 120 and the incubator culture chamber 130 for different applications or cell culture activities.

[0107] In some embodiments, structure 294 can be opened and closed by manipulator assembly 450, and / or otherwise controlled by automated incubator system 100. For example, manipulator assembly 450 can press a button on structure 294 to trigger structure 294 to move along a track (e.g., by motor operation), thereby isolating or fluidly connecting manipulator chamber 120 and incubator culture chamber 130. In some embodiments, structure 294 may include and / or be associated with a mechanical seal (e.g., a gasket) to prevent air exchange between manipulator chamber 120 and incubator culture chamber 130 when structure 294 is closed. Thus, manipulator chamber 120 and incubator culture chamber 130 can be fluidly isolated from each other, thereby allowing the environmental conditions within manipulator chamber 120 and incubator culture chamber 130 to be controlled separately when structure 294 is closed. Notably, environmental control subsystem 102 can also independently control the environmental conditions within inlet chamber 140, outlet chamber 150, and / or accessory chamber 160. As will be discussed regarding Figure 3B As described, when the air composition deviates from the expected value by more than a threshold, the air tank 326 can be used to quickly restore the air composition in the manipulation chamber 120, the incubator culture chamber 130, the inlet chamber 140, the outlet chamber 150, and / or the auxiliary chamber 160.

[0108] Figure 2D The diagram illustrates along Figure 2B of Figures 2D-2D Example cross-sectional view of an automated incubator system 100 taken from a line. Figure 2D The illustration shows that sensor 356 and heater 354 are deployed on or below worktable 460. Figure 2D Further illustrations will be provided. Figure 2E The description of (multiple) visual cameras 412 and (multiple) thermal imagers 418 is further detailed in the text.

[0109] Figure 2E An example perspective view of an automated incubator system 100 according to some embodiments of the present disclosure is illustrated. In some embodiments, Figure 2E The complete integration of the automated incubator system 100 is shown, except that the chamber 230 has been removed. Figure 2EAs illustrated, the intelligent manipulator subsystem 104 includes a visual camera 412, a thermal imager 418, a microscope camera 414, a front-facing microscope camera 416, a worktable 460, and a manipulator assembly 450 deployed on the worktable 460. The intelligent manipulator subsystem 104 can utilize the visual camera 412, the thermal imager 418, and the manipulator assembly 450 to automatically manipulate biological samples. The visual camera 412 and the thermal imager 418 can be deployed around the ceiling associated with the manipulation chamber 120 or around the surface of the worktable 460. In some embodiments, the visual camera 412 and the thermal imager 418 can be movable (e.g., along one or more tracks) or fixed in a specific location.

[0110] although Figure 2E The illustration shows the visual camera 412 and thermal imager 418 integrated with each other, but in some embodiments, they may be mounted separately or otherwise included in other parts. For example, they may be attached to the housing 230 inside the manipulation chamber 120 of the automated incubator system 100. Furthermore, the visual camera 412 and thermal imager 418 may each move along tracks to expand the visual and thermal detection coverage inside the automated incubator system 100. The intelligent manipulator subsystem 104 can control the manipulator assembly 450 to manipulate the biological sample 110 based on thermal imaging data and image data provided by the visual camera 412 and thermal imager 418. As noted above, the manipulator assembly 450 can remove the biological sample from the incubator culture chamber 130 for manipulation and transport the manipulated biological sample back (e.g., via structure 294) to the incubator culture chamber 130. Figure 4 , Figure 5A and Figure 5B The components of the intelligent manipulator subsystem 104 and the manipulations that can be performed on biological samples are described in more detail.

[0111] In operation, the environmental control subsystem 102 can utilize the air quality controller 320, airflow assembly 340A, airflow assembly 340B, and airflow assembly 340C to implement different airflow modes, such as unidirectional, semi-closed, and closed airflow modes. For example, the environmental control subsystem 102 can utilize the airflow assembly 340A to implement a unidirectional airflow mode in the incubator culture chamber 130 to periodically supply intake air stored in an air tank that can be housed inside the housing 220. The environmental control subsystem 102 can simultaneously utilize the airflow assembly 340C to implement a semi-closed or closed airflow mode in the manipulation chamber 120 to periodically circulate at least some of the air within the manipulation chamber 120. As another example, the environmental control subsystem 102 can simultaneously utilize a closed airflow mode to control the air quality in both the manipulation chamber 120 and the incubator culture chamber 130.

[0112] In some embodiments, the rate at which intake air flows into or circulates air within a chamber can be between 0.05 and 20 times per hour, or any value within that range. For example, in a semi-closed or closed airflow mode, the environmental control subsystem 102 can set the Total Air Change (TACH) to 0.1 to 15 times per hour and the Fresh Air Change (FACH) to 0.1 to 3 times per hour. In a unidirectional airflow mode, the environmental control subsystem 102 can set the TACH to 0.1 to 15 times per hour. Furthermore, the environmental control subsystem 102 can adjust the TACH and / or FACH based on the airflow pattern. For example, when switching from a semi-closed airflow mode to a closed airflow mode, the environmental control subsystem 102 can simultaneously reduce both the TACH and FACH.

[0113] As noted above, the environmental control subsystem 102 can set airflow patterns for the respective chambers based on various factors. For example, when the incubator culture chamber 130 is used for a culture activity (e.g., culturing unknown or potentially toxic cells), the environmental control subsystem 102 can utilize a closed airflow mode to control the air quality inside the incubator culture chamber 130 to prevent air leakage from the incubator culture chamber 130 to other chambers and / or the external environment. For example, the user (e.g., via...) Figure 8 The user interface 800 specifies that the culture activities performed inside the incubator culture chamber 130 are related to the culture of toxic cells. For example, the culture activities performed inside the chamber can be automatically determined by the intelligent manipulator subsystem 104 (e.g., using camera assembly 410 and / or thermal imager 418), which will be discussed below. Based on the culture activities specified by the user or determined by the intelligent manipulator subsystem 104, the environmental control subsystem 102 can determine that a closed airflow mode should be used to control the air quality inside the incubator culture chamber 130 to prevent air leakage from the incubator culture chamber 130 to other chambers and / or the external environment. Thus, the automated incubator system 100 can protect not only biological samples from adverse effects associated with the external environment, but also the external environment from biological samples that may be toxic or harmful to the external environment. In a closed airflow mode where air is fully circulated within a specific chamber, the environmental control subsystem 102 can use components such as air absorbers 352 to adjust or control the air composition. However, if the culture activities carried out inside the chamber (e.g., the manipulation chamber 120 and the incubator culture chamber 130) do not involve cells that may be toxic or harmful to the external environment, the environmental control subsystem 102 can determine whether a unidirectional airflow mode or a semi-closed airflow mode can be used to control the air quality inside the chamber.

[0114] In some embodiments, one cell culture activity can be performed inside the incubator culture chamber 130, while another cell culture activity can be performed inside the manipulation chamber 120. For example, the incubator culture chamber 130 can culture human oocytes, while the manipulator assembly 450 inside the manipulation chamber 120 can manipulate human skin tissue or mammalian oocytes. In this example, by controlling the respective environments within the manipulation chamber 120 and the incubator culture chamber 130 (e.g., using different airflow patterns), the automated incubator system 100 can advantageously be allowed to perform different culture activities under correspondingly optimized environmental conditions.

