Ultra high throughput microfluidic analytical systems and methods
First Claim
1. An illumination and detection system for use in illuminating a plurality of samples in a plurality of microchannels located in a detection region on a microfluidic device, and for detecting radiation emitted from the detection region, wherein the microchannels are substantially parallel along a first direction within the detection region, the system comprising:
- an illumination source for providing an excitation beam having two or more excitation wavelengths;
focussing optics for focussing the excitation beam onto a first plane defined by the plurality of microchannels in the detection region such that the focussed excitation beam is elongated, having a major axis substantially perpendicular to the first direction, wherein the excitation beam impinges upon the detection region at a non-normal angle of incidence relative to the first plane, and wherein the excitation beam simultaneously excites the samples in at least two of the microchannels so as to cause the excited samples to emit radiation;
two or more detectors, wherein each detector detects a specific range of radiation wavelengths; and
detection optics for directing radiation from the samples toward the detectors such that the wavelengths of the emitted radiation within each specific radiation wavelength range are directed toward the corresponding detector.
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Accused Products
Abstract
Analytical systems and methods that use a modular interface structure for providing an interface between a sample substrate and an analytical unit, where the analytical unit typically has a particular interface arrangement for implementing various analytical and control functions. Using a number of variants for each module of the modular interface structure advantageously provides cost effective and efficient ways to perform numerous tests using a particular substrate or class of substrates with a particular analytical and control systems interface arrangement. Improved optical illumination and detection system for simultaneously analyzing reactions or conditions in multiple parallel microchannels are also provided. Increased throughput and improved emissions detection is provided by the present invention by simultaneously illuminating multiple parallel microchannels at a non-normal incidence using an excitation beam including multiple excitation frequencies, and simultaneously detecting emissions from the substances in the microchannels in a direction normal to the substrate using a detection module with multiple detectors.
38 Citations
75 Claims
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1. An illumination and detection system for use in illuminating a plurality of samples in a plurality of microchannels located in a detection region on a microfluidic device, and for detecting radiation emitted from the detection region, wherein the microchannels are substantially parallel along a first direction within the detection region, the system comprising:
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an illumination source for providing an excitation beam having two or more excitation wavelengths;
focussing optics for focussing the excitation beam onto a first plane defined by the plurality of microchannels in the detection region such that the focussed excitation beam is elongated, having a major axis substantially perpendicular to the first direction, wherein the excitation beam impinges upon the detection region at a non-normal angle of incidence relative to the first plane, and wherein the excitation beam simultaneously excites the samples in at least two of the microchannels so as to cause the excited samples to emit radiation;
two or more detectors, wherein each detector detects a specific range of radiation wavelengths; and
detection optics for directing radiation from the samples toward the detectors such that the wavelengths of the emitted radiation within each specific radiation wavelength range are directed toward the corresponding detector. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 67)
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15. A method of simultaneously analyzing a plurality of samples in a plurality of microchannels on a microfluidic device, wherein the plurality of microchannels are substantially parallel along a first direction within a detection region on the microfluidic device, the method comprising the steps of:
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simultaneously exciting the samples in at least two of the microchannels in the detection region by focussing an excitation beam having two or more excitation wavelengths onto a first plane defined by the plurality of microchannels in the detection region such that the focussed excitation beam is elongated, having a major axis substantially perpendicular to the first direction, wherein the excitation beam impinges upon the detection region at a non-normal angle of incidence relative to the first plane, and wherein the excited samples emit radiation; and
simultaneously detecting the radiation emitted by the two or more excited samples using two or more detectors, wherein each of the detectors detects a specific range of radiation wavelengths. - View Dependent Claims (16, 17, 18, 19, 20)
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21. A microfluidic device comprising:
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a fluid reservoir for holding a conducting fluid;
a conducting capillary for supplying the fluid to the reservoir, wherein one end of the capillary is positioned at a first location in the reservoir;
a voltage source having a first terminal and a second terminal;
a first lead connecting the first terminal to the conducting capillary; and
a second lead connecting the second terminal to a second location in the reservoir;
wherein when the level of the fluid within the reservoir is at least at the first location, an electric current is present between the first and second terminals, and wherein when the fluid level is below the first location such that there is no contact between the fluid and the capillary, no electric current between the first and second terminals is present. - View Dependent Claims (22, 23, 24, 25)
