Search

WO-2026097053-A1 - MIMICKING PHYSIOLOGICAL OXYGEN LEVELS IN A CULTURE MEDIUM OF AT LEAST ONE ORGAN-ON-A-CHIP MODULE

WO2026097053A1WO 2026097053 A1WO2026097053 A1WO 2026097053A1WO-2026097053-A1

Abstract

An organ-on-a-chip (OoC) platform can link one or more OoC modules in parallel, mimicking oxygen levels of cultures with biological materials housed therein in each OoC module. Each OoC module can include an oxygen sensor; an oxygen scavenger to decrease an oxygen level within the culture medium surrounding the at least one type of biological material. Each OoC module can be connected to a controller, the controller comprising: a memory storing instructions; and a processor configured to access the memory to execute the instructions to at least: for each of the at least one OoC module, ensure that the oxygen level of the culture medium surrounding the at least one type of biological material is physiological based on control of the oxygen scavenger.

Inventors

  • ZHANG, Yu Shrike
  • JIANG, NAN
  • YING, Guoliang

Assignees

  • THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

Dates

Publication Date
20260507
Application Date
20251104
Priority Date
20241104

Claims (20)

  1. 1 . A system comprising: at least one organ-on-a-chip module, each of the at least one organ-on-a-chip module hosting at least one type of biological material within a culture medium; each of the at least one organ-on-a-chip module comprises: an oxygen sensor; and at least one oxygen scavenger configured to decrease an oxygen level within at least a portion of the culture medium surrounding the at least one type of biological material; and each of the at least one organ-on-a-chip module connected to a controller, the controller comprising: a memory storing instructions; and a processor configured to access the memory to execute the instructions to at least: for each of the at least one organ-on-a-chip module, ensure that the oxygen level of at least the portion of the culture medium surrounding the at least one type of biological material is at least within a predefined range from greater than 0% to less than 21% based on recordings from the oxygen sensor and control of the at least one oxygen scavenger.
  2. 2. The system of claim 1 , wherein for each of the at least one organ-on-a-chip module, the processor ensures that the oxygen level of at least the culture medium surrounding the at least one type of biological material is within the predefined range from greater than 0% to less than 21 % by: receiving a recording of the oxygen level of at least the the culture medium surrounding the at least one type of biological material at a time; determining the oxygen level of the culture medium surrounding the at least one type of biological material at the time based on the recording; and determining whether the oxygen level of the culture medium surrounding the at least one type of biological material at the time is within a target oxygen level range for the at least one type of biological material. BWH2025-025
  3. 3. The system of claim 2, wherein: when the oxygen level of the culture medium surrounding the at least one type of biological material at the time matches the target oxygen level for the at least one type of biological material, receive another recording at another time; and when the oxygen level of the culture medium surrounding the at least one type of biological material at the time does not match the target oxygen levels for the at least one type of biological material: take a corrective action by regulating the at least one oxygen scavenger to ensure that the oxygen level of the culture medium surrounding the at least one type of biological material matches the target oxygen level for the at least one type of biological material; and receive another recording at the other time.
  4. 4. The system of claim 3, wherein the at least one type of biological material comprises alveoli microtissue, arterial microtissue, bone microtissue, liver microtissue, kidney microtissue, gut microtissue, and/or vein microtissue.
  5. 5. The system of claim 3, wherein a target oxygen level range related to different types of biological materials comprises alveoli microtissue froml 2.5-13.5%, arterial microtissue from 12.5-13.5%, bone microtissue from 6.5-7.5%, liver microtissue from 12.5-13.5%, kidney microtissue from 5.5-6.5%, gut microtissue from 7.5-8.5%, and/or vein microtissue from 2.5-3.5%.
  6. 6. The system of claim 1 , wherein the at least one organ-on-a-chip module comprises at least two organ-on-a-chip modules connected in parallel.
  7. 7. The system of claim 6, wherein the at least two organ-on-a-chip modules are used for drug screening and the oxygen level affects the drug screening in each of the at least two organ-on-a-chip modules.
  8. 8. The system of claim 1 , wherein the at least one type of biological material comprises a cell and/or a tissue and the at least one organ-on-a-chip simulates a physiological microenvironment for the biological material. BWH2025-025