[0115] For example, when the intake air supply is sufficient (e.g., the remaining capacity inside the air tank storing the intake air is high) and / or when a more direct airflow control mechanism (e.g., less air circulation or air quality analysis) is desired, the environmental control subsystem 102 can utilize a unidirectional airflow pattern to control the air quality of one or more of the manipulation chamber 120, incubator culture chamber 130, inlet oral cavity chamber 140, outlet oral cavity chamber 150, and auxiliary chamber 160. For example, the environmental control subsystem 102 can select the airflow pattern for the chamber based on the chamber size. For example, when the chamber size is less than a predetermined value (e.g., 3 liters), the environmental control subsystem 102 can utilize a unidirectional airflow pattern to supply air to the chamber. Additionally and / or optionally, the user can set the airflow pattern for the chamber. For example, the user can utilize... Figure 8 The user interface 800 is used to set the airflow mode for the chamber.

[0116] In some embodiments, the environmental control subsystem 102 can control the air quality within each chamber (e.g., manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160) to achieve a desired quality, as these air qualities may differ from each other due to different operations (e.g., heat dissipation of manipulator components) or processes performed in the respective chambers (e.g., air released or consumed by cells during growth, liquid nitrogen thawing). For example, in the context of cell culture for IVF treatment, the environmental control subsystem 102 can detect and analyze the air quality to control the air quality in each chamber to a temperature of 37°C, humidity of 40%, and an air composition of 5% oxygen, 6% carbon dioxide, and 89% nitrogen. Thus, each of the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and auxiliary chamber 160 can be controlled to restore the same environmental conditions from different environmental conditions.

[0117] In addition to using airflow control mechanisms to control environmental conditions, the environmental control subsystem 102 can also utilize non-airflow control mechanisms, such as air absorbers 352, heaters 354, and sensors 356, to control the environmental conditions inside each chamber. For example, when sensor 356 detects that the temperature at a surface in the manipulation chamber 120 is lower than a desired temperature, the environmental control subsystem 102 can activate heater 354 near that surface to heat the surface. In some embodiments, heater 354 can be integrated with some cooling elements to raise and lower the temperature associated with the chamber. As another example, the environmental control subsystem 102 can activate air absorbers 352 to absorb oxygen, nitrogen, carbon dioxide, etc., from the air, thereby adjusting the air composition in a particular chamber to a desired composition.

[0118] Figure 2F An example perspective view of an automated incubator system 100A according to some embodiments of the present disclosure is illustrated. Unless otherwise indicated, the function and structure of the automated incubator system 100A are similar to those of other systems. Figures 2A-2E The automated incubator system 100 illustrated in the figure is similar. For example, Figure 2F The functions and structures of the components and chambers within can be related to Figures 2A-2E Components and chambers with the same number are identical or roughly similar. For example... Figure 2F As shown, the automatic incubator system 100A structurally includes a control chamber 120, an incubator culture chamber 130, an outlet chamber 150, an auxiliary chamber 160, and an inlet chamber 140A. The inlet chamber 140A includes a transfer compartment 140A-1 and an internal compartment 140A-2.

[0119] Compared to the inlet chamber 140 of the automated incubator system 100, the inlet chamber 140A can be larger. For example, transfer compartments 140-1 and internal compartments 140-2 can each be cuboid in shape, having a length between 4 cm and 6 cm, a width between 4 cm and 6 cm, and a height between 2 cm and 4 cm. Transfer compartments 140A-1 and internal compartments 140A-2 can each have a height between 25 cm and 35 cm (e.g., 30 cm), a width between 25 cm and 35 cm (e.g., 30 cm), and a length between 10 cm and 20 cm (e.g., 15 cm). Advantageously, when transfer compartments 140A-1 and internal compartments 140A-2 are larger, they can allow the automated incubator system 100A to receive larger biological samples and / or modules (e.g., blood bags). In some examples, transfer compartment 140A-1 can meet ISO Class 8 cleanroom requirements. Internal compartment 140A-2 meets ISO Class 7 cleanroom requirements. Operating chamber 120 meets ISO Class 5 cleanroom requirements. Incubator chamber 130 meets ISO Class 5 cleanroom requirements.

[0120] Example Block Diagram of Environment Control Subsystem

[0121] Figure 3A According to some embodiments of this disclosure Figure 1 A block diagram of the environmental control subsystem 102. (See diagram below.) Figure 3A As illustrated, the environmental control subsystem 102 includes one or more air analyzers 310A-310N, an air quality controller 320, one or more airflow components 340A-340N, and a non-airflow control component 350. The non-airflow control component 350 includes an air absorber 352, a heater 354, and a sensor 356. Both the air quality controller 320 and the non-airflow control component 350 can be based on... Figure 4 The thermal control signal 368 described in relation to the intelligent manipulator subsystem 104 is used to control the environmental conditions within the automatic incubator system 100.

[0122] like Figure 3AAs shown, air analyzer 310A can be paired with airflow assembly 340A to detect and control the air quality inside incubator culture chamber 130, and so on (e.g., air analyzer 310N can be paired with airflow assembly 340N to control another chamber). More specifically, air analyzer 310A can analyze air1(t) 374A sampled and directed from the air inside incubator culture chamber 130 by airflow assembly 340A. Therefore, air analyzer 310A can determine the air quality, such as pressure, humidity, temperature, and / or composition, in incubator culture chamber 130 at a specific time. Based on the analysis, air analyzer 310A can generate quality indicators 362A indicating the air quality (e.g., temperature, humidity, pressure, and / or composition) in incubator culture chamber 130.

[0123] Based on quality indicator 362A, air1(t) 374A, intake 372, and / or airflow pattern 364A, air quality controller 320 can generate subsequent air, such as air1(t+1) 376A, which will be supplied to the incubator culture chamber 130 by airflow assembly 340A. For example, when air quality controller 320 determines that the airflow pattern 364A for the incubator culture chamber 130 is a unidirectional airflow pattern, air quality controller 320 can use intake 372 (e.g., air stored in an air canister housed in the housing 220 outside the incubator culture chamber 130) to generate air1(t+1) 376A. Intake 372 may optionally be filtered (e.g., filtered by volatile organic compounds (VOCs)) to generate air1(t+1) 376A. In this example, air quality controller 320 may generate air1(t+1) 376A without recirculating air1(t) 374A. For example, when the air quality controller 320 determines that the airflow mode 364A is a semi-closed airflow mode, the air quality controller 320 can generate air1(t+1)376A based on the intake air 372 and air1(t)374A. More specifically, the air quality controller 320 can filter air1(t)374A to mix it with the intake air 372, thereby generating air1(t+1)376A. For another example, when the air quality controller 320 determines that the airflow mode 364A is a closed airflow mode, the air quality controller 320 can generate air1(t+1)376A based on air1(t)374A without using the intake air 372.

[0124] Based on airflow mode 364A, air quality controller 320 can control airflow assembly 340A to direct air1(t+1)376A to incubator chamber 130. For example, when airflow mode 364A is a closed airflow mode, air quality controller 320 can control airflow assembly 340A to direct air1(t+1)376A to incubator chamber 130 at a lower frequency (e.g., at lower TACH and FACH).

[0125] Furthermore, based on quality indicators 362A-362N, the air quality controller 320 can generate a non-flow control signal 366 to control the non-airflow control component 350, thereby regulating the environmental conditions within the chamber of the automated incubator system 100. For example, when quality indicator 362A indicates that the temperature in the incubator chamber 130 is below a desired level, the air quality controller 320 can generate a non-flow control signal 366 to cause the heater 354 inside the incubator chamber 130 to heat the temperature. As another example, when quality indicator 362A indicates that the carbon dioxide level inside the incubator chamber 130 is higher than a desired level (e.g., 6%) (e.g., 15%), the air quality controller 320 can generate a non-flow control signal 366 to activate the air absorber 352 to absorb carbon dioxide inside the incubator chamber 130 through the airflow component 340A (e.g., the air duct of the airflow component 340A, which can guide carbon dioxide to the air absorber 352 for absorption).

