Microfluidic-based electrospray source for analytical devices

• US 20060099116A1
• Filed: 12/13/2005
• Published: 05/11/2006
• Est. Priority Date: 10/13/2000
• Status: Active Grant

• Current Assignee: Fluidigm Corporation
• Original Assignee: Mycometrix Incorporated
• Inventors: Hao, Cunsheng Casey, Manger, Ian David, Unger, Marc Alexander
• Granted Patent: US 7,442,556 B2
• Time in Patent Office: Days
• US Class Current: 422/503
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 1/10 in the liquid or fluent state burettes, pipettes B01L3/02; sampling of ground water E02D1/06; metering by volume of fluids or fluent solid material G01F11/00, G01F13/00
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray
• CPC Class Codes: H01J 49/0018 Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
• CPC Class Codes: H01J 49/165 Electrospray ionisation
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials
• 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 436/2575 Volumetric liquid transfer

Abstract

This invention provides microfluidic devices and methods for using the same. Microfluidic devices of the present invention comprises a first elastic layer, a fluid flow channel within the elastic layer; and a means for providing a fluid sample from the fluid flow channel to an analytical device. The present invention also provides an analytical apparatus comprising such a microfluidic device and an analytical device.

Claims

1-59. -59. (canceled)

60. A method for providing a nanoliter volume of a fluid sample from a microfluidic device into an analytical device, the method comprising the steps of:

providing the analytical device;

providing the microfluidic device, wherein the microfluidic device comprises;

a first elastomeric layer having a fluid flow channel disposed therein,

a second elastomeric layer positioned in contact with the first elastomeric layer, wherein the second elastomeric layer has an integrated microfluidic pump disposed therein, and wherein the pump controls the flow of fluid through the fluid flow channel, and

a capillary having at least a portion fitted within the fluid flow channel, wherein the capillary comprises a nozzle, and wherein the capillary is interconnected to the analytical device for introducing the fluid sample from the fluid flow channel to the analytical device; and

injecting at least a portion of the fluid sample from the microfluidic device directly into the analytical device through the capillary nozzle.

61. The method of claim 60, wherein the microfluidic pump is a peristaltic pump.

62. The method of claim 60, wherein the fluid sample comprises a non-aqueous solvent.

63. The method of claim 60, wherein the capillary nozzle is an electrospray nozzle.

64. The method of claim 63, wherein the fluid sample injected into the analytical device through the capillary nozzle is converted into a mist while exiting the nozzle.

65. The method of claim 64, wherein the capillary nozzle is coupled to a device for applying a voltage to the capillary.

66. The method of claim 63, wherein the analytical device is an electrospray mass spectrometer.

67. The method of claim 60, wherein the analytical device is selected from the group consisting of UV spectrometers, fluorescence spectrometers, IR spectrometers, gas chromatographic devices, liquid chromatographic devices, NMR devices, mass spectrometers and combinations thereof.

68. The method of claim 60, wherein an electric field is not used to control the flow of fluid through the fluid flow channel of the microfluidic device.

69. The method of claim 60, wherein the fluid sample does not contain an ionic buffer to drive electroosmotic flow of the sample through the fluid flow channel.

70. A method for providing a nanoliter volume of a fluid sample from a microfluidic device into an analytical device, the method comprising the steps of:

providing the analytical device;

providing the microfluidic device, wherein the microfluidic device comprises;

a first elastomeric layer having a fluid flow channel disposed therein,

a second elastomeric layer having a pressure channel disposed therein, wherein the pressure channel controls the flow of fluid through said fluid flow channel, and

a capillary having at least a portion fitted within the fluid flow channel, wherein the capillary comprises a nozzle, and wherein the capillary is interconnected to the analytical device for introducing the fluid sample from the fluid flow channel to the analytical device; and

injecting at least a portion of the fluid sample from the microfluidic device to the analytical device through the capillary nozzle.

71. The method of claim 70, wherein the fluid sample comprises a non-aqueous solvent.

72. The method of claim 70, wherein the capillary nozzle is an electrospray nozzle.

73. The method of claim 70, wherein an electric field is not used to control the flow of fluid through the fluid flow channel of the microfluidic device.

74. The method of claim 70, wherein the fluid sample does not contain an ionic buffer to drive electroosmotic flow of the sample through the fluid flow channel.

75. A system to provide a nanoliter volume of a non-aqueous fluid sample from a microfluidic device to an analytical device, the system comprising:

an analytical device for analyzing at least a portion of the non-aqueous fluid sample; and

a microfluidic device for providing the at least portion of the fluid sample to the analytical device, wherein the microfluidic device comprises;

a first elastomeric layer having a fluid flow channel disposed therein,

a second elastomeric layer positioned in contact with the first elastomeric layer, wherein the second elastomeric layer has an integrated microfluidic pump disposed therein, and wherein the pump controls the flow of fluid through the fluid flow channel, and

a capillary having at least a portion fitted within the fluid flow channel, wherein the capillary comprises a nozzle, and wherein the capillary is interconnected to the analytical device for introducing the fluid sample from the fluid flow channel to the analytical device.

76. The system of claim 75, wherein the system further comprises a device for applying a voltage to the capillary to aerosolize the fluid sample exiting the capillary nozzle.

77. The system of claim 75, wherein the microfluidic device comprises a sample preparation chamber coupled to the fluid flow channel.

78. The system of claim 77, wherein the sample preparation chamber comprises a rotary fluid flow channel and a means for circulating a fluid within said rotary fluid flow channel for conducting a chemical reaction, an assay, or other sample preparations within said rotary fluid flow channel.

79. The system of claim 77, wherein the sample preparation chamber supplies an analyte to the non-aqueous fluid sample that is analyzed by the analytical device.

80. The system of claim 75, wherein the analytical device is a mass spectrometer.

81. The system of claim 80, wherein the mass spectrometer is an electrospray mass spectrometer.

82. A system to provide a nanoliter volume of a non-aqueous fluid sample from a microfluidic device to an analytical device, the system comprising:

an analytical device for analyzing at least a portion of the non-aqueous fluid sample; and

a microfluidic device for providing the at least portion of the fluid sample to the analytical device, wherein the microfluidic device comprises;

a first elastomeric layer having a fluid flow channel disposed therein,

a second elastomeric layer positioned in contact with the first elastomeric layer, wherein the second elastomeric layer has an integrated microfluidic pump disposed therein, and wherein the pump controls the flow of fluid through the fluid flow channel, and

a capillary having at least a portion fitted within the fluid flow channel, wherein the capillary comprises a nozzle, and wherein the capillary is interconnected to the analytical device for introducing the fluid sample from the fluid flow channel to the analytical device; and

a sample preparation chamber in fluid communication with the fluid flow channel of the microfluidic device, wherein the sample preparation chamber supplies an analyte to the non-aqueous fluid sample that is analyzed by the analytical device.

83. The system of claim 82, wherein the sample preparation chamber comprises a rotary fluid flow channel and a means for circulating fluid within said rotary fluid flow channel for conducting a chemical reaction, an assay, or other sample preparations within said rotary fluid flow channel.

84. The system of claim 83, wherein the means for circulating fluid comprises a pump and valve system for circulating the sample fluid within said rotary chamber.

85. The system of claim 83, wherein the means for circulating the fluid does not include applying an electric field to the fluid circulating in the rotary fluid flow channel.