CN-122029270-A - On-chip brain design and architecture and method of use thereof

Abstract

The BoC includes one or more chambers for receiving neurons to be cultured, and one or more cell communication platforms disposed between at least a pair of the one or more chambers. The cell communication platform includes one or more features/structures configured, shaped, sized, and arranged to promote growth of axons of the neuronal population in a preferred direction and to block growth of axons in a direction opposite the preferred direction, thereby controlling at least one of directionality, transmissibility, and/or lateral diffusion between cultured neuronal populations. The cell communication platform establishes a neuronal circuit between the neuronal populations in each pair of chambers.

Inventors

• R. Renault
• P. Lack

Assignees

• 奥尔菲拉股份有限公司

Dates

Publication Date

20260512

Application Date

20241003

Priority Date

20231006

Claims (20)

1. 1. A brain on chip (BoC), comprising: One or more chambers for containing a population of neurons, and One or more cellular communication platforms located between at least a pair of the one or more chambers, wherein the one or more cellular communication platforms include one or more features/structures configured to promote the growth of axons of the neuron population in a preferred direction to culture a neuron circuit on the one or more cellular communication platforms between the neuron population in the at least a pair of chambers.
2. 2. The BoC of claim 1, wherein the one or more chambers are enclosed spaces formed by a base, a body, and one or more sidewalls of the BoC.
3. 3. The BoC of claim 2, wherein one or more sidewalls have an opening defined as: Allowing a population of neurons from at least one pair of chambers to expand through the opening to one or more cell communication platforms, and Preventing the neuronal population from moving.
4. 4. The BoC of claim 1, wherein the population of neurons in each of the one or more chambers is derived from a single neuron.
5. 5. The BoC of claim 1, wherein the population of neurons in each of the one or more chambers is heterogeneous.
6. 6. The BoC of claim 1, wherein the one or more chambers comprise one or more microwells connected thereto, the one or more microwells configured to provide a channel for adding, extracting, and/or replacing solution to the one or more chambers.
7. 7. The BoC of claim 6, wherein the solution is at least one of a cell culture medium or a chemical.
8. 8. The BoC of claim 1, wherein said one or more structures hinder or promote at least one of transitive, directional, or lateral diffusion of neuronal connections between a population of neurons in each pair of chambers of said one or more chambers in at least one direction.
9. 9. The BoC of claim 1, wherein said one or more structures are defined in an arrangement corresponding to at least one of a physiological structure or an anatomical structure of tissue.
10. 10. The BoC of claim 1, wherein the one or more structures is at least one of: one or more columns, or One or more of the structures of a polygon, Wherein the one or more pillars and/or the one or more polygonal structures are arranged to form a dwell region and one or more micro-channels, Wherein the dwell region is configured to inhibit growth of neurons/axons in the population of neurons in a first direction and/or redirect growth of neurons/axons to a second direction, and Wherein the one or more micro-channels are configured to promote growth of neurons/axons in a second direction.
11. 11. The BoC of claim 10, wherein the one or more columns have at least one of a triangular shape or a drop-shape.
12. 12. The BoC according to claim 10 wherein the one or more polygonal structures have a "C" -shaped profile.
13. 13. The BoC of claim 10, wherein the one or more structures further comprise at least one of: One or more irregularly shaped obstacles having curved grooves forming a first curved microchannel between the curved grooves and a first column having a water droplet shape, and/or A curved end at one end of the irregularly shaped obstacle, the curved end opposite the curved groove, the curved end forming a second curved microchannel between the curved end and a second post having a triangular shape.
14. 14. The BoC of claim 10, wherein one or more microchannels are defined as being diagonally oriented, linearly oriented, or curved oriented with respect to one or more cellular communication platforms.
15. 15. The BoC according to claim 1 wherein the one or more structures are protrusions extending from the body to a base of the BoC or are columnar structures defined between the body and the base by one or more cell communication platforms.
16. 16. The BoC of claim 1, wherein the population of neurons in a first chamber from the one or more chambers is sensory neuron cells and the population of neurons in a second chamber from the one or more chambers is readout cells, and wherein the one or more structures are configured to synaptically connect the sensory neuron cells in the first chamber with the readout cells in the second chamber via the one or more cell communication platforms.
17. 17. The BoC according to claim 16 wherein the neuronal circuit comprises a plurality of said readout cells connected to each sensory neuronal cell.
18. 18. The BoC according to claim 16 wherein the readout cells of the neuronal circuit strengthen the afferent synapses activated in a predefined and/or repeating temporal pattern and learn to respond preferentially to the predefined and/or repeating temporal pattern.
19. 19. The BoC of claim 16, wherein the sensory neuron cell is an olfactory receptor sensory neuron and the readout cell is an olfactory bulb neuron.
20. 20. A BoC platform comprising a neuronal circuit cultured by connecting one or more respective cellular communication platforms to a population of neurons in one or more chambers.