[0126] In some embodiments, the activation level of the air absorber 352 may depend on airflow modes 364A to 364N. For example, when airflow mode 364A is a closed airflow mode, the air quality controller 320 may generate a non-flow control signal 366 to fully activate (e.g., 100% activation) the air absorber 352 to absorb carbon dioxide from the incubator culture chamber 130. When airflow mode 364A is a semi-closed airflow mode, the air quality controller 320 may generate a non-flow control signal 366 to partially activate (e.g., 50% activation) the air absorber 352 to absorb carbon dioxide from the incubator culture chamber 130. When airflow mode 364A is a unidirectional airflow mode, the air quality controller 320 may not activate the air absorber 352 to absorb carbon dioxide from the incubator culture chamber 130. Conversely, the air quality controller 320 can cause the airflow assembly 340A to flow air1(t+1)376A into the incubator culture chamber 130, wherein the air quality controller 320 can generate air1(t+1)376A to reduce the level of carbon dioxide.

[0127] In some embodiments, the air quality controller 320 and the non-airflow control component 350 may further control the environmental conditions in the manipulation chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and / or the auxiliary chamber 160 based on the thermal control signal 368. (See also: Regarding...) Figure 4 As described, the thermal control signal 368 can be generated by the intelligent manipulator subsystem 104 based on real-time object information (e.g., object identity and location) and thermal imaging data (e.g., object temperature). In some embodiments, when the real-time object information and thermal imaging data show that the temperature of the liquid in the pipette held by the manipulator assembly 450 above the stage 460 in the manipulator chamber 120 deviates from the desired temperature, the thermal control signal 368 can cause the air quality controller 320 to generate hotter or colder air, which will flow into the manipulator chamber 120 via the airflow assembly 340C.

[0128] In other embodiments, when real-time object information and thermal imaging data show that the temperature inside a culture dish or vessel containing a biological sample placed at a location on stage 460 deviates from the desired temperature, thermal control signal 368 can cause non-airflow control component 350 to activate heater 354 located at or around the location on stage 460. In both examples, the amount of temperature adjustment can depend on the identity of the biological sample inside the culture dish. For example, when a culture dish placed on stage 460 holds embryos for IVF processing, thermal control signal 368 can cause heater 354 to heat the culture dish to 37°C. Advantageously, by using a non-airflow control component 350 controlled by a thermal control signal 368 and a quality control component 324 (e.g., air filter 330, air tank 326, and / or air heater 328) connected to airflow components 340A-340N to control environmental conditions in a specific chamber and / or at a specific point within the chamber, the automated incubator system 100 can more efficiently (e.g., in a shorter amount of time) and accurately control the air composition, humidity, and / or temperature within the chamber 230.

[0129] Figure 3B The illustrations depict some embodiments according to this disclosure. Figure 3A A block diagram of a part of the environmental control subsystem 102. (See diagram below.) Figure 3BAs illustrated, the air analyzer 310A includes a pressure sensor 312, a composition sensor 314, a temperature sensor 316, and a humidity sensor 318. The air quality controller 320 includes a quality control engine 322 and a quality control component 324. The pressure sensor 312, composition sensor 314, temperature sensor 316, and humidity sensor 318 of the air analyzer 310A can sense and analyze air1(t) 374A from the incubator culture chamber 130 to generate a quality index 362A indicating the air quality in the incubator culture chamber 130.

[0130] The quality control engine 322 can be a combination of hardware, firmware, and software. The quality control engine 322 can set or determine airflow patterns 364A to 364N. Based at least on quality index 362A and thermal control signal 368, the quality control engine 322 can generate a non-flow control signal 366 to the non-airflow control component 350 for controlling environmental conditions within the incubator chamber 130 by adjusting air composition (e.g., using air absorber 352) or temperature (e.g., using heater 354). Based at least on quality index 362A and thermal control signal 368, the quality control engine 322 can generate a quality control signal 378 to control the quality control component 324 to use intake air 372 and air1(t) 374A to generate air1(t+1) 376A.

[0131] Quality control components 324 may include an air tank 326, an air heater 328, and an air filter 330. The air filter 330 may include a volatile organic compound (VOC) filter, a high-efficiency particulate air (HEPA) filter, or other types of filters capable of filtering the air within the automated incubator system 100. Although Figure 3B Not illustrated, but the quality control component 324 may include other air quality control devices, such as a humidifier. A quality control signal 378 may indicate to the quality control component 324 the percentage of intake air 372 to be used, and the amount of air1(t) 374A to be processed (e.g., circulated and filtered) by the quality control component 324 to generate air1(t+1) 376A for the incubator culture chamber 130. The quality control signal 378 may cause the quality control component 324 to generate air1(t+1) 376A to flow through the airflow assembly 340A to the incubator culture chamber 130, thereby maintaining the air quality in the incubator culture chamber 130 at desired conditions. In some embodiments, depending on the stage of cell culture, the quality control engine 322 may generate the quality control signal 378 to adjust the desired conditions at a particular chamber.

[0132] In some embodiments, when the quality control engine 322 determines, based on quality indicator 362A, that a change in air composition exceeds a specific threshold, the quality control engine 322 can rapidly restore the air composition using the gas reservoir 326. For example, when quality indicator 362A indicates that the nitrogen level in the incubator culture chamber 130 has suddenly increased by a certain percentage (e.g., 6%) exceeding a desired level (e.g., 89%) due to the release of liquid nitrogen associated with automated cryopreservation, the quality control engine 322 can generate a quality control signal 378 to cause the gas reservoir 326 to flush air with a lower nitrogen content into the incubator culture chamber 130. Thus, the nitrogen level in the incubator culture chamber 130 can be immediately reduced to the desired level. In this example, the quality control signal 378 can also activate the air heater 328 to direct warmer air toward the chamber where liquid nitrogen is being released. Furthermore, the thermal control signal 368 can cause the quality control engine 322 to generate a non-flow control signal 366 to activate the heater 354, thereby increasing the temperature around the point where liquid nitrogen is being released.

[0133] In some embodiments, when the quality control engine 322 determines, based on quality index 362A, that the temperature within the incubator culture chamber 130 is lower than the desired temperature, the quality control engine 322 can generate a quality control signal 378 to trigger the air heater 328 to generate air1(t+1) 376A, which is heated to or exceeds the desired temperature and flows through the airflow assembly 340A to the incubator culture chamber 130. Advantageously, the air heater 328 and the heater 354 can respectively regulate the temperature within a specific chamber or around a specific point within the chamber through airflow control mechanisms and non-airflow control mechanisms.

[0134] In some embodiments, when the quality control engine 322 determines, based on quality index 362N, that the temperature at certain points on the worktable 460 in the operating chamber 120 is lower than the desired temperature, the quality control engine 322 may generate a quality control signal 378 to trigger the air heater 328 to generate air. n (t+1)376N. air n (t+1)376N can be heated to or above the desired temperature and can flow through the airflow assembly 340N to certain points on the worktable 460 in the operating chamber 120. As noted above, the air heater 328 and heater 354 can advantageously regulate the temperature within or around certain points within a particular chamber through airflow control mechanisms and non-airflow control mechanisms, respectively.

[0135] Example Intelligent Manipulator Subsystem

[0136] Figure 4 The illustrations depict some embodiments according to this disclosure.Figure 1 A block diagram of the intelligent manipulator subsystem 104. (See diagram below.) Figure 4 As illustrated, the intelligent manipulator subsystem 104 includes a camera assembly 410, a thermal imager 418, an object identifier 420, a manipulator motion controller 430, an object temperature controller 440, and a manipulator assembly 450. The camera assembly 410 includes a visual camera 412, a microscope camera 414, and a front-facing microscope camera 416.

