Multiple microchannels chip for biomolecule imaging, and method of use thereof

• US 6,587,197 B1
• Filed: 08/07/2000
• Issued: 07/01/2003
• Est. Priority Date: 12/06/1999
• Status: Expired due to Fees

• Current Assignee: Royce Technology Limited
• Original Assignee: Royce Technology Limited
• Inventors: Rahbar-Dehghan, Fariborz
• Primary Examiner(s): EVANS, FANNIE L
• Application Number:
  US09/634,709
• Time in Patent Office: 1,058 Days
• Field of Search: 356/318, 356/440, 356/246, 250/458.1, 250/459.1, 250/461.1, 250/461.2, 422/82.07, 422/82.08, 422/102, 422/942, 435/288.4, 435/288.7, 436/172
• US Class Current: 356/318
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides
• CPC Class Codes: G02B 21/361 Optical details, e.g. image relay to the camera or image sensor G02B21/364 takes precedence; illumination details G02B21/06 and subgroups
• CPC Class Codes: Y10S 977/704 Nucleic acids, e.g. DNA or RNA

Abstract

A panel chip for supporting biological samples for observation with a microscope. The glass panel defines a top flat surface, a bottom bearing surface, and at least a few channels extending generally parallel to each other from top to bottom surfaces. Each of the channels defines a top access mouth for ingress of biological samples, wherein each channel is obliquely inclined so as to make a significant acute angle relative to an axis perpendicular to said top flat surface, in order to facilitate the guidance of maximum light into the channel due to zero loss of reflection and to produce the maximum number of total internal reflection and to guide the maximum light out of the microchannel in such a manner that produces no artifact halo for maximum detection and sensitivity. Each channel has such an inner diameter as to accommodate flow through viscosity of a biological sample containing fluid.

Claims

1. A rigid panel chip for supporting biological samples for observation with a microscope, said rigid panel chip comprising a rigid panel defining a top flat surface, a bottom bearing surface, and at least a few channels extending generally parallel to each other from said top to bottom surfaces, each of said channels defining a top access mouth for ingress of said biological samples, wherein each of said channel is obliquely inclined so as to make an acute angle relative to an axis perpendicular to said top flat surface, and each said channel having such an inner diameter as to accommodate flow through viscosity of a biological sample containing fluid.

2. A panel chip as in claim 1, wherein said channels are cylindroid and disposed in an array selected from the group consisting of circular and conical arrays.

3. A panel chip as in claim 2, wherein said cylindroid channels have a constant diameter ranging between 10 to 500 micrometers.

4. A panel chip as in claim 3, wherein said channels diameter range between 50 to 200 micrometers.

5. A panel chip as in claim 4, wherein said channels diameter is of about 100 micrometers.

6. A panel chip as in claim 3, wherein said acute angle ranges between 30 to 60 degrees.

7. A panel chip as in claim 6, wherein said acute angle is of approximately 42 degrees.

8. A panel chip as in claim 4, wherein said acute angle ranges between 30 to 60 degrees.

9. A panel chip as in claim 8, wherein said acute angle is of approximately 42 degrees.

10. A panel chip as in claim 4, wherein the number of said channels is about two to tens of thousands, extending through the thickness of said rigid panel.

11. A panel chip as in claim 3, made from a material selected from the group consisting of:

glass, quartz, polypropylene, polyolefin, nylon, and fused silica.

12. A panel chip as in claim 11, wherein said panel chip is made of transparent glass.

13. A glass panel as in claim 12, having a thickness ranging between about 0.5 to 5 millimeters.

14. A panel chip as defined in claim 1,

wherein each of said channels is lined with an inner coating made from a light reflecting metallic material.

15. A panel chip as defined in claim 14,

wherein said channel inner coating material is a metallic material selected from the group comprising aluminum and silver.

16. A panel chip as defined in claim 15, wherein said channel has a deposit of protective monolayer made from a material selected from the group consisting of silicon or magnesium fluoride.

17. A method of observation by flat surface laser scanner of biological samples in a glass panel, the glass panel of the type defining a top flat surface, a bottom bearing surface, and a plurality of channels extending generally parallel to each other from said top to bottom surfaces and each defining a top access mouth for the biological sample, the method including the following steps:

a) Inclining the channels in an oblique fashion so as to make a significant acute angle relative to an axis perpendicular to the top flat surface of the glass panel,

b) Enlarging the inner diameter of each said channel enough as to accommodate power assisted flow through viscosity of a biological sample containing fluid;

c) Providing fluorescein dyes inside the biological sample containing fluid;

d) Directing a coherent laser beam transversely through a selected channel top access mouth and coaxially into the corresponding channel, so as to excite the fluorescein dyes, wherein an optically apparent glow is generated by the excited dyes without a halo being generated about the top access mouth;

e) Allowing sufficient time for the fluorescein dyes to project the optically apparent glow upwardly beyond said channel top access mouth; and

f) Performing optical measurements of this upward out of channel projecting fluorescein glow to generate evidence data on the chemical properties and location of the biological samples.

18. A method as defined in claim 17, wherein said power assisted flow through of biological sample, is selected from the group consisting of low vacuum assist, and centrifugal force.

19. A method of observation by flat surface laser scanner of biological samples in a glass panel, the glass panel of the type defining a top flat surface, a bottom bearing surface, and a plurality of channels extending generally parallel to each other from said top to bottom surfaces and each defining a top access mouth for the biological sample, the method including the following steps:

a) Inclining the channels in an oblique fashion so as to make a significant acute angle relative to an axis perpendicular to the top flat surface of the glass panel,

b) Enlarging the inner diameter of each said channel enough as to accommodate power assisted flow through viscosity of a biological sample containing fluid;

c) Directing a coherent laser beam transversely through a selected channel top access mouth and coaxially into the corresponding channel;

d) Measuring deterioration of light intensity upon the binding of biomolecules to the channels inner wall; and

e) Performing analysis of this light intensity deterioration to generate evidence data on the chemical properties and location of the biological samples.

20. A method of observation as in claim 19,

for further including a step (c1) intervening between said steps c) and d), wherein said step (c1) reads as follows:

c1) Measuring deterioration of light intensity upon the binding of tagged gold particles to the channels.