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26. A microfluidic device comprising:
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a fluid reservoir for holding a conducting fluid;
a conducting capillary for supplying the fluid to the reservoir, wherein one end of the capillary is positioned at a first level within the reservoir;
a voltage source having a first terminal and a second terminal;
a first lead connecting the first terminal to the conducting capillary;
a second lead connecting the second terminal to a location at a second level within the reservoir, wherein the second level is below the first level; and
a fluid monitoring element for providing fluid to the reservoir from a fluid source;
wherein an electric current is present between the first and second terminals only when the level of fluid in the reservoir is at least at the level associated with the first location, and wherein the fluid monitoring device provides fluid to the reservoir through the capillary when no current is present. - View Dependent Claims (27, 28)
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29. A method of automatically refilling a fluid reservoir in a microfluidic device, wherein the device includes a conducting capillary and a voltage supply, wherein a first end of the capillary is positioned at a first level within the reservoir, wherein a first terminal of the voltage supply is connected to the capillary and wherein a second terminal of the voltage supply is connected to a location at a second level within the reservoir, the second level being below the first level, the method comprising the steps of:
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detecting an absence of electric current between the first and second terminals through the capillary, wherein no electric current flows between the first and second terminals when the fluid level is below the first level in the reservoir; and
automatically supplying fluid to the reservoir through the capillary using a fluid monitoring device in response to the absence of current so as to raise the fluid level. - View Dependent Claims (30, 31)
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32. An analytical system comprising:
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a sample substrate having a plurality of substrate reservoirs and a plurality of microchannels disposed thereon, wherein the plurality of microchannels connects the plurality of substrate reservoirs, and wherein two or more of the microchannels are substantially parallel in a detection region on the substrate; and
a modular interface, having two or more removably attachable interface modules, for interfacing with a plurality of instrument connectors, the interface including;
a substrate interface module having at least one fluid reservoir disposed therein, wherein the substrate interface module is removably attached to the substrate, and wherein the at least one fluid reservoir is positioned so as to provide increased capacity to one of the substrate reservoirs; and
an instrument interface module having a plurality of first connectors for connecting to one or more of the plurality of instrument connectors, and a plurality of second connectors for providing a connection between the instrument connectors and the substrate interface module when the substrate interface module is removably attached to the instrument interface module. - View Dependent Claims (33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51)
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52. A microfluidic device arranged on a sample substrate, the device comprising:
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a plurality of substrate reservoirs disposed on the substrate;
a plurality of microchannels disposed on the substrate, wherein the plurality of microchannels connects the plurality of substrate reservoirs, and wherein two or more of the microchannels are substantially parallel in a detection region on the substrate; and
a non-linear arrangement of a plurality of sampling capillary connection regions disposed on the substrate for interfacing with one or more sampling capillaries, wherein the sampling capillary connection regions are connected to the plurality of microchannels. - View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
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64. A microfluidic device arranged on a sample substrate, the device comprising:
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a plurality of substrate reservoirs disposed on the substrate;
a plurality of microchannels disposed on the substrate, wherein the plurality of microchannels connects the plurality of substrate reservoirs; and
two linear arrangements of two or more sampling capillary connection regions disposed on the substrate for interfacing with one or more sampling capillaries, the sampling capillary connection regions being connected to the plurality of microchannels, wherein for each linear arrangement, the sampling capillary connection regions are space approximately n*2.25 mm apart, where n is an integer having a value of from 1 to 24, inclusive. - View Dependent Claims (65)
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66. A method of simultaneously analyzing a plurality of samples in a plurality of microchannels on a microfluidic device, wherein the plurality of microchannels are substantially parallel along a first direction within a detection region on the microfluidic device, the method comprising the steps of:
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simultaneously exciting the samples in at least two of the microchannels in the detection region by focussing an excitation beam having two or more excitation wavelengths onto a first plane defined by the plurality of microchannels in the detection region such that the focussed excitation beam is elongated, having a major axis substantially perpendicular to the first direction, wherein the excitation beam impinges upon the detection region at a non-normal angle of incidence relative to the first plane, and wherein the excited samples emit radiation; and
simultaneously detecting the radiation emitted by the two or more excited samples using two or more detectors, wherein each of the detectors detects radiation having a specific polarization.
