Basal Ganglia-On-Chip For Screening Therapeutic Agents For Brain And Nervous System Diseases

Patent metadata

Field	Value
Publication number	US-2019369089-A1
Application number	US-201916426795-A
Country	US
Kind code	A1
Filing date	May 30, 2019
Priority date	May 31, 2018
Publication date	Dec 5, 2019
Grant date	—

Abstract

The present disclosure provides a basal ganglia-on-a-chip for screening therapeutic agents for brain and nervous system diseases and a method for fabricating the same. The present invention provides a method for screening therapeutic agents for dopamine-dependent brain and nervous system diseases by using a basal ganglia-on-a-chip. When the basal ganglia-on-a-chip of the present invention is used in the effect evaluation of therapeutic agents for brain and nervous system diseases, the effect evaluation of therapeutic candidate substances can be economically and promptly carried out compared with an existing technique.

First claim

What is claimed is:

1 . A basal ganglia-on-a-chip for screening therapeutic agents for brain and nervous system diseases, the basal ganglia-on-a-chip comprising:
(a) graphene-conjugated magnetic nanoparticles patterned on a substrate; (b) (i) a first hydrogel containing glutamatergic neurons and (ii) a second hydrogel containing GABAergic neurons, the first and second hydrogels being disposed in parallel on a pattern of the graphene-conjugated magnetic nanoparticles; (c) a third hydrogel in contact with the second hydrogel, the third hydrogel containing GABAergic neurons and neuronal membrane protein-specific antibody-conjugated magnetic nanoparticles; and (d) a fourth hydrogel in contact with the third hydrogel, the fourth hydrogel containing dopaminergic neurons and neuronal membrane protein-specific antibody-conjugated magnetic nanoparticles.

2 . The basal ganglia-on-a-chip of claim 1 , wherein the brain and nervous system diseases are dopamine-dependent brain and nervous system diseases.

3 . The basal ganglia-on-a-chip of claim 2 , wherein dopamine-dependent brain and nervous system disease are brain and nervous system disease selected from the group consisting of Parkinson's disease, neurocognitive disorder, attention deficit hyperactivity disorder, restless leg syndrome, schizophrenia, and anxiety.

4 . The basal ganglia-on-a-chip of claim 1 , wherein the first hydrogel to the fourth hydrogel contain at least one hydrogel monomer selected from the group consisting of gelatin methacrylate (GeIMA), acrylic acid, acrylamide, N-isopropylacrylamide (NIPAAM), and polyethylene glycol diacrylate (PEGDA).

5 . The basal ganglia-on-a-chip of claim 1 , wherein the first hydrogel to the fourth hydrogel further contain decellularized brain matrix (DECM).

6 . The basal ganglia-on-a-chip of claim 1 , wherein in the graphene-conjugated magnetic nanoparticles, a modified amine group on a surface of the magnetic nanoparticle is combined with a carboxyl group of a graphene oxide.

7 . The basal ganglia-on-a-chip of claim 1 , wherein an antibody specific to cell membrane proteins bound to the neuronal membrane protein-specific antibody-conjugated magnetic nanoparticles is an antibody specific to membrane receptors, transport proteins, membrane enzymes, or cell adhesion molecules in neurons.

8 . A method for screening therapeutic agents for brain and nervous system diseases by using a basal ganglia-on-a-chip, the method comprising:
(a) treating dopaminergic neurons with a candidate of therapeutic agents for brain and nervous system diseases; and (b) investigating whether the dopaminergic neurons proliferate or are reduced.

9 . The method of claim 8 , wherein the dopaminergic neurons are induced to have damages.

10 . The method of claim 9 , wherein the damages are caused by oxidative stress.

11 . The method of claim 8 , wherein the dopaminergic neurons are induced to differentiate.

12 . A method for fabricating a basal ganglia-on-a-chip for screening therapeutic agents for brain and nervous system diseases, the method comprising:
(a) patterning graphene-conjugated magnetic nanoparticles on a substrate while a magnetic field is applied to the substrate in a vertical direction; (b) printing a first bio-ink on a pattern of the graphene-conjugated magnetic nanoparticles while a magnetic field is applied to the pattern in a vertical direction, the first bio-ink containing glutamatergic neurons and a hydrogel; (c) printing a second bio-ink on the pattern of the graphene-conjugated magnetic nanoparticles while a magnetic field is applied to the pattern in a vertical direction, such that the second bio-ink is adjacent to one side surface of a region printed with the first bio-ink, the second bio-ink containing GABAergic neurons and a hydrogel; (d) printing a third bio-ink on a region printed with the second bio ink in step (c), the third bio-ink containing GABAergic neurons, neuronal membrane protein-specific antibody-conjugated magnetic nanoparticles, and a hydrogel; (d) printing a fourth bio-ink on a region printed with the third bio-ink in step (d), the fourth bio-ink containing dopaminergic neurons, neuronal membrane protein-specific antibody-conjugated magnetic nanoparticles, and a hydrogel; and (f) applying a magnetic field in a vertical direction from below the substrate.

Assignees

• Univ Sogang Res Foundation

Inventors

• Choi Jeong-Woo
• Lee Won Jun
• Shin Jae Wook

Classifications

• B33Y10/00

  Processes of additive manufacturing · CPC title

• B33Y80/00

  Products made by additive manufacturing · CPC title

• G01N33/5058 Primary

  Neurological cells · CPC title

• G01N2800/2814

  Dementia; Cognitive disorders · CPC title

• G01N2800/302

  Schizophrenia · CPC title