Description

On-chip brain design and architecture and method of use thereof Cross Reference to Related Applications The present application is a non-provisional application claiming priority to U.S. provisional patent application No. 63/542,889 filed ON 6 of 2023, 10, entitled "DESIGNSANDLAYOUTSFORBRAIN-ON-CHIPCOMPONENTSANDMETHODSFORMAKINGANDUSINGSAME," which is incorporated herein by reference in its entirety. Technical Field The present disclosure relates to the field of neural/neuronal circuits. More particularly, the present disclosure relates to a BoC having a cellular communication platform configured to facilitate formation/culture of neuronal circuits, and a method of making and using the same. Background A nerve/neuronal circuit is a population of neurons interconnected by synapses. Such circuits, whether naturally-occurring or artificially-cultured, perform a specific function when activated, as neurons are able to pass signals from one part of the circuit to another. The signals are transmitted by electrical signals or chemical processes. In a controlled environment, neurons can be cultured to form one or more neuronal circuits (sometimes referred to herein as "desired neuronal circuits"). For example, a population of neurons may be cultured in a petri dish. However, such solutions have limited control over the design of the formed neuronal circuit and are therefore not suitable for situations where a neuronal circuit that performs or simulates a specific function is required. For example, certain applications may require an operator to replicate naturally-occurring neuronal circuits, e.g., for experimental or research purposes, diagnosis of disease, determination of efficacy of different treatment regimens, etc. Some known solutions or BoC designs utilize circular obstacles or columnar structures to design the neuronal circuit. While these obstacles can create symmetrical junctions and extensive lateral diffusion between axons, they do not adequately guide the growth of the axonal edges of neurons in the desired direction. Thus, axons of one or both neuronal populations tend to become lost in the columnar structure array. The absence of axonal edge guidance limits transmissibility, especially where two neuronal populations are far apart, while also limiting the accuracy and fineness/complexity of constructing or replicating neuronal circuits. Other prior designs include lateral channels to guide the axons to the other side of the substrate or cavity to achieve transitivity. However, these structures introduce strong bias in the connections between the neuronal populations due to limited lateral diffusion. The lateral channels also do not reflect real world physiology or anatomy, and thus existing solutions do not accurately reflect or mimic naturally occurring neuronal circuits. Disclosure of Invention The present disclosure relates to a variety of BoC and/or BoC platforms, architectures, and designs configured to promote the growth of and axonal interconnection between two or more cultured neuron populations, and a method of culturing and using a neuron circuit with BoC. The BoCs, architectures, and designs disclosed herein are directed to guiding axon growth to establish connections between cultured neurons with or without lateral constraints, to facilitate asymmetry of the cultured neuron circuit, and/or to reproduce directionality, e.g., in a manner that mimics and/or reflects naturally occurring neuron circuits between two or more neurons that communicate with each other. The BoC includes one or more chambers for receiving cells/neurons to be cultured, and one or more cell communication platforms disposed between at least a pair of the one or more chambers. The cell communication platform comprises one or more features/structures configured (and shaped, sized, and/or arranged) to promote the growth of axons/neurons of the population of neurons in a preferred direction (and/or to block the growth of axons/neurons in a direction opposite to the preferred direction). The cell communication platform cultures neuronal circuits between the neuronal populations in at least one pair of chambers. The chambers may be enclosed spaces formed by the base, the body, and one or more sidewalls (e.g., gaps formed by cavities or protrusions in the body, the base, or the sidewalls when the body, the base, or the sidewalls are connected together). The sidewall may have an opening that may be defined (e.g., sized and/or shaped to be large enough) so that the neuron population in at least one pair of chambers can be amplified through the opening to the communication platform. The openings may be defined (e.g., sized and/or shaped to be small enough) to prevent movement of the neuron population (e.g., out of the chamber). These chambers can house a population of neurons. Sometimes, the population of neurons in each chamber may originate from a single neuron. Sometimes, the population of neurons in each chamber may be heterog