[0137] like Figure 4 As illustrated, based on image data 462 generated by camera component 410 and thermal imaging data 464 generated by thermal imager 418, object identifier 420 can generate real-time object information 466. Image data 462 can depict an image associated with an object inside the automated incubator system 100. Thermal imaging data 464 can include thermal information associated with the object. Real-time object information 466 can at least include the identity (e.g., oocyte, embryo, culture dish, pipette, etc.) and location (e.g., position in coordinates defined by the automated incubator system 100) of the object to be manipulated by manipulator component 450.

[0138] Based on real-time object information 466 and thermal imaging data 464, the object temperature controller 440 can generate a thermal control signal 368. This thermal control signal will be used by the air quality controller 320 and non-airflow control components 350 to control the environmental conditions within the automated incubator system 100, such as regarding... Figure 3A and Figure 3B As described, the thermal control signal 368 can cause the air quality controller 320 to deliver air at a specific temperature to a specific chamber, or activate the heater 354 at a specific point within a specific chamber, for controlling environmental conditions in one or more specific areas and culture dishes. Based on real-time object information 466, the manipulator motion controller 430 can generate a motion control signal 468 to control the manipulator assembly 450 to manipulate the biological sample 110. Advantageously, by utilizing the thermal control signal 368 and quality indicators 362A-362N to control the air quality controller 320 and the non-airflow control assembly 350 to regulate environmental conditions within the manipulator chamber 120 and the incubator culture chamber 130, the automated incubator system 100 can more quickly and accurately maintain environmental conditions within the manipulator chamber 120 and the incubator culture chamber 130 under multiple target conditions.

[0139] As noted above, the visual camera 412 and thermal imager 418 may be mounted around the ceiling of the automated incubator system 100 (e.g., attached to the enclosure 230) to broadly monitor areas or points within the manipulation chamber 120, incubator culture chamber 130, inlet chamber 140, outlet chamber 150, and / or auxiliary chamber 160. The microscopic camera 414 and microscopic front-facing camera 416 may be mounted on or integrated with the manipulator assembly 450. In some embodiments, the visual camera 412 may be a charge-coupled device camera, a digital single-lens reflex (DSLR) camera, a video camera, a 3D camera, or any other suitable type of camera, which may generate a portion of image data 462 for obtaining the position of an object to control macroscopic movements of the manipulator assembly 450 (e.g., movement on a centimeter-scale distance, transporting biological sample 110 from the manipulation chamber 120 to the incubator culture chamber 130, etc.).

[0140] In some embodiments, the microscope camera 414 may be a bright-field microscope, phase-contrast microscope, polarizing microscope, inverted microscope, Schmidt objective microscope, optical microscope, or any other type of microscope camera, which may generate a portion of image data 462 for controlling fine movements of the manipulator assembly 450 (e.g., moving and positioning the biological sample 110 at a distance scale of millimeters or smaller for observation, loading, and unloading the biological sample 110 via the microscope front camera 416). The magnification of the microscope camera 414 may be up to 500x, 750x, 1000x, 1500x, 2000x, or any value in between.

[0141] In some embodiments, the front-facing microscope camera 416 may be an electron microscope or any other type of microscope that can generate a portion of image data 462 for controlling the manipulator assembly 450 to perform micromanipulation on the biological sample 110 (e.g., holding a pipette containing the biological sample 110, such as an embryo, aspirating mammalian oocytes, injecting sperm into unfertilized eggs, etc.). The magnification of the front-facing microscope camera 416 may be greater than 1,000x and up to 10,000,000x, or any other value in between.

[0142] In some embodiments, the thermal imager 418 may be a cold infrared camera, an uncooled infrared camera, a long-wave infrared (LWIR) camera, a mid-wave infrared (MWIR) camera, a short-wave infrared (SWIR) camera, or other types of thermal imaging cameras, which can generate thermal imaging data 464 by detecting energy (e.g., infrared energy or heat) for use in visual image conversion to depict the spatial distribution of temperature differences in the automated incubator system 100.

[0143] Based on image data 462 and thermal imaging data 464, object identifier 420 can generate real-time object information 466. More specifically, object identifier 420 may include a feature engine and / or a machine learning model. The feature engine may analyze image data 462 and / or thermal imaging data 464 to extract features (e.g., shape features) associated with the object to be manipulated by manipulator component 450. Based on the extracted features, the machine learning model may generate real-time object information 466 that identifies and locates the object to be manipulated. In some examples, object identifier 420 may include a machine learning model without a feature engine. In these examples, the machine learning model may process image data 462 and / or thermal imaging data 464 (e.g., for feature extraction) and generate real-time object information 466 (e.g., via forward propagation through the model). In some embodiments, the machine learning model may be a support vector machine (“SVM”), a deep learning model, a recurrent neural network (“RNN”), or any other suitable artificial intelligence (“AI”) model. Machine learning models can be trained for applications involving the manipulation of culture dishes, laboratory equipment, and / or the micromanipulation of oocytes, embryos, eggs, sperm, organoids, cells, or tissues.

[0144] Figure 5A The figures illustrate some embodiments according to the present disclosure. Figure 1 A portion of the intelligent manipulator subsystem 104 (e.g., microscope cameras 414-1, 414-2, and 414-3, front-facing microscope camera 416, and manipulator assembly 450) is shown in an example perspective view from different angles. Figure 5A As illustrated, microscope camera 414 and front-facing microscope camera 416 are integrated with manipulator assembly 450. In some embodiments, microscope camera 414-1 is a vertical microscope, 414-2 is a movable manipulator-integrated microscope, and 414-3 is a polarizing inverted microscope.

[0145] Figure 5B The figures illustrate some embodiments according to the present disclosure. Figure 5A An enlarged representation of this part of the intelligent manipulator subsystem 104 illustrated in the figure. (See figure.) Figure 5B As illustrated, a microscope camera 414-2 is attached to a portion of the manipulator assembly 450. A front-facing microscope camera 416 is mounted near the cell picker 520. The cell picker 520 can detect, pick up, puncture, press, contact, probe, or otherwise manipulate the biological sample 110 using the front-facing microscope camera 416. In some embodiments, the cell picker 520 may be an ICSI needle, a biopsy needle, or a laser. In some embodiments, the cell picker 520 and the front-facing microscope camera 416 may be pointed in the same direction (e.g., towards the same biological sample). Figure 5B(Not shown in the diagram) to advantageously enable micromanipulation of biological samples. As noted above, by integrating the intelligent manipulator subsystem 104 (e.g., manipulator component 450, whose motion is controlled by a machine learning model using image data 462 and thermal imaging data 464), the manipulation chamber 120, and the incubator culture chamber 130 within the enclosure 230, the automated incubator system 100 enables simplified and automated cell culture or laboratory processes without human intervention from professionals. Thus, the environment within the enclosure 230 is less likely to fluctuate due to the presence of personnel. With its highly integrated and compact size (e.g., the enclosure has a volume of less than 500 liters), the automated incubator system 100 also powerfully allows for unmanned or remote control for various applications (e.g., underwater cell culture or cell culture inside spacecraft).

[0146] Example Flow Diagram

[0147] Figure 6A This is a method for controlling an incubator system (such as...) according to some embodiments of this disclosure. Figure 1 A flowchart illustrating an example process 600 of environmental conditions in an automated incubator system 100. All or at least some parts of process 600 may be derived from, for example... Figure 1 An automated incubator system 100 is implemented. It should be noted that at least some parts of process 600 can be executed simultaneously, sequentially, or in different orders. Process 600 can provide for detecting environmental conditions in different chambers (e.g., manipulation chamber 120 and incubator culture chamber 130) and adjusting the environmental conditions in different chambers separately using the same or different airflow patterns. Thus, process 600 can be used to achieve more efficient, time-saving, and accurate environmental condition control.