  9. 9. The system of claim 1 , wherein the oxygen sensor detects an amount of dissolved oxygen in the culture medium within the at least one organ-on-a-chip module.
  10. 10. The system of claim 9, wherein the at least one oxygen scavenger is configured to down-regulate the amount of the dissolved oxygen in the culture medium, wherein at least one oxygen generator is configured to up-regulate the amount of the dissolved oxygen in the culture medium.
  11. 11. A method for controlling an oxygen level of a culture medium surrounding at least one type of biological material housed by at least one organ-on-a-chip module, the method comprising: receiving, by a system comprising a processor, a recording from an oxygen sensor within the culture medium indicative of the oxygen level of the culture medium; determining, by the system, whether the oxygen level of the culture medium needs to be adjusted to a value from greater than 0% to less than 21 %; and when the oxygen level of the culture medium needs to be adjusted to a value from greater than 0% to less than 21%, controlling, by the system, at least one oxygen scavenger within the culture medium to ensure that the oxygen level of the culture medium is the value.
  12. 12. The method of claim 11 , wherein another at least one organ-on-a-chip module comprising another part of the other medium surrounding another biological material is connected in parallel to the at least one organ-on-a-chip module, the method further comprises: receiving, by the system, another recording from another oxygen sensor within another part of the part of the medium surrounding the other biological material indicative of another oxygen level of the other part of the culture medium; determining, by the system, whether the other oxygen level of the other part of the culture medium needs to be adjusted to another value is from greater than 0% to less than 21 %; and when the other oxygen level of the other part of the culture medium needs to be adjusted to the other value from greater than 0% to less than 21%, controlling, by BWH2025-025 the system, at least another oxygen scavenger within the other part of the culture medium to ensure that the other oxygen level of the other part of the culture medium is the other value.
  13. 13. The method of claim 1 1 , wherein the at least one organ-on-a-chip module comprises the oxygen sensor; the at least one oxygen scavenger configured to decrease an oxygen level within the culture medium surrounding the at least one type of biological material; and at least one oxygen generator configured to increase the oxygen level within the culture medium surrounding the at least one type of biological material.
  14. 14. The method of claim 1 1 , wherein the controlling the at least one oxygen scavenger within the culture medium to ensure that the oxygen level of the culture medium is the value comprises: determining whether the oxygen level of the culture medium is within a target oxygen level range for the at least one type of biological material at a time.
  15. 15. The method of claim 14, wherein: when the oxygen level of the culture medium at the time matches the target oxygen level for the at least one type of biological material, receiving another recording at another time; and when the oxygen level of the culture medium surrounding the at least one type of biological material at the time does not match the target oxygen levels for the at least one type of biological material: take a corrective action by regulating the at least one oxygen scavenger to ensure that the oxygen level of the culture medium matches the target oxygen level for the at least one type of biological material; and receive another recording at the other time.
  16. 16. The method of claim 15, wherein the at least one type of biological material comprises alveoli microtissue, arterial microtissue, bone microtissue, liver microtissue, kidney microtissue, gut microtissue, and/or vein microtissue. BWH2025-025
  17. 17. The method of claim 15, wherein a target oxygen level range related to different types of biological materials comprises alveoli microtissue -12.5-13.5%, arterial microtissue - 12.5-13.5%, bone microtissue - 6.5-7.5%, liver microtissue - 12.5-13.5%, kidney microtissue - 5.5-6.5%, gut microtissue - 7.5-8.5%, and/or vein microtissue - 2.5-3.5%.
  18. 18. The method of claim 11 , wherein the at least one type of biological material comprises a cell and/or a tissue and the at least one organ-on-a-chip simulates a physiological microenvironment for the biological material.
  19. 19. The method of claim 11 , wherein the oxygen sensor detects an amount of dissolved oxygen in the culture medium within the at least one organ-on-a-chip module.
  20. 20. The method of claim 19, wherein the at least one oxygen scavenger is configured to down-regulate the amount of the dissolved oxygen in the culture medium and the at least one oxygen generator configured to up-regulate the amount of the dissolved oxygen in the culture medium.

