Device for the study of living cells

• US 9,145,540 B1
• Filed: 02/25/2010
• Issued: 09/29/2015
• Est. Priority Date: 11/15/2007
• Status: Expired due to Fees

• Current Assignee: Seng Enterprises Limited
• Original Assignee: Seng Enterprises Limited
• Inventors: Deutsch, Mordechai, Deutsch, Assaf
• Primary Examiner(s): Bowers, Nathan
• Assistant Examiner(s): EDWARDS, LYDIA E
• Application Number:
  US12/712,232
• Time in Patent Office: 2,042 Days
• Field of Search: 4352831-3094
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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: C12M 23/10 Petri dish crystallising dishes B01L3/06
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 23/22 Transparent or translucent parts glassware for laboratory use B01L3/00
• CPC Class Codes: C12M 25/06 Plates; Walls; Drawers; Multilayer plates
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/40 : Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: G01N 1/312 : for samples mounted on planar substrates
• CPC Class Codes: G01N 15/01 : specially adapted for biological cells, e.g. blood cells investigating sedimentation of particle suspensions in blood G01N15/05
• CPC Class Codes: G01N 15/10 : Investigating individual particles
• CPC Class Codes: G01N 2015/1006 : for cytology
• CPC Class Codes: Y10T 156/1041 : Subsequent to lamination

Abstract

A device for performing a cell study. The device comprises a plate having a plurality of wells, each configured for containing aqueous solution and having a well bottom with a plurality of picowells and a plurality of biosensors each configured for measuring at least one cell characteristic while being in contact with the aqueous solution in a respective the well. The position of each the biosensor in a respective the well is limited by at least one pin.

Claims

1. A device for performing cell studies, comprising:

a plate having a plurality of wells, each configured for containing aqueous solution and having a well bottom including a plurality of picowells; and

a plurality of biosensors each disposed with at least a portion thereof in respective picowells and in contact with said aqueous solution therein;

wherein each biosensor is configured for measuring at least one cell characteristic while being in contact with said aqueous solution;

wherein a position of each biosensor relative to the at least one cell in its respective well bottom is limited by at least one pin.

2. The device of claim 1, wherein said at least one pin is attached substantially perpendicular to a respective well bottom.

3. The device of claim 1, wherein said at least one pin is attached substantially perpendicular to a front of a respective biosensor.

4. The device of claim 1, wherein said plurality of picowells are embossed on said well bottom.

5. The device of claim 1, further comprising a stamp having said plurality of picowells adhered on said well bottom.

6. The device of claim 1, wherein one or more picowell areas are inscribed between the pins.

7. The device of claim 1, wherein one or more picowell areas encircle at least 30% of the area covered by each pin.

8. A device according to claim 1, wherein said fluid control mechanism includes a capillary flow channel.

9. A device according to claim 8, wherein said capillary flow channel defines a substantially sealed waste reservoir.

10. A device according to claim 1, wherein said fluid control mechanism is further configured for providing aqueous solution to said plurality of wells.

11. A device according to claim 10, wherein said fluid control mechanism includes a fluid inlet area for drawing aqueous solution into said plurality of wells.

12. A device according to claim 1, further comprising a flow regulator configured to regulate a flow of the aqueous solution past said plurality of wells.

13. A device according to claim 1, wherein the position of each biosensor relative to the at least one cell in its respective well is limited to a fixed distance from said well bottom by said at least one pin.

14. A device according to claim 1, wherein said at least one pin is positioned substantially perpendicularly to the bottom of said well.

15. A device according to claim 1, wherein each of said biosensors is configured for measuring at least one of a cellular oxygen consumption and a proton excretion change of the at least one cell.

16. A method for embossing a plurality of picowells on a bottom of a well, comprising:

providing a plate having a plurality of wells each having a well bottom with at least one pin attached substantially perpendicular thereto;

providing a die having a negative geometry of a pattern comprising a plurality of picowells, wherein adjacent picowells are separated by a wall having a width that is less than 10% of a well diameter;

applying a curable material on at least one said well bottom; and

pressing said negative geometry toward said at least one said well bottom for curing said pattern in said curable material without bending said at least one pin.

17. The method of claim 16, wherein said die has at least one niche, configured for encircling a respective of said at least one pin during said embossing.

18. A device for performing a cell study, comprising:

a plate having a plurality of wells, each configured for containing aqueous solution and having a well bottom bearing a plurality of picowells;

a plurality of biosensors in contact with said aqueous solution in a respective well,

wherein each biosensor is configured for measuring at least one cell characteristic while being in contact with said aqueous solution; and

wherein said plurality of picowells are placed on said well bottom and configured for stabilizing cells during a movement of at least one of said plurality of biosensors

wherein a position of each said biosensor relative to the at least one cell in its respective well bottom is limited by at least one pin.