[0148] At block 602, the automated incubator system 100 detects a first environmental condition associated with the first chamber. For example, an air analyzer 310A can detect environmental conditions in the incubator culture chamber 130. These environmental conditions may include temperature, humidity, pressure, and / or air composition in the incubator culture chamber 130.

[0149] At block 604, the automated incubator system 100 detects a second environmental condition associated with the second chamber. For example, air analyzer 310B can detect environmental conditions in the control chamber 120. These environmental conditions may include temperature, humidity, pressure, and / or air composition in the control chamber 120.

[0150] At block 606, the automated incubator system 100 can generate a first airflow and supply it to the first chamber to adjust the first environmental conditions of the first chamber to a first target environmental condition. For example, the air quality controller 320 can generate the first airflow flowing to the incubator culture chamber 130 based on the environmental conditions of the incubator culture chamber 130, the first target environmental condition, and the first airflow pattern. As noted above, the first target environmental condition can specify at least a target temperature, a target humidity, and a target air composition. For example, in the context of IVF treatment using the automated incubator system 100, the target temperature could be 37°C, the target humidity could be 40%, and the target air composition could include 5% oxygen, 6% carbon dioxide, and 89% nitrogen. The first airflow pattern can be selected by the user through a user interface or determined based on different factors discussed above (e.g., the cell culture activities taking place inside the first chamber, the size of the first chamber, and / or the remaining capacity of the air tank supplying air to the first chamber). As noted above, cell culture activities performed inside the first chamber (e.g., culturing unknown cells, culturing toxic cells, culturing mammalian oocytes, manipulating mammalian oocytes, manipulating other biological samples, etc.) can be defined or specified through a user interface or automatically determined by the intelligent manipulator subsystem 104.

[0151] In some embodiments, the first airflow mode can be one of a unidirectional airflow mode, a semi-closed airflow mode, and a closed airflow mode. When the first airflow mode is a unidirectional airflow mode, the air quality controller 320 can generate the first airflow based on the intake 372 without circulating the air within the incubator culture chamber 130. When the first airflow mode is a closed airflow mode, the air quality controller 320 can generate the first airflow by circulating the air within the incubator culture chamber 130 without using the intake 372. The airflow assembly 340A can supply (e.g., guide and direct) the first airflow to the incubator culture chamber 130 to adjust the first environmental conditions of the incubator culture chamber 130 to a first target environmental condition.

[0152] At block 608, the automated incubator system 100 can generate a second airflow and supply it to the second chamber to adjust the second environmental conditions of the second chamber to a second target environmental condition. The second target environmental condition may be the same as or different from the first target environmental condition. For example, the air quality controller 320 can generate a second airflow flowing toward the control chamber 120 based on the environmental conditions of the control chamber 120, the second target environmental condition, and the second airflow pattern. The airflow assembly 340B can supply (e.g., guide and direct) the second airflow to the control chamber 120 to adjust the second environmental conditions of the control chamber 120 to the second target environmental condition.

[0153] Figure 6BThe illustrations depict some embodiments according to this disclosure. Figure 1 The flowchart shows an example implementation of block 606 (and / or block 608) for controlling air quality in an example automated incubator system.

[0154] At block 606-1, the automated incubator system 100 can sample air from the first chamber. For example, the airflow assembly 340A can sample some air (e.g., air1(t)374A) inside the incubator culture chamber 130 and direct it to the housing 220 that houses the air analyzer 310A and the air quality controller 320.

[0155] At block 606-2, the automated incubator system 100 can analyze the air to determine indicators indicating air quality. For example, air analyzer 310A can analyze air1(t) 374A to determine quality indicators 362A that indicate the air quality (e.g., temperature, humidity, pressure, and / or air composition) inside the incubator culture chamber 130.

[0156] At block 606-3, the automated incubator system 100 can generate a quality control signal for the first chamber based on an indicator, a thermal control signal, and a first airflow pattern. For example, based on quality indicator 362A, thermal control signal 368, and airflow pattern 364A, quality control engine 322 can generate a quality control signal 378 to control quality control component 324. More specifically, when quality indicator 362A indicates that the temperature inside the incubator chamber 130 is lower than a target temperature, quality control engine 322 can generate a quality control signal 378 to cause air heater 328 to generate air1(t+1)376A at a temperature higher than air1(t)374A. For example, when the thermal control signal 368 indicates that the temperature at a specific point in the incubator chamber 130 is lower than the target temperature, the quality control engine 322 can generate a quality control signal 378 to cause the quality control component 324 and the airflow component 340A to direct warmer air (e.g., air1(t+1)376A) to the specific point in the incubator chamber 130.

[0157] At block 606-4, the automated incubator system 100 can generate subsequent airflow to the first chamber based at least on a quality control signal. For example, the quality control component 324 can generate air1(t+1)376A based on the quality control signal 378. More specifically, when the airflow mode 364A is a semi-closed or closed airflow mode, the quality control signal 378 can cause the quality control component 324 to generate air1(t+1)376A by circulating and filtering air (e.g., air1(t)374A) from the incubator culture chamber 130. When the airflow mode 364A is a unidirectional airflow mode, the quality control signal 378 can cause the quality control component 324 to generate air1(t+1)376A using the intake 372 without circulating the air within the incubator culture chamber 130.

[0158] At block 606-5, the automated incubator system 100 can release subsequent air into the first chamber based on a first airflow pattern. For example, airflow assembly 340A can guide and direct air1(t+1)376A into the incubator culture chamber 130 based on the airflow pattern used for the incubator culture chamber 130. More specifically, when airflow pattern 364A is a closed airflow pattern, airflow assembly 340A can cause air1(t+1)376A to flow into the incubator culture chamber 130 at a lower frequency (e.g., at lower TACH and FACH) compared to when airflow pattern 364A is a semi-closed airflow pattern.

[0159] Figure 7A This is a flowchart of an example process 700 for controlling a manipulator assembly, such as manipulator assembly 450, to manipulate a biological sample 110 according to some embodiments of this disclosure. All or at least some portions of process 700 may be, for example, by… Figure 1 The intelligent manipulator subsystem 104 is implemented. Process 700 can provide automated manipulation of biological samples 110 without the manual labor of professionals (such as embryologists).

[0160] At block 702, the automated incubator system 100 receives the manipulation task to be performed. For example, the intelligent manipulator subsystem 104 can do so through a user interface (e.g., in...). Figure 8The user interface 800 described herein obtains the manipulation task to be performed from the user. This manipulation task may include transporting biological sample 110 from the inlet chamber 140 to the incubator culture chamber 130, loading and unloading biological sample 110, positioning biological sample 110, holding a pipette containing biological sample 110, injecting sperm into unfertilized eggs, and injecting sperm into unfertilized eggs under the guidance, control, and observation of microscope cameras 414-1, 414-2, and / or 414-3 and a front-facing microscope camera 416, etc. As noted above, in some embodiments, microscope camera 414-1 is a vertical microscope, microscope camera 414-2 is a mobile manipulator integrated microscope, and microscope camera 414-3 is a polarizing inverted microscope.

[0161] At block 704, the automated incubator system 100 acquires image data and thermal imaging data from a camera. For example, the object identifier 420 of the intelligent manipulator subsystem 104 acquires image data 462 generated by the camera assembly 410 and thermal imaging data 464 generated by the thermal imager 418.