Description

BWH2025-025 NONPROVISIONAL APPLICATION MIMICKING PHYSIOLOGICAL OXYGEN LEVELS IN A CULTURE MEDIUM OF AT LEAST ONE ORGAN-ON-A-CHIP MODULE GOVERNMENT SUPPORT [0001] This invention was made with government support under 2225698 and 1936105 awarded by the National Science Foundation and 5R01 EB028143-04, 3R01 HL166522-02S1 , 5UG3TR003274-02, 5R00CA201603-05, 5R21 EB025270-03, 5R01 CA282451 -02, 5R01 HL153857-05, 5UH3TR003274-05, and 1 R21 HL168656- 01 A1 awarded by the National Institutes of Health. The government has certain rights in the invention. Related Applications [0002] This application claims priority to U.S. Provisional Application Serial No. 63/716,106, filed November 4, 2024, entitled “CLOSED-LOOP MODULAR MULTIORGAN-ON-CHIPS PLATFORM AND USES THEREOF”. The entirety of this provisional application is hereby incorporated by reference for all purposes. Technical Field [0003] This disclosure relates generally to organ-on-a-chip (OoC) modules, and more specifically to systems and methods that can mimic physiological oxygen levels of biological materials in a culture medium of at least one OoC module. Background [0004] An organ-on-a-chip (OoC) platform can be used to study disease, test drugs, assess toxicity, and the like. To do so, the OoC platform arranges one or more OoC modules, each which mimics one or more structures and/or functions of microenvironments of one or more biological materials, in parallel such that a single culture medium can flow through each of the one or more OoC modules. Each of the OoC modules can house a unique biological material within the culture medium. [0005] Current OoC platforms cannot truly mimic the microenvironments of the one or more biological materials within the culture medium at least because current OoC platforms do not provide physiologically appropriate oxygen level(s) to each OoC module. The appropriate oxygen level is critically important to maintain BWH2025-025 functions and allow modulation of behaviors of the one or more biological materials. OoC platforms tend to be housed in incubators that are supplied with an oxygen level of 21%. In such situations, every OoC module in the standard OoC platforms is exposed to the ambient incubator oxygen level of 21 %. However, a 21 % oxygen level is not a physiologically appropriate oxygen level for biological materials within the human body. The physiological oxygen levels in the human body are each greater than 0% and less than 21 % (e.g., alveoli - 13%, artery - 13%, bone - 7%, liver - 13%, kidney - 6%, gut - 8%, vein - 3%). As such, the oxygen level of 21 % cannot accurately model features of one or more biological materials in the human body (e.g., metabolic activities) to study disease, test drugs, assess toxicity, and the like, accurately. Summary [0006] Described herein are systems and methods that can mimic physiological oxygen levels of one or more biological materials (e.g., cells, tissues, and/or organs) in a culture medium in one or more organ-on-a-chip (OoC) module. The one or more OoC modules can be arranged in parallel in an OoC platform. [0007] In an aspect, the present disclosure can include a system that can mimic oxygen levels of one or more physiological microenvironments of one or more biological materials (e.g., cells, tissues, and/or organs) in an OoC platform (including one or more OoC module). The system can include the at least one OoC module, each of the at least one OoC module hosting at least one type of biological material within a culture medium. Each of the at least one OoC module can include: an oxygen sensor and at least one oxygen scavenger configured to decrease an oxygen level within the culture medium surrounding the at least one type of biological material. Each of the at least one OoC module cam be connected to a controller. The controller includes a memory storing instructions; and a processor configured to access the memory to execute the instructions to at least: for each of the at least one OoC module, ensure that the oxygen level of the culture medium surrounding the at least one type of biological material is a value from greater than 0% to less than 21 % based on recordings from the oxygen sensor and control of the at least one oxygen scavenger. [0008] In another aspect, the present disclosure can include a method for controlling an oxygen level of a culture medium surrounding at least one type of BWH2025-025 biological material housed by at least one OoC module. The method can include: receiving, by a system comprising a processor, a recording from an oxygen sensor within the culture medium indicative of the oxygen level of at least a portion of the culture medium; determining, by the system, whether the oxygen level of the culture medium needs to be adjusted to a value from greater than 0% to less than 21 %; and when the oxygen level of the culture medium needs to be adjusted to a value from greater than 0% to less than 21%, and controlling, by the system, at leas