Modular apparatus for chemical microanalysis

• US 6,759,013 B2
• Filed: 09/17/1998
• Issued: 07/06/2004
• Est. Priority Date: 09/17/1998
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: van de Goor, Tom A., Kaltenbach, Patrick
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SINES, BRIAN J
• Application Number:
  US09/156,804
• Publication Number:
  US 20010008613A1
• Time in Patent Office: 2,119 Days
• Field of Search: 422/68.1, 422/99, 422/100, 422/101, 422/102, 422/103, 422/104, 422/198, 204/193, 204/194, 204/403.01, 204/403.03, 204/409, 204/164, 204/450, 204/451, 204/416, 204/418, 204/419, 204/452, 204/453, 204/601, 204/604, 436/174, 436/177, 436/178, 436/180
• US Class Current: 422/504
• CPC Class Codes: G01N 2030/8881 Modular construction, specially adapted therefor
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A modular microchannel apparatus for analysis of an analyte. The apparatus includes a separation unit and a reservoir unit. The separation unit has a microchannel. The analyte can be driven to pass through the microchannel such that the time for the analyte to pass through the microchannel is indicative of the molecular characteristics of the analyte. The reservoir unit has one or more reservoirs for coupling operatively modularly with the separation unit to supply liquid reagents to the separation unit. The reservoirs has prepackaged liquid reagents in it before the reservoir unit is coupled with the separation unit.

Claims

1. A modular microchannel apparatus for the chemical analysis of an analyte in a sample, comprising:

(a) a plurality of separation units each effective to carry out a different analytical application of interest and comprised of a first solid substrate having a microchannel present in a surface thereof, wherein the microchannel in each separation unit is of a different length corresponding to the analytical application of interest for the separation unit containing the microchannel and forms a separation column or capillary that separates the analyte from the sample according to the molecular characteristics of the analyte;

(b) a single reservoir unit in the form of a plate comprised of a reservoir that contains a liquid for introduction into each of the microchannels of the separation units in succession; and

(c) an external power source capable of generating an electric field difference between electrically conductive probes extending into the reservoir unit, the power source operatively connected to the reservoir unit for electrokinetically driving the liquid from the reservoir through the microchannels of the separation units,

wherein the reservoir unit has dimensions that enable the operative and modular coupling of the reservoir unit to each separation unit in succession to allow liquid from the reservoir to be electrokinetically driven, by a power-source-generated electric field difference between the probes, into the microchannel of the separation unit that is operatively and modularly coupled to the reservoir unit, and

at least one of the separation units is chip-shaped and further comprised of a second substrate having a surface facing and joining the first substrate surface, thereby forming the microchannel.

2. An apparatus according to claim 1, wherein the first and second substrates serve as first and second halves, respectively, of the at least one separation unit, and the facing and joining substrate surfaces are substantially planar.

3. An apparatus according to claim 1, wherein at least one of the separation units has one or more openings leading to the microchannel capable of admitting liquid reagents such that when the separation unit and the reservoir unit are operatively and modularly coupled, the openings are aligned with the reservoirs thereby allowing the liquid reagents and the analyte to pass from the reservoirs into the microchannel without substantial leakage.

4. An apparatus according to claim 2, wherein at least one of the separation units includes a substrate comprised of a material other than silicon or silicon dioxide in which the first microchannel is formed by laser ablation.

5. An apparatus according to claim 2, wherein the reservoir unit includes a membrane that covers at least one of the reservoirs confining the prepackaged liquid reagent therein, wherein the membrane is penetrable with a probe for applying a driving force to drive movement of liquid reagent and analyte from the reservoir through the microchannel of at least one of the separation units.

6. An apparatus according to claim 2, wherein both substantially planar surfaces of the separation unit having a first half and a second half have a laser-ablated channel thereon and the two channels join to form the microchannel.

7. An apparatus according to claim 2, wherein the channel of at least one separation unit is formed by laser ablation.

8. An apparatus according to claim 2, wherein the external power unit comprises a powering plate operatively and modularly coupled to the reservoir unit, the powering plate having an electrical connection to the reservoir to provide a driving force to drive movement of the liquid reagents and analyte from the reservoir through the microchannel.

9. The apparatus according to claim 2, further comprising a support plate for operatively and modularly coupling to the separation units.

10. An apparatus according to claim 9, further comprising a peltier plate operatively and modularly coupled to the support plate for controlling the temperature of at least one of the separation units.

11. An apparatus according of claim 10, wherein the pettier plate can be used to heat or cool at least one of the separation units by selecting an appropriate mode of operation.

12. An apparatus according to claim 11, further comprising a heat exchanger operatively connected to the peltier plate to transfer heat between the peltier plate and the surrounding environment.

13. A kit for making a modular microchannel apparatus for the chemical analysis of an analyte in a sample, comprising:

(a) a plurality of separation units each effective to carry out a different analytical application of interest and comprised of a first solid substrate having a microchannel present in a surface thereof, wherein the microchannel in each separation unit is of a different length corresponding to the analytical application of interest for the separation unit containing the microchannel and forms a separation column or capillary that separates the analyte from the sample according to the molecular characteristics of the analyte;

(b) a single reservoir unit in the form of a plate comprised of a reservoir that contains a liquid for introduction into each of the microchannels of the separation units in succession; and

(c) an external power source capable of generating an electric field difference between electrically conductive probes and having dimensions that enable its modular and operative connection to the reservoir unit for electrokinetically driving the liquid from the reservoir through the microchannels of the separation units,

wherein the reservoir unit has dimensions that enable the operative and modular coupling of the reservoir unit to each separation unit in succession,

the probes extend into the reservoir unit when the reservoir unit is operatively coupled to the external power source,

a power-source-generated electric field difference between the probes electrokinetically drives liquid from the reservoir into the microchannel of the separation unit that is operatively and modularly coupled to the reservoir unit, and

at least one of the separation units is chip-shaped and further comprised of a second substrate having a surface facing and joining the first substrate surface, thereby forming the microchannel.

14. A modular microdevice for analyte analysis, comprising:

(a) a plurality of separation units each effective to carry out a different analytical application of interest and comprised of a solid substrate having a micro channel present in a surface thereof, wherein the microchannel in each separation unit is of a different length corresponding to the analytical application of interest for the separation unit containing the microchannel and forms a separation column or capillary that separates an analyte from a sample according to the molecular characteristics of the analyte;

(b) a single reservoir unit in the form of a plate comprised of a plurality of reservoirs, wherein each reservoir contains a liquid, each liquid is suitable for introduction into a microchannel of a separation unit; and

(c) an external power source capable of generating an electric field difference between electrically conductive probes extending into the reservoir unit, the power source operatively connected to the reservoir unit for electrokinetically driving liquids from the reservoir unit through the microchannels of the separation units,

wherein the reservoir unit has dimensions that enable the operative and modular coupling of the reservoir unit to each separation unit in succession to allow liquid from at least one of the plurality of reservoirs to be electrokinetically driven, by a power-source-generated electric field difference between the probes, into the microchannel of the separation unit that is operatively and modularly coupled to the reservoir unit, and

at least one of the separation units is chip-shaped and further comprised of a second substrate having a surface facing and joining the first substrate surface, thereby forming the microchannel.

15. The modular microchannel apparatus system of claim 14, wherein each of two separation units of the plurality has a microchannel of a different size.