[0162] At block 706, the automated incubator system 100 identifies the object to be manipulated and generates object information based on image data and thermal imaging data. For example, object identifier 420 generates real-time object information 466 based on image data 462 and thermal imaging data 464. Real-time object information 466 can identify the object to be manipulated. Real-time object information 466 may include the identity (e.g., oocyte, embryo, culture dish, pipette, etc.) associated with the object to be manipulated by manipulator component 450, temperature, and location information (e.g., position in a coordinate system defined by the automated incubator system 100).

[0163] At block 708, the automated incubator system 100 generates motion control signals based on object information. For example, the manipulator motion controller 430 can generate motion control signals 468 based on real-time object information 466.

[0164] At block 710, the automated incubator system 100 controls the manipulator assembly based on motion control signals. For example, the manipulator motion controller 430 controls the manipulator assembly 450 to manipulate the biological sample 110 based on motion control signals 468 generated at block 708.

[0165] Figure 7B This is a flowchart illustrating an example implementation of block 710 used to control the manipulation of biological sample 110 by the manipulator components. It should be noted that blocks 710-1, 710-2, and 710-3 can be executed simultaneously, sequentially, iteratively, or in different orders.

[0166] At block 710-1, the automated incubator system 100 coarsely controls the manipulator assembly to approach the object. For example, based on a portion of image data 462 generated by the vision camera 412, the manipulator motion controller 430 can generate motion control signals 468 to control the macroscopic movement of the manipulator assembly 450 (e.g., movement on a centimeter-scale distance scale, transporting the biological sample 110 from the incubator culture chamber 130 to the manipulation chamber 120 for manipulation).

[0167] At block 710-2, the automated incubator system 100 finely controls the manipulator assembly to position and approach the object. For example, based on a portion of image data 462 generated by microscope cameras 414 (e.g., microscope cameras 414-1, 414-2, 414-3), the manipulator motion controller 430 can generate motion control signals 468 to control the fine movement of the manipulator assembly 450 (e.g., movement on a distance scale of millimeters or smaller, positioning the biological sample 110 for observation via the front microscope camera 416).

[0168] At block 710-3, the automated incubator system 100 performs micromanipulation on the object. For example, based on a portion of image data 462 generated by the front-facing microscope camera 416 and the microscope camera 414, the manipulator motion controller 430 can generate motion control signals 468 to control the manipulator assembly 450 to perform micromanipulation (e.g., aspiration) on the biological sample 110.

[0169] Example User Interface

[0170] Figure 8 The illustration shows an example of a user interface 800, which allows users to control and / or monitor... Figure 1 An automated incubator system 100. For example... Figure 8As shown, section 802 indicates that the user interface 800 is displaying information about a manipulation chamber (e.g., manipulation chamber 120). Section 804 shows that the environmental control subsystem 102 is using a closed airflow mode to control the air quality inside the manipulation chamber 120. Section 806 shows a manipulation task performed by the manipulator assembly 450 inside the manipulation chamber 120. In some embodiments, section 806 allows the user to specify cell culture activities to be performed inside the manipulation chamber 120. When section 802 switches from "manipulation chamber" to "incubator culture chamber," section 806 can also allow the user to specify cell culture activities to be performed inside another chamber (e.g., incubator culture chamber 130). As noted above, based on the cell culture activities specified by the user in a particular chamber, the environmental control subsystem 102 can determine an airflow mode (e.g., closed airflow mode, unidirectional airflow mode, and semi-closed airflow mode) for the particular chamber to supply airflow to regulate environmental conditions. Here, section 806 shows the manipulation task being performed as "injecting sperm into unfertilized eggs for IVF treatment." Section 808 displays a message reminding the user to manipulate the environmental conditions within chamber 120. Here, section 808 displays "None. Environmental conditions are well controlled."

[0171] Section 810 illustrates the environmental conditions within the automated incubator system 100. More specifically, section 810 illustrates the air quality within the manipulation chamber 120. Here, section 810 illustrates that the air composition within the manipulation chamber 120 comprises 5% oxygen, 6% carbon dioxide, and 89% nitrogen. Furthermore, section 810 illustrates that the humidity within the manipulation chamber 120 is 40% and the temperature is 37°C. Section 812 allows the user to navigate to monitor and / or control the environmental conditions in other chambers within the automated incubator system 100. Here, section 812 indicates "view other chambers". In some embodiments, the automated incubator system 100 (e.g., environmental control subsystem 102) can control the humidity within the manipulation chamber 120 and / or the incubator culture chamber 130 to a range of approximately 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, or any value between these ranges. In some embodiments, the automated incubator system 100 (e.g., environmental control subsystem 102) can control the nitrogen level in the manipulation chamber 120 and / or the incubator culture chamber 130 to a range of approximately 35%, 85%, 86%, 87%, 89%, 90%, 91%, 92%, 93%, 94%, or any value between these ranges.

[0172] Example System

[0173] Figure 9The overall architecture of the example system is depicted. In some embodiments, the system can be used to perform the functionality described herein. In some embodiments, the system can be an automated incubator system 100, which includes an arrangement of computer hardware and software configured to implement aspects of the present disclosure. The automated incubator system 100 may include more than Figure 9 The diagram shows more (or fewer) of those elements. However, it is not necessary to show all of these elements in order to provide a feasible disclosure.

[0174] As illustrated, the automated incubator system 100 includes a processor 902, a power supply 904, a network interface 906, an air source assembly 908, a data storage unit 910, an intelligent manipulator subsystem 104, and an environmental control subsystem 102, all of which can communicate with each other via a communication bus 912. The intelligent manipulator subsystem 104 can be configured to access each of the manipulator chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and / or the auxiliary chamber 160. The environmental control subsystem 102 can be configured to control the environmental conditions within each of the manipulator chamber 120, the incubator culture chamber 130, the inlet oral cavity chamber 140, the outlet oral cavity chamber 150, and / or the auxiliary chamber 160.

[0175] Network interface 906 can provide connectivity to one or more networks or computing systems, and thus enables the automated incubator system 100 to connect to other computing systems, interfaces (such as...) Figure 8 The user interface 800 or service receives and sends information and instructions to it. In some embodiments, the automated incubator system 100 may be configured to handle requests from other devices or modules, such as requests to adjust environmental conditions to desired conditions specified by the user. The data repository 910 may illustratively be any non-transitory computer-readable data repository, and in different embodiments may store... Figure 9 Any or all of the elements depicted in the text that are loaded into memory 920.

[0176] Processor 902 can also communicate with memory 920. Memory 920 may contain computer program instructions (in some embodiments, grouped into modules or components) that processor 902 can execute to implement one or more embodiments. Memory 920 typically includes RAM, ROM, and / or other persistent, auxiliary, or non-transitory computer-readable media. Memory 920 may store operating system 922, which provides computer program instructions for processor 902 to use in the overall management and operation of automated incubator system 100. Memory 920 may also store specific computer-executable instructions and other information (which may be referred to herein as “modules” or “engines”) for implementing aspects of this disclosure. For example, memory 920 may include feature engine 926 and machine learning model 928, which intelligent manipulator subsystem 104 can utilize to implement aspects of this disclosure as described above. Memory 920 may also store, for example, user interface module 924, which enables... Figure 8 The user interface 800 displays information. During different operations, all modules or elements loaded into the memory 920 can also be stored in the data repository 910.

[0177] It needs to be recognized that Figure 9 Many of the components described are optional, and embodiments of the automated incubator system 100 may combine or not combine components. Furthermore, components need not be independent or discrete. Components may also be reorganized, combined, and / or integrated. For example, Figure 3A The air analyzers 310A-310N can be combined and integrated to save hardware resources (e.g., pressure sensor 312, composition sensor 314, temperature sensor 316, and / or humidity sensor 318). In some embodiments, components illustrated as part of the automated incubator system 100 may be additionally or alternatively included in other computing devices, such that some aspects of this disclosure can be performed by the automated incubator system 100 while others are performed by another computing device.