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68. A microfluidic device comprising:
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a fluid reservoir for holding a conducting fluid;
a capillary for supplying the fluid to the reservoir;
a voltage source having a first terminal and a second terminal;
a first electrode connected to the first terminal, wherein the first electrode is positioned at a first location in the reservoir; and
a second electrode connected to the second terminal, wherein the second electrode is positioned at a second location in the reservoir;
wherein when the level of the fluid within the reservoir is at least at the first location, an electric current is present between the first and second terminals, and wherein when the fluid level is below the first location such that there is no contact between the fluid and the first electrode, no electric current between the first and second terminals is present. - View Dependent Claims (69)
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70. A microfluidic device comprising:
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a first fluid reservoir for holding a conducting fluid;
a second fluid reservoir for holding the conducting fluid, wherein the first fluid reservoir is in fluid communication with the second fluid reservoir;
a capillary for supplying the fluid to the first reservoir;
a voltage source having a first terminal and a second terminal;
a first electrode connected to the first terminal, wherein the first electrode is positioned in the first reservoir; and
a second electrode connected to the second terminal, wherein the second electrode is positioned in the second reservoir;
wherein when the level of the fluid within one of the first and second reservoirs is at least at a first level, an electric current is present between the first and second terminals, and wherein when the fluid level is below the first level such that there is no contact between the fluid and one of the first and second electrodes, no electric current between the first and second terminals is present. - View Dependent Claims (71)
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72. An analytical system comprising:
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an analysis chip having a plurality of microchannels disposed thereon, wherein at least two of the plurality of microchannels are located in a detection region;
an optical illumination and detection subsystem including;
an illumination source for illuminating the at least two microchannels in the detection region with an excitation beam at a non-normal angle of incidence, said excitation beam having at least two excitation wavelengths, wherein the excitation beam simultaneously excites samples in the at least two microchannels in the detection region; and
at least two detectors, wherein each detector detects a specific range of wavelengths;
an instrument array including a plurality of interface components for providing control of analyses performed on the chip;
ana modular interface structure, including at least one module, for holding the chip and for interfacing the chip with the instrument array, wherein the at least one module is configured to interface with at least one of the interface components.
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73. An illumination and detection system for use in illuminating a plurality of samples in a plurality of microchannels located in a detection region on a microfluidic device, and for detecting radiation emitted from the detection region, wherein the microchannels are substantially parallel along a first direction within the detection region, the system comprising:
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an illumination source for providing an excitation beam, wherein the illumination source is configured so that excitation beam impinges at a non-normal angle of incidence onto a first plane defined by the plurality of microchannels in the detection region, wherein on the first plane the excitation beam is elongated, having a major axis substantially perpendicular to the first direction, and wherein the excitation beam simultaneously excites the samples in at least two of the microchannels so as to cause the excited samples to emit radiation;
one or more detectors, wherein each detector detects a specific range of radiation wavelengths; and
detection optics for directing radiation from the samples toward the one or more detectors such that the wavelengths of the emitted radiation within each specific radiation wavelength range are directed toward the corresponding detector.
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74. An illumination and detection system for use in illuminating a plurality of samples in a plurality of microchannels located in a detection region on a microfluidic device, and for detecting radiation emitted from the detection region, wherein the microchannels are substantially parallel along a first direction within the detection region, the system comprising:
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an illumination source for providing an excitation beam having two or more excitation wavelengths;
focussing optics for focussing the excitation beam onto a first plane defined by the plurality of microchannels in the detection region such that the focussed excitation beam is elongated, having a major axis substantially perpendicular to the first direction, wherein the excitation beam impinges upon the detection region at a non-normal angle of incidence relative to the first plane, and wherein the excitation beam simultaneously excites the samples in at least two of the microchannels so as to cause the excited samples to emit radiation;
two or more detectors, wherein each detector detects a specific range of radiation wavelengths and a specific polarization; and
detection optics for directing radiation from the samples toward the detectors such that the emitted radiation having both the specific polarization and wavelengths within the specific radiation wavelength range are directed toward the corresponding detector. - View Dependent Claims (75)
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Specification