Bio-assessment device and method of making the device

Patent metadata

Field	Value
Publication number	US-10634665-B2
Application number	US-201515513949-A
Country	US
Kind code	B2
Filing date	Sep 24, 2015
Priority date	Sep 24, 2014
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Disclosed herein are embodiments of a device that can be used to mimic the biochemical and physiological actions of a lung organ. Also disclosed herein are embodiments of components that are included in the device as well as methods of making and using the device. Further disclosed are platform device embodiments and various components used therein that can be used in combination with the lung organ devices disclosed herein. In some embodiments, the disclosed devices can be used to determine drug toxicity and also can be used with one or more disease models to determine methods of treating disease.

First claim

We claim:

1. A device, comprising:
a first component comprising (i) a first substrate comprising a first plurality of channels, a first inlet, a second inlet, a first outlet fluidly coupled to the first inlet, a second outlet fluidly coupled to the second inlet, and at least two fluid ports, wherein the first plurality of channels are fluidly coupled to the first inlet and to one of the at least two fluid ports; (ii) a second substrate comprising a second plurality of channels, a first fluid port fluidly coupled to the first inlet of the first substrate through at least one fluid port of the first substrate, and a second fluid port fluidly coupled to the second inlet of the first substrate, wherein the plurality of channels are fluidly coupled to the second fluid port; and wherein the first plurality of channels and the second plurality of channels are fluidly coupled and wherein the first inlet and the second inlet of the first substrate are positioned adjacent to one another at the same end of the substrate; and (iii) a bronchiolar membrane comprising a first surface and a second surface, wherein the bronchiolar membrane is positioned between the first substrate and the second substrate such that the first surface of the bronchiolar membrane touches the first substrate and the second surface of the bronchiolar membrane touches the second substrate and wherein the first plurality of channels are arranged in a branching configuration and the second plurality of channels are arranged in a branching configuration that matches that of the first plurality of channels so as to provide two sets of branched channels that have the same branching configuration and that extend along the bronchiolar membrane in a direction parallel to the first and second surfaces of the bronchiolar membrane and wherein each of the first and second plurality of channels are continuously open to the bronchiolar membrane along a length of the first and second plurality of channels so as to provide fluid communication between the bronchiolar membrane and the first and second plurality of channels; and
a second component, comprising an alveolar membrane component comprising an alveolar membrane material coupled to a substrate comprising a plurality of apertures; and

wherein the first component and the second component are fluidly coupled together without any intervening connecting tubes providing the fluid coupling between the first component and the second component.

2. The device of claim 1 , wherein the second substrate further comprises:
a third fluid port fluidly coupled to the first outlet of the first substrate; and
a fourth fluid port fluidly coupled to the second outlet of the first substrate.

3. The device of claim 1 , wherein the second component further comprises:
a fluid-compatible component comprising:
a plurality of substrates coupled together,
a first fluid inlet fluidly coupled to the first inlet of the first substrate of the first component, and
a first fluid outlet fluidly coupled to the first outlet of the first substrate of the first component; and

a medium-compatible component comprising:
a plurality of substrates coupled together,
a second fluid inlet fluidly coupled to the second inlet of the first substrate of the first component, and
a second fluid outlet fluidly coupled to the second outlet of the first substrate of the first component; and

wherein the alveolar membrane component is positioned between and fluidly coupled to the fluid-compatible component and the medium-compatible component.

4. The device of claim 1 , wherein the first substrate is positioned on top of the bronchiolar membrane and the second substrate is placed below the bronchiolar membrane.

5. The device of claim 1 , wherein the bronchiolar membrane comprises a porous material.

6. The device of claim 1 , wherein the bronchiolar membrane comprises poly-L-lactic acid.

7. The device of claim 1 , wherein the bronchiolar membrane comprises an endothelial side that is or can be associated with endothelial cells comprising lung microvascular endothelial cells selected from HLMVE cells and an epithelial side that is or can be associated with epithelial cells selected from BEAS-2B bronchial epithelial cells.

8. The device of claim 1 , wherein the bronchiolar membrane includes a plurality of fluid ports that align with one or more of the at least two fluid ports of the first substrate of the first component.

9. The device of claim 3 , wherein the plurality of substrates of the fluid-compatible component and the medium-compatible component comprises substrates comprising one or more microchannels or nanochannels.

10. The device of claim 1 , wherein the alveolar membrane material of the alveolar membrane component is selected to resiliently deform and reform and to allow gas exchange between the fluid-compatible component and the medium-compatible component.

11. The device of claim 3 , wherein one side of the membrane material of the alveolar membrane component is associated with a first population of cells comprising immune responsive cells, surfactant-producing cells, or a combination thereof and the other side of the membrane material is associated with a second population of cells comprising pulmonary microvascular cells and wherein the first population of cells is associated with a side of the membrane material of the alveolar membrane component that is fluidly coupled with the fluid-compatible component and the second population of cells is associated with a side of the membrane material of the alveolar membrane component that is fluidly coupled with the medium-compatible component.

12. The device of claim 11 , wherein the first population of cells comprises AT1 cells, AT2 cells, or a combination thereof and wherein the second population of cells comprises human lung microvascular endothelial cells, human lung smooth muscle cells, human lung fibroblast cells, monocytes, dendritic cells, or a combination thereof.

13. The device of claim 1 , wherein the first component is fluidly coupled to a plurality of second components and the device further comprises a fluid management device fluidly coupled to the device.

14. A method, comprising:
introducing a compound, or composition containing a compound, into the device according to claim 1 ; and
analyzing a response generated by the device or the platform device after the compound, or composition thereof, has been introduced into the device or the platform device.

15. The method of claim 14 , wherein analyzing the response generated by the device comprises detecting an immune response produced by one or more cell populations associated with the bronchiolar membrane of the device.

16. The method of claim 14 , further comprising extracting from the device a sample selected from a fluid that passes through the device, a cell sample, a tissue sample, or a combination thereof to determine the presence or amount of at least one compound.

17. The method of claim 14 , wherein the method further comprises introducing the sample into a chromatograph, a mass spectrometer, or a combination thereof to detect the compound.

Assignees

• Triad Nat Security Llc
• Univ Vanderbilt

Inventors

• Iyer Rashi
• Huang Jen-Huang
• Nath Pulak
• Harris Jennifer
• Wikswo Jr John P

Classifications

• G01N33/5014

  for testing toxicity · CPC title

• B01L3/502738

  characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746) · CPC title

• B01L2200/027

  for microfluidic devices · CPC title

• F16K7/045

  by electric or magnetic means · CPC title

• B01L2300/123

  Flexible; Elastomeric · CPC title