High-density ion transport measurement biochip devices and methods

• US 20060029955A1
• Filed: 07/05/2005
• Published: 02/09/2006
• Est. Priority Date: 03/24/2001
• Status: Abandoned Application

• Current Assignee: AVIVA Biosciences Corporation
• Original Assignee: AVIVA Biosciences Corporation
• Inventors: Wu, Lei, Xu, Jia, Guia, Antonio, Huang, Mingxian, Walker, George, Khachonesin, Sithiphong, Menikh, Abdelleh, Yuan, Julian
• Application Number:
  US11/175,789
• Publication Number:
  US 20060029955A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: B03C 5/026 using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
• CPC Class Codes: B65B 31/00 Packaging articles or materials under special atmospheric or gaseous conditions; Adding propellants to aerosol containers
• CPC Class Codes: C12Q 2565/629 being a microfluidic device
• CPC Class Codes: C23C 16/452 by activating reactive gas streams before their introduction into the reaction chamber, e.g. by ionisation or addition of reactive species
• CPC Class Codes: F16J 15/021 with elastic packing F16J15/08 takes precedence
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2333/705 : Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 31/22 : using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 33/48728 : Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: H01J 2237/3142 : Ion plating

Abstract

The present invention includes biochips for the measurement of cellular ion channels and methods of use and manufacture. The biochips of the present invention have enhanced sealing capabilities provided in part by chemically modifying the surface of the biochip surface or substrate or by exposure to an ionized gas. The present invention also includes novel cartridges for biochips.

Claims

10. An ion channel chip comprising:

a. a planar substrate;

b. at least one aperture positioned substantially perpendicular to said planar substrate;

c. a lipid positioned about said aperture, wherein a cell may continuously contact a portion of said lipid and said aperture.

1. An ion channel chip comprising:

a. a planar polymer plastic substrate treated with an ionized gas;

b. at least one aperture positioned substantially perpendicular to said planar polymer plastic substrate;

c. a gasket positioned about said aperture defining the perimeter of a chamber; and

wherein said treatment forms at least one functional group or moiety positioned sufficiently close to said aperture such that a cell can simultaneously contact said at least one functional group or moiety and said aperture.

2. The ion channel chip according to claim 1, wherein said polymer plastic is selected from the group consisting of a polyimide, a polyolefin and a polyacrylate.

3. The ion channel chip according to claim 1, wherein said polymer plastic is comprises a material selected from the group consisting of silicon, a wax, a paraffin wax, Parafilm(™

), and a fatty acid polymer.

4. The ion channel chip according to claim 1, wherein said substrate comprises a thickness between 5 mM and 300 mM.

5. The ion channel chip according to claim 1, wherein said ionized gas is a plasma gas.

6. The ion channel chip according to claim 1, wherein said at least one aperture has a diameter less than or equal to a diameter of a cell.

7. The ion channel chip according to claim 1, wherein said at least one aperture comprises at least 96 apertures or at least 1536 apertures.

8. The ion channel chip according to claim 1, wherein said functional group provides a negative charge or a hydrophilic property.

9. The ion channel chip according to claim 8, wherein said functional group comprises moiety selected from the group consisting of a sulfate, a phosphate, a borate, a silicate, a carboxyl, a thiosulfate, a thiophosphate and a thiocarbonate.

11. The ion channel chip according to claim 10, wherein said substrate comprises polymer plastic or glass.

12. The ion channel chip according to claim 10, wherein said lipid comprises a tail portion bound to said chip and a head portion capable of interacting with a cell.

13. The ion channel chip according to claim 10, wherein said lipid is a lipid bilayer comprising a first lipid layer and a second lipid layer, each lipid layer comprising a tail portion and a head portion, further wherein said first head portion is attached to a surface of said chip;

further wherein said first tail portion interacts with said second tail portion by van der Waals forces; and

further wherein said second head portion is capable of interacting with a cell.

14. The ion channel chip according to claim 13, wherein said lipid bilayer comprises phosphatidylethanolamine lipid.

15. The ion channel chip according to claim 10, wherein said lipid is in contact with the inner surface of said aperture.

16. A method of manufacturing a preassembled ion transport measurement cartridge comprising:

a. providing a cartridge and a chip substrate;

b. attaching said chip substrate to said cartridge;

c. drilling a throughbore through said chip substrate;

d. modifying the surface of said chip substrate;

wherein said modification increased the ability of said chip substrate to form a tight seal with a cell.

17. The method according to claim 15, wherein said modifying the surface comprises exposing said surface to an ionized gas.

19. A transportation system for an ion channel chip comprising:

a. a fluid tight container capable of accepting an ion;

b. an ion channel chip according to claim 1;

and

c. a fluid.

26. An automated system for processing of ion channel chips comprising:

a. a chip manipulating structure capable of engaging and manipulating the ion channel chip according to claim 1,

b. a negative pressure structure capable of providing negative pressure to said ion channel chip;

c. a positive pressure structure capable of providing positive pressure to said ion channel chip; and

d. a storage structure for storing said ion channel chip.

16-1. The method according to claim 15, wherein said modifying the surface comprises exposing said chip substrate to an acid or a base.

18. An ion channel chip comprising:

a. a planar polymer plastic substrate;

b. a glass surface layer positioned on opposing sides of said planar polymer plastic substrate; and

c. at least one aperture positioned perpendicular to said glass surface layers and said polymer plastic substrate.

20. A method of laser drilling an ion channel chip comprising:

a. providing a chip substrate;

wherein regions of said chip substrate not to be laser drilled are masked

b. providing a laser;

c. splitting the beam from said laser into two or more beamlets; and

d. focusing said beamlets through at least one lens onto said chip substrate thereby creating a throughbore or counterbore.

21. The method according to claim 20, wherein said masked regions are regions covered with a material selected from the group consisting of chrome coated quartz, aluminium coated quarz, dielectric coated quartz and metal.

22. The method according to claim 20, further comprising pretreating said chip substrate by exposing said chip substrate to a UV laser.

23. A method of manufacturing a substrate for an ion channel chip comprising:

a. treating a first glass surface with an acid;

b. treating a second glass surface with a base;

c. contacting said first glass surface with said second glass surface;

d. heating said surfaces to a temperature capable of bonding said first glass surface to said second glass surface.

24. A method of manufacturing a substrate for an ion channel chip comprising:

a. treating a first glass surface with a base;

b. treating a second glass surface with a base;

c. applying Na2SiO3 to said first glass surface;

d. contacting said second glass surface to said applied Na2SiO3; and

e. heading said surfaces to a temperature capable of bonding said Na2SiO3 to said glass surfaces.

25. A vacuum gasket for use with an ion channel chip comprising:

a. a planar surface having a length and width approximately equal to the length and width of at least one ion channel chip;

b. a sealing structure protruding parallel to said planar surface, wherein said sealing structure is capable of encircling the perimeter of an aperture of said ion channel chip when engaged;

c. a vacuum groove permitting the removal of air from between said planar surface and said chip thereby creating a vacuum seal; and

wherein said sealing structure defines a chamber when said gasket is sealed to said ion channel chip.

27. A storage structure for an ion channel chip comprising:

a. a top structure;

b. a bottom structure comprising a series of chip engaging structures, wherein each engaging structure is capable of engaging an ion channel chip;

further wherein said bottom structure reversible engages said top structure.