[0178] All methods and tasks described herein can be performed and fully automated by a computer system. In some cases, a computer system may include multiple different computers or computing devices (e.g., physical servers, workstations, storage arrays, cloud computing resources, etc.) that communicate and interoperate via a network to perform the functions described herein. Each such computing device typically includes one (or more) processors that execute program instructions or modules stored in memory or other non-transitory computer-readable storage media or devices (e.g., solid-state storage devices, disk drives, etc.). The different functions disclosed herein may be embodied in these program instructions or may be implemented in a dedicated circuit system (e.g., an ASIC or FPGA) of the computer system. When a computer system includes multiple computing devices, these devices may (but do not necessarily) be located in the same location. The results of the disclosed methods and tasks can be persistently stored by converting physical storage devices, such as solid-state memory chips or disks, into different states. In some embodiments, the computer system may be a cloud-based computing system whose processing resources are shared by multiple different business entities or other users.

[0179] The processes described herein or illustrated in the accompanying drawings may be initiated in response to an event, such as according to a predetermined or dynamically determined schedule, initiated on demand by a user or system administrator, or in response to some other event. When such a process is initiated, a set of executable program instructions stored on one or more non-transitory computer-readable media (e.g., hard disk drives, flash memory, removable media, etc.) may be loaded into the memory (e.g., RAM) of a server or other computing device. These executable instructions may then be executed by the hardware-based computer processor of the computing device. In some embodiments, such processes, or portions thereof, may be implemented serially or in parallel on multiple computing devices and / or multiple processors.

[0180] Depending on the implementation, certain actions, events, or functions of any process or algorithm described herein may be performed in a different order, or may be added, combined, or omitted entirely (e.g., not all described operations or events are necessary for algorithmic practice). Furthermore, in some embodiments, operations or events may be performed concurrently, for example through multithreading, interrupt handling, multiple processors or processor cores, or other parallel architectures, rather than sequentially.

[0181] The various illustrative logic blocks, modules, routines, and algorithm steps described in conjunction with the embodiments disclosed herein can be implemented as electronic hardware (e.g., ASIC or FPGA devices), computer software running on computer hardware, or a combination of both. Furthermore, the various illustrative logic blocks and modules described in conjunction with the embodiments disclosed herein can be implemented or executed by machines such as processor devices, digital signal processors (“DSPs”), application-specific integrated circuits (“ASICs”), field-programmable gate arrays (“FPGAs”) or other programmable logic devices, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. A processor device may be a microprocessor, but alternatively, it may be a controller, microcontroller, or state machine, a combination thereof, etc. A processor device may include a circuit system configured to process computer-executable instructions. In another embodiment, the processor device includes an FPGA or other programmable device that performs logic operations without processing computer-executable instructions. A processor device may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, a combination of multiple microprocessors, a combination of one or more microprocessors with a DSP core, or any other such configuration. Although this article primarily describes digital technologies, processor devices can also primarily include analog components. For example, some or all of the rendering techniques described herein can be implemented in analog circuit systems or mixed analog and digital circuit systems. The computing environment can include any type of computer system, including but not limited to microprocessor-based computer systems, mainframe computers, digital signal processors, portable computing devices, device controllers, or computing engines within devices, etc.

[0182] Elements of the methods, processes, routines, or algorithms described in conjunction with the embodiments disclosed herein may be embodied directly in hardware, as software modules executed by a processor device, or a combination of both. Software modules may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, removable disk, CD-ROM, or any other form of non-transitory computer-readable storage medium. Exemplary storage media may be coupled to the processor device such that the processor device can read information from and write information to the storage medium. Alternatively, the storage medium may be integrated into the processor device. The processor device and storage medium may reside in an ASIC. The ASIC may reside in a user terminal. Alternatively, the processor device and storage medium may reside as discrete components in the user terminal.

[0183] Unless otherwise expressly stated or understood in the context, the conditional language used herein (such as “can,” “may,” “perhaps,” “may,” “for example,” etc.) is generally intended to convey that certain embodiments include certain features, elements, or steps, while other embodiments do not include those features, elements, or steps. Therefore, such conditional language is not generally intended to imply that a feature, element, or step is necessary in any way for one or more embodiments, or that one or more embodiments necessarily include logic (regardless of whether there is additional input or prompting) for determining whether such features, elements, or steps are included or whether they are performed in any particular embodiment. The terms “comprising,” “including,” “having,” etc., are synonymous and used in an inclusive, open-ended manner, and do not exclude other elements, features, actions, operations, etc. Furthermore, the use of the term “or” implies inclusion (not exclusivity), so, for example, when used to connect a series of elements, the term “or” means one, some, or all of the elements in the list.

[0184] Separative language such as “at least one of X, Y, or Z”, unless otherwise explicitly stated, should be understood in context as generally used to indicate that an item, term, etc., can be X, Y, or Z, or any combination thereof (e.g., X, Y, or Z). Therefore, such separate language is generally not intended, nor should it imply, that some embodiments require at least one of X, Y, and Z to be present.

[0185] While the foregoing detailed description has shown, described, and pointed out novel features applied to various embodiments, it will be understood that different omissions, substitutions, and changes may be made to the form and details of the illustrated apparatus or algorithm without departing from the spirit of this disclosure. As will be appreciated, some embodiments described herein may be embodied in a form that does not provide all the features and benefits set forth herein, as some features may be used or practiced separately from other features. All modifications within the equivalent meaning and scope of the claims should be covered within their scope.

Claims

1. A system for cell culture within a chamber, said chamber structurally housing at least a first chamber, a second chamber, and at least a portion of an environmental control subsystem, said system comprising: The first chamber is configured to store a plurality of culture dishes containing biological samples; The second chamber is adjacent to the first chamber and is fluidly isolated from the first chamber by means of one or more first movable structures based on the first movable structures being in a closed configuration, wherein the second chamber is configured to house at least a manipulator assembly for manipulating the plurality of culture vessels; as well as The environmental control subsystem controls the corresponding environments within the first chamber and the second chamber, respectively, and is configured to: The first environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the first chamber. A second environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the second chamber. A first airflow is supplied to the first chamber via a first airflow pattern determined based on a first cell culture activity performed inside the first chamber, so as to adjust the first environmental conditions to a first target environmental condition. as well as A second airflow is supplied to the second chamber via a second airflow pattern determined based on a second cell culture activity conducted inside the second chamber, in order to adjust the second environmental conditions to a second target environmental condition.

2. The system of claim 1, wherein the environmental control subsystem includes a housing that houses at least a portion of an air quality controller, wherein the housing is located outside the enclosure, and wherein the air quality controller is configured to supply the first airflow and the second airflow.

3. The system of claim 2, wherein the air quality controller comprises an air heater, a humidifier, a volatile organic compound (VOC) filter, a high-efficiency particulate air (HEPA) filter, an oxygen absorber, and a carbon dioxide absorber.

4. The system of claim 3, wherein the environmental control subsystem comprises a first airflow assembly and a second airflow assembly, and wherein: The first airflow assembly supplies the first airflow to the first chamber to adjust the first environmental conditions to the first target environmental conditions; as well as The second airflow assembly supplies the second airflow to the second chamber to adjust the second environmental conditions to the second target environmental conditions.

5. The system of claim 4, wherein a first end of the first airflow assembly is located inside the housing, and a second end of the first airflow assembly is located inside the first cavity; and wherein a first end of the second airflow assembly is located inside the housing, and a second end of the second airflow assembly is located inside the second cavity.

