High throughput screen

• US 10,006,902 B2
• Filed: 06/23/2014
• Issued: 06/26/2018
• Est. Priority Date: 06/12/1998
• Status: Expired due to Fees

• Current Assignee: Sophion Bioscience A/S
• Original Assignee: Sophion Bioscience A/S
• Inventors: Owen, David Geraint, Byrne, Nicholas Gerard
• Primary Examiner(s): Brown, Melanie Yu
• Application Number:
  US14/311,607
• Publication Number:
  US 20150068925A1
• Time in Patent Office: 1,464 Days
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 27/28 Electrolytic cell components
• 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 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

The present invention relates to a structure comprising a biological membrane and a porous or perforated substrate, a biological membrane, a substrate, a high throughput screen, methods for production of the structure membrane and substrate, and a method for screening a large number of test compounds in a short period. More particularly it relates to a structure comprising a biological membrane adhered to a porous or perforated substrate, a biological membrane capable of adhering with high resistance seals to a substrate such as perforated glass and the ability to form sheets having predominantly an ion channel or transporter of interest, a high throughput screen for determining the effect of test compounds on ion channel or transporter activity, methods for manufacture of the structure, membrane and substrate, and a method for monitoring ion channel or transporter activity in a membrane.

Claims

1. A method of manufacturing a structure for screening for the detection or assay of compounds with activity on ion channels or transporters, comprising:

selecting a substrate;

perforating the substrate with plural pores having a diameter between 0.5 μ

m and 10 μ

m;

smoothing the pore edges;

positioning said substrate along a bottom of a multi-well plate forming a bottom wall thereof with at least one pore disposed in each well.

2. The method of claim 1, wherein said selecting comprises selecting a material from a group which comprises glass, plastics, rubber, polytetraflurotethylene (PTFE), PTFE/glass fabric and polyethylene terephthalate (PETP).

3. The method of claim 1, wherein said perforating comprises one of laser forming, photo-etching, casting and physical piercing.

4. The method of claim 3, wherein said laser forming comprises computer controlled forming of a grid of pores on said substrate with plural pores in each said well.

5. The method of claim 3, further comprising, subsequent to said perforating, exposing the substrate to a localized heat or electrical plasma to increase the smoothness of the pores.