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EP-4741824-A1 - SYSTEM AND METHOD FOR LONGITUDINAL ANALYSIS OF AN ORGANOID

EP4741824A1EP 4741824 A1EP4741824 A1EP 4741824A1EP-4741824-A1

Abstract

A system (102) for longitudinal analysis of an organoid includes a region (106) configured to support a Microelectrode Array (MEA) device (108) carrying an organoid for longitudinal analysis. The MEA device (108) includes a MEA supporting the organoid, a well configured to hold perfusion media for the organoid, a port for supplying the perfusion media to the well, and nodes in the MEA for sensing electrophysiological (EP) signals produced by the organoid from an interior of the organoid. The system (102) further includes a perfusion media interface to a perfusion system (114). The system (102) further includes a computing system (126) configured to identify events in the EP signals for analysis based on predetermined criteria. The identified events include less than an entirety of each of the EP signals, provide a summary of the identified events, and analyze a user selected set of the identified events in the summary.

Inventors

  • COLLAZO, Julio Alvarez
  • GREEN, James Walter
  • MEENTS, Jannis Enno
  • SAVARD, SERGE
  • Schönecker, Sven-Mark
  • SHETTY, NITYANAND

Assignees

  • Harvard Bioscience, Inc.

Dates

Publication Date
20260513
Application Date
20250806

Claims (15)

  1. A system (102) for longitudinal analysis of an organoid, comprising: a region (106) configured to support a Microelectrode Array (MEA) device (108) carrying an organoid for longitudinal analysis; wherein the MEA device (108) includes a MEA supporting the organoid, a well configured to hold perfusion media for the organoid, a port for supplying the perfusion media to the well, and nodes in the MEA for sensing electrophysiological (EP) signals produced by the organoid from an interior of the organoid; a perfusion media interface (124) to a perfusion system (114); and a computing system (126) configured to identify events in the EP signals for analysis based on predetermined criteria, wherein the identified events include less than an entirety of each of the EP signals, provide a summary of the identified events, and analyze a user selected set of the identified events in the summary.
  2. The system (102) of claim 1, wherein a summary for an identified event includes an identification of a microelectrode of the MEA sensing the event and a time stamp.
  3. The system (102) of claim 2, wherein the computing system (126) presents the summary as links that automatically display an event in response to user selection of the event via a corresponding link.
  4. The system (102) of claim 3, wherein the computing system (126) is configured to process a displayed event based on a user input.
  5. The system (102) of claim 1, further comprising: a perfusion system (114) configured to supply the perfusion media to the MEA device through the perfusion media interface.
  6. The system (102) of claim 5, wherein the computing system (126) is configured to control the perfusion system (114) based on an analysis of the EP signals.
  7. The system (102) of claim 5, wherein the computing system (126) is configured to automatically change a setpoint of the perfusion system (114) based on the analysis of the EP signals.
  8. The system (102) of claim 5, wherein the well is configured to concurrently hold a compound under test (CUT), and further comprising: a CUT interface; and a CUT system (118) configured to supply the CUT to the MEA device (108) through the CUT interface.
  9. The system (102) of claim 8, wherein the computing system (126) is configured to control the CUT system (118) based on the analysis of the EP signals.
  10. The system (102) of claim 8, wherein the computing system (126) is configured to automatically change a setpoint of the CUT system (118) based on the analysis of the EP signals.
  11. The system (102) of claim 1, wherein the MEA device is a mesh MEA device (108).
  12. A method for longitudinal analysis of an organoid, comprising: Introducing (1302) an organoid to a MEA device (108); supplying (1304) perfusion media to the MEA device (108) to maintain organoid viability for the longitudinal analysis; sensing (1306) EP signals produced by the organoid from an inside of the organoid with nodes of the MEA device (108); and processing (1308) the EP signals with a computing system (126), wherein the processing includes identifying events for analysis in the EP signals based on predetermined criteria, providing a summary of the identified events, and analyzing a user selected set of the identified events in the summary.
  13. The method of claim 12, wherein the organoid is a neurological or cardiac organoid, and the identifying includes identifying electrical activity events of the organoid.
  14. The method of claim 13, wherein the electrical activity events for the neurological organoid include one or more of spike, burst, or network activity events, and the electrical activity events for the cardiac organoid include one or more cardiac field potential or beat events.
  15. The method of claim 13, wherein the analyzing includes determining information indicative of a functioning of the organoid based on the identified electrical activity events.