6. The system of claim 5, wherein the environmental control subsystem includes a plurality of sensors configured to detect the first environmental condition and the second environmental condition, and wherein the plurality of sensors are housed in the housing and include a pressure sensor, a temperature sensor, a humidity sensor and an air composition sensor.

7. The system according to claim 1, wherein when the first airflow mode is a unidirectional airflow mode, supplying the first airflow includes: Air is injected from the air tank without circulating the air inside the first chamber.

8. The system of claim 7, wherein the environmental control subsystem includes a storage tank different from the air tank, and wherein the environmental control subsystem is further configured to: Determine that the current air composition in the first chamber deviates from the air composition specified by the first target environmental conditions by more than a predetermined threshold; and In response to determining that the current air composition of the first chamber deviates from the air composition specified by the first target environmental conditions, the gas storage tank is used to inject air into the first chamber to adjust the current air composition of the first chamber to the air composition specified by the first target environmental conditions.

9. The system according to claim 1, wherein when the first airflow mode is a closed airflow mode, supplying the first airflow includes: This allows the air inside the first chamber to circulate without injecting air from the air tank.

10. The system according to claim 1, wherein when the first airflow mode is a semi-closed airflow mode, supplying the first airflow includes: The air inside the first chamber is circulated, and intake air is injected from the air tank according to a predetermined ratio.

11. The system according to claim 1, wherein the first airflow mode is a unidirectional airflow mode, and the second airflow mode is a semi-closed airflow mode or a closed airflow mode.

12. The system of claim 1, wherein the first cell culture activity performed inside the first chamber comprises culturing unknown cells or cells toxic to the environment outside the chamber.

13. The system of claim 1, wherein the environmental control subsystem includes a first heater deployed inside the first chamber, and wherein the environmental control subsystem is further configured to activate the first heater to adjust the current temperature of the first chamber to a temperature specified by the first target environmental conditions.

14. The system of claim 1, wherein the environmental control subsystem includes a first air absorber deployed outside the first chamber, and wherein the environmental control subsystem activates the first air absorber based on the first airflow pattern to adjust the current air composition of the first chamber to the air composition specified by the first target environmental conditions.

15. The system of claim 1, wherein the temperature specified by the first target environmental conditions is between 36.5°C and 37.5°C, the humidity specified by the first target environmental conditions is between 38% and 42%, and the air composition specified by the first target environmental conditions comprises 5%-7% oxygen, 5%-10% carbon dioxide, and 88%-90% nitrogen.

16. The system of claim 1, wherein the total volume of the first chamber and the second chamber is less than 500 liters.

17. The system of claim 1, wherein supplying the first airflow comprises: The intake air from the air tank and / or the air inside the first chamber is filtered using a volatile organic compound (VOC) filter and a high-efficiency particulate air (HEPA) filter.

18. The system of claim 1, wherein the environmental control subsystem is further configured to determine the first airflow pattern based at least on the size of the first chamber or the remaining capacity of the air tank supplying the first airflow.

19. The system of claim 1, wherein the environmental control subsystem is further configured to determine the second airflow pattern based at least on the size of the second chamber or the remaining capacity of the air tank supplying the second airflow.

20. The system according to claim 1, wherein: When the first airflow mode is a unidirectional airflow mode, the environmental control subsystem is further configured to control the total annual air exchange rate (TACH) associated with the first chamber, but not the fresh air exchange rate (FACH) associated with the first chamber; and When the first airflow mode is a semi-closed airflow mode or a closed airflow mode, the environmental control subsystem is also configured to control the TACH associated with the first chamber and the FACH associated with the first chamber.

21. The system of claim 1, further comprising an intelligent manipulator subsystem, the intelligent manipulator subsystem including the manipulator assembly, camera assembly, thermal imager, one or more processors and a non-transitory computer storage medium storing instructions, and an object temperature controller, wherein: The camera component is configured to generate image data; The thermal imager is configured to generate thermal imaging data; The one or more processors are configured to execute instructions to generate real-time information associated with one or more objects to be manipulated by the manipulator component, based on the image data and the thermal imaging data via a machine learning model. as well as The object temperature controller is configured to generate one or more thermal control signals based on the thermal imaging data and the real-time information. The environmental control subsystem further supplies the first airflow and the second airflow based on the one or more thermal control signals.

22. The system of claim 21, wherein the environmental control subsystem further supplies the first airflow and the second airflow based on the one or more thermal control signals.

23. The system of claim 21, wherein the machine learning model is configured to: extract features associated with the one or more objects based on the image data and / or the thermal imaging data, and generate the real-time information based on the features.

24. The system according to claim 1, further comprising: A third chamber, configured for cryopreservation or thawing procedures, wherein the third chamber is adjacent to the second chamber and is fluidly isolated from the second chamber by one or more second movable structures based on the closed configuration; and wherein the environmental control subsystem is further configured to: A third environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the third chamber. as well as A third airflow is supplied to the third chamber via a third airflow pattern determined based on a third cell culture activity conducted inside the third chamber, in order to adjust the third environmental conditions to a third target environmental condition.

25. A method implemented by a microsystem for cell culture, wherein the microsystem comprises: A first chamber, configured to store a plurality of culture dishes containing biological samples; And a second chamber configured to house at least a manipulator assembly for manipulating the plurality of culture dishes, the method comprising: The first environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the first chamber. A second environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the second chamber. A first airflow is supplied to the first chamber via a first airflow pattern determined based on a first cell culture activity conducted inside the first chamber, to adjust the first environmental conditions to a first target environmental condition; and A second airflow is supplied to the second chamber based on a second airflow pattern determined by a second cell culture activity conducted inside the second chamber, so as to adjust the second environmental conditions to the second target environmental conditions.

26. The method of claim 25, wherein when the first airflow mode is a unidirectional airflow mode, supplying the first airflow comprises: Air is injected from the air tank without circulating the air inside the first chamber.

27. A system for cell culture within a chamber, said chamber structurally housing at least a first chamber, a second chamber, and at least a portion of an environmental control subsystem, said system comprising: A first chamber, configured to store a plurality of culture dishes containing biological samples; A second chamber, adjacent to the first chamber and fluidly isolated from the first chamber by one or more first movable structures based on the first movable structures being in a closed configuration, wherein the second chamber is configured to house at least a manipulator assembly for manipulating the plurality of culture vessels; as well as An environmental control subsystem is configured as follows: The first environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the first chamber. A second environmental condition is detected, which specifies the current temperature, current humidity, and current air composition of the second chamber. A first airflow is supplied to the first chamber via a first airflow pattern to adjust the first environmental conditions to a first target environmental condition; as well as A second airflow is supplied to the second chamber via a second airflow mode to adjust the second environmental conditions to the second target environmental conditions. in: When the first airflow mode is a unidirectional airflow mode, supplying the first airflow includes: injecting air from an air tank without circulating the air inside the first chamber; When the first airflow mode is a closed airflow mode, supplying the first airflow includes: circulating the air inside the first chamber without injecting air from the air tank; and When the first airflow mode is a semi-closed airflow mode, supplying the first airflow includes: circulating the air inside the first chamber and injecting intake air from the air tank according to a predetermined ratio.

28. The system of claim 27, wherein the environmental control subsystem is further configured to: The first airflow pattern is determined based on a first cell culture activity conducted inside the first chamber; and The second airflow pattern is determined based on the second cell culture activity carried out inside the second chamber.

29. The system of claim 28, wherein the first cell culture activity comprises culturing unknown cells or cells toxic to the environment outside the enclosure.

30. The system of claim 28, wherein the second cell culture activity comprises manipulating oocytes, embryos, eggs, or sperm.

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