Ultra high throughput microfluidic analytical systems and methods

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.

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.    
     
     
         2 . The system of  claim 1 , wherein the illumination source includes: 
 two or more laser sources, wherein each laser source emits a radiation beam having one of the excitation wavelengths; and    illumination optics for combining each of the radiation beams into the excitation beam.    
     
     
         3 . The system of  claim 1 , wherein the excitation beam is polarized in a direction parallel to the major axis.  
     
     
         4 . The system of  claim 1 , wherein the illumination source includes: 
 a first laser that emits a radiation beam having a first primary wavelength;    a second laser that emits a radiation beam having a second primary wavelength;    a third laser that emits a radiation beam having a third primary wavelength; and    wherein the illumination optics includes optical elements for combining the first, second and third radiation beams so as to form the excitation beam.    
     
     
         5 . The system of  claim 4 , wherein the illumination source further includes a fourth laser that emits a radiation beam having a fourth primary wavelength, and wherein the optical elements combine the fourth radiation beam into the excitation beam.  
     
     
         6 . The system of  claim 4 , wherein the optical elements include: 
 a first beamsplitter element for combining the radiation beam of the first laser with the radiation beam of the second laser so as to form a first combined radiation beam;    a second beamsplitter element for combining the first combined radiation beam with the radiation beam of the third laser so as to form the excitation beam.    
     
     
         7 . The system of  claim 4 , wherein the first, second and third primary wavelengths are different, and wherein each of the first, second and third primary wavelengths are one of approximately 633 nm, approximately 457 nm, approximately 532 nm, and approximately 355 nm.  
     
     
         8 . The system of  claim 1 , wherein the detection optics includes: 
 one or more beamsplitter elements, wherein each beamsplitter element is associated with one of the detectors, and wherein each beamsplitter element directs radiation having the specific range of wavelengths associated with one of the detectors toward that detector; and    a focusing element that focuses and directs the emitted radiation from the excited samples to the beamsplitter elements.    
     
     
         9 . The system of  claim 8 , wherein the focusing element is positioned between the detection region and the beamsplitter elements, and wherein the beamsplitter elements are linearly positioned relative to the focussing element and the detection region so as to form a linear arrangement.  
     
     
         10 . The system of  claim 8 , wherein the focusing element and the beamsplitter elements are positioned such that the linear arrangement is normal to the first plane.  
     
     
         11 . The system of  claim 1 , wherein each of the detectors includes a CCD array.  
     
     
         12 . The system of  claim 1 , wherein each of the detectors provides an output signal proportional to the radiation received from the detection region within its specific range of wavelengths, and wherein the system further includes a processor coupled to each of the detectors for analyzing the output signals of the detectors.  
     
     
         13 . The system of  claim 1 , wherein the microfluidic device includes at least two intersecting microchannels.  
     
     
         14 . The system of  claim 1 , wherein each of the plurality of microchannels has at least one cross-sectional dimension between about 0.1 and about 500 micrometers.  
     
     
         15 . The system of  claim 1 , wherein the detection optics includes: 
 one or more beamsplitter elements, wherein each beamsplitter element is associated with one of the detectors, and wherein each beamsplitter element directs radiation having a specific polarization toward the associated detector; and    a focusing element that focuses and directs the emitted radiation from the excited samples to the beamsplitter elements.    
     
     
         16 . An analytical system comprising: 
 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; an    a 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.    
     
     
         17 . 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, 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.    
     
     
         18 . 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 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.    
     
     
         19 . The system of  claim 18 , wherein each specific polarization is one of a linear polarization and a circular polarization.