Description

TECHNICAL FIELD The following generally relates to analysis of an organoid, and finds particular application to a system and method for longitudinal analysis of an organoid. BACKGROUND An organoid includes a collection of cells of a specific type (e.g., brain, heart, etc.) grown from a few cells of the tissue itself or stem cells that differentiate into cells of the specific organ and behave similarly to the specific organ. In general, it can be considered a smaller version of the specific organ that exhibits many of the functional, structural, and/or biological complexity of the specific organ. As such, an organoid can be utilized to help understand organ behavior and/or how the organ responds to a stimulus (e.g., electrical, optical, thermal, etc.) and/or a compound under test (CUT) (e.g., a drug or other therapy being evaluated in therapy discovery or safety and toxicology testing applications in therapy development) over time. This has been achieved through in vitro studies in which an organoid is grown on a Microelectrode Array (MEA) and organoid electrical activity, in an absence and/or presence of a stimulus and/or a CUT, is measured through microelectrodes of the MEA, where the electrical activity is indicative of behavior and behavior in response to the stimulus and/or the CUT. In general, an MEA device includes an MEA for growing an organoid, a reservoir for holding perfusion media (which promotes growth of the organoid and provides nourishment to maintain viability of the organoid) and a CUT, a port(s) to supply the perfusion media and the CUT to the reservoir, and electrodes for routing electrophysiological (EP) signals produced by the organoid before, during and/or after a CUT, a stimulus, etc. to an analysis system. The perfusion media and/or CUT is supplied to the reservoir of the mesh MEA using a pump and fluidics or manually. With pump-based perfusion media and CUT approach, the user would program the pumps to supply the perfusion media and CUT to the reservoir, each based on its own schedule. With a manual approach, the user would utilize a pipette or the like to supply the perfusion media and CUT to the reservoir, each based on its own schedule. Non-limiting examples of a mesh MEA device are discussed in Stumpp et al., "Scalable mesh microelectrode arrays for neural spheroids and organoids," Current Directions in Biomedical Engineering, vol. 9, no. 1, 2023, pp. 575-578. https://doi.org/10.1515/cdbme-2023-1144, and McDonald et al. "A mesh microelectrode array for non-invasive electrophysiology within neural organoids," Biosens Bioelectron. 2023 May 15;228:115223. doi: 10.1016/j.bios.2023.115223. Epub 2023 Mar 11. PMID: 36931193. The mesh MEA device of Stumpp et al. is compatible with 60-channel amplifiers and includes a well supporting a polyimide grid mesh containing traces and microelectrodes at nodes, and access ports to fill the volume below the mesh with perfusion media and the CUT. The mesh MEA device of McDonald et al. is compatible with 256-channel amplifiers and includes a well supporting a central "spider-web-like" mesh containing microelectrodes sparsely distributed across the region, and access ports to fill the volume below the mesh with perfusion media and the CUT. The analysis system stores, displays, and provides tools for analyzing the EP signals. An example analysis includes analyzing the EP signals of a perfused organoid where no CUT has been supplied to establish a baseline signal. This may be performed without a stimulus where the organoid naturally produces EP signals or with a stimulus, e.g., where the organoid produces EP signals in response to a stimulus. Another example analysis includes analyzing the EP signals over time to monitor the growth of the organoid, where more microelectrodes of the mesh MEA will provide measurable signals over time as the organoid grows over them. Another example analysis includes analyzing the EP signals after supplying a CUT and comparing the EP signals with the baseline. Another example analysis includes analyzing the EP signals after supplying a compound that produces a predictable response to determine. For the analysis, snippets of measured EP signals for a given time duration are graphically displayed via individual windows, each window corresponding to a microelectrode. The user would observe the snippets and analyze a portion of any EP signal determined to be of interest. By way of a non-limiting example, for a 60-microelectrode MEA, the display would include sixty windows, each corresponding to a microelectrode. Each window would display a snippet of the measured signal for the time duration of the window. For an hour-long study and a window time duration of one minute, the user would have to scroll through at least sixty sets of windows to observe the entirety of each of the measured EP signals. For longer studies, e.g., studies over a day, a month, a year, etc., the volume of the measured data (i.e., the EP signals) may be