Systems and methods for measurement optimization

Abstract

The invention relates to methods and systems for detecting and or analyzing an agent in a sample with a chip having optical components incorporated therein.

1 . A chip for use in detecting an agent, the chip comprising: 
 a microfluidic channel incorporated into the chip, the microfluidic channel adapted to deliver a fluid that may contain an agent to a detection zone that lies at least partially in the channel;    an illuminator incorporated into the chip, the illuminator positioned to direct an excitation signal to the detection zone; and    a concave reflector incorporated into the chip and having a focal point substantially at the detection zone, the concave reflector positioned to receive an emission signal from the agent, when present in the detection zone, and to reflect the emission signal to a detector.    
     
     
         2 . The chip of  claim 1 , wherein the concave reflector is incorporated into the chip in a fixed relationship with respect to the channel.  
     
     
         3 . The chip of  claim 2 , further comprising: 
 a solid medium that provides a pathway from the microfluidic channel to the concave reflector along which the emission signal can travel without substantial refraction.    
     
     
         4 . The chip of  claim 3 , wherein the solid medium extends from a wall of the channel to the concave reflector.  
     
     
         5 . The chip of  claim 3 , further comprising: 
 a cover slip adapted to mate with the chip to enclose the channel, the concave reflector being incorporated into the cover slip.    
     
     
         6 . The chip of  claim 5 , wherein the cover slip and the solid medium each have a substantially similar refractive index.  
     
     
         7 . The chip of  claim 5 , wherein the solid medium provides a pathway from the microfluidic channel to the illuminator along which the excitation signal can travel without substantial refraction.  
     
     
         8 . The chip of  claim 1 , wherein the illuminator and the concave reflector are on opposed sides of the channel.  
     
     
         9 . The chip of  claim 8 , wherein the illuminator is a refractive illuminator having a focal point substantially located at the focal point of the concave reflector.  
     
     
         10 . The chip of  claim 8 , wherein the illuminator is a reflective illuminator having a focal point substantially located at the focal point of the concave reflector.  
     
     
         11 . The chip of  claim 8 , wherein the concave reflector includes an aperture positioned to allow the excitation signal to pass therethrough to prevent the excitation signal from being reflected toward the detector.  
     
     
         12 . The chip of  claim 8 , wherein the concave reflector is constructed and arranged to reflect at least a portion of the excitation signal.  
     
     
         13 . The chip of  claim 12 , further comprising: 
 a wavelength specific filter positioned to receive the emission signal and the excitation signal from the concave reflector, the wavelength specific filter adapted to direct at least a portion of the emission signal to the detector and to prevent the excitation signal from reaching the detector.    
     
     
         14 . The chip of  claim 12 , further comprising: 
 a second reflector constructed and arranged to receive and reflect the emission signal to the detector while allowing the excitation signal to pass thereby.    
     
     
         15 . The chip of  claim 1 , wherein the illuminator includes a refractive illuminator having a focal point substantially located at the focal point of the concave reflector and further wherein the illuminator and the concave reflector are positioned on a common side of the channel.  
     
     
         16 . The chip of  claim 15 , wherein the illuminator and the concave reflector are constructed and arranged such that overlap of the excitation signal and the emission signal is minimized.  
     
     
         17 . The chip of  claim 16  wherein the concave reflector includes a central aperture and further wherein the refractive illuminator is positioned at the central aperture.  
     
     
         18 . The chip of  claim 17 , further comprising: 
 a second reflector constructed and arranged to reflect the excitation signal back through the aperture and toward the refractive illuminator.    
     
     
         19 . The chip of  claim 18 , wherein the second reflector is substantially located at the focal point of the concave reflector.  
     
     
         20 . The chip of  claim 17 , further comprising: 
 a second reflector constructed and arranged to reflect the excitation signal across the emission signal at a position outside of the chip.    
     
     
         21 . The chip of  claim 1 , wherein the concave reflector has a collection half angle greater than 49 degrees within water in a rectangular channel.  
     
     
         22 . The chip of  claim 1 , wherein the concave reflector has a collection half angle greater than 78 degrees within water in a rectangular channel.  
     
     
         23 . The chip of  claim 1 , wherein the concave reflector has a collection half angle of 90 degrees within water in a rectangular channel.  
     
     
         24 . The chip of  claim 1 , wherein the reflector has a collector numerical aperture of 1.0 or greater.  
     
     
         25 . The chip of  claim 1 , wherein the reflector has a collector numerical aperture of 1.3 or greater.  
     
     
         26 . The chip of  claim 1 , wherein the reflector is a parabolic reflector.  
     
     
         27 . The chip of  claim 1 , wherein the illuminator includes a waveguide incorporated into the chip.  
     
     
         28 . The chip of  claim 27 , wherein the waveguide is constructed and arranged to illuminate the microfluidic channel with an evanescent excitation signal.  
     
     
         29 . The chip of  claim 1 , comprising a plurality of pairs of concave reflectors and illuminators, each pair associated with a corresponding detection zone.  
     
     
         30 . The chip of  claim 29 , wherein the chip comprises more than 50 pairs of concave reflectors and illuminators.  
     
     
         31 . The chip of  claim 29 , wherein the plurality of pairs of concave reflectors and illuminators are arranged in serial along a common channel.  
     
     
         32 . The chip of  claim 29 , wherein the chip comprises a plurality of channels, wherein the plurality of pairs of concave reflectors and illuminators are arranged about the plurality of channels.  
     
     
         33 . The chip of  claim 1 , wherein the detection zone is circular in shape.  
     
     
         34 . The chip of  claim 33 , wherein the detection zone has a diameter of about 1.7 microns.  
     
     
         35 . The chip of  claim 33 , wherein the illuminator has an illuminator numerical aperture between 0.18 and 0.20.  
     
     
         36 . The chip of  claim 1 , wherein the detection zone is elliptical in shape.  
     
     
         37 . The chip of  claim 1 , wherein the elliptical detection zone has a minor diameter of about 1.7 microns.  
     
     
         38 . The chip of  claim 1 , wherein the detection zone extends beyond the channel.  
     
     
         39 . The chip of  claim 1 , wherein the agent comprises a plurality of agents.  
     
     
         40 . The chip of  claim 1 , wherein the agent is a polymer.  
     
     
         41 . The chip of  claim 40 , wherein the polymer is a nucleic acid optionally selected from the group consisting of DNA or RNA.  
     
     
         42 . The chip of  claim 40 , wherein the polymer is a peptide or a polypeptide.  
     
     
         43 . The chip of  claim 1 , wherein the agent is a cell.  
     
     
         44 . The chip of  claim 1 , wherein the agent is a pathogen.  
     
     
         45 . The chip of  claim 1 , further comprising: 
 a registration feature for aligning the reflector relative to the detection zone.    
     
     
         46 .- 51 . (canceled)