Systems and methods for assessing biological samples

Abstract

An instrument for biological analysis includes a base, an excitation source, an optical sensor, an excitation optical system, and an emission optical system. The base is configured to receive a sample holder comprising a plurality of biological samples. The optical sensor is configured to receive emissions from the biological samples in response to the excitation source. The instrument may additionally include a sensor lens enclosed by a lens case and a focusing mechanism including a gear that engages the lens case, the focusing mechanism being accessible outside the enclosure for adjusting a focus. The may instrument further include a sensor aperture dispose along an emission optical path and a blocking structure disposed to cooperate with the sensor aperture such that none of the reflected radiation from an illuminated surface near the sample holder is received by the optical sensor that does not also reflect off another surface of the instrument.

1 . An instrument for biological analysis, comprising:
 an excitation source;   an optical sensor configured to receive emissions from a biological samples in response to the excitation source;   an excitation optical system disposed along an excitation optical path;   an emission optical system disposed along an emission optical path;   an imaging unit comprising:
 a cavity comprising a first surface, an opposing second surface, and a threaded housing; 
 a sensor lens; and 
 a focusing mechanism comprising a focusing gear configured to engage the threaded housing so as to move the sensor lens along an optical axis thereof; 
 wherein the first surface comprises a surface of the sensor lens; 
 wherein the second surface comprises an optical sensor circuit board; and 
 wherein the sensor lens is adjustable by indirect engagement via the focusing gear. 
   
     
     
         2 . An instrument for biological analysis, comprising:
 an excitation source;   an optical sensor configured to receive emissions from the biological samples in response to the excitation source;   an excitation optical system disposed along an excitation optical path;   an emission optical system disposed along an emission optical path;   a sensor lens configured to direct emissions from at least some of the biological sample onto the optical sensor;   an illuminated surface disposed along the excitation optical path, the illuminated surface configured to produce reflected radiation comprising radiation from the excitation source that is reflected by the illuminated surface;   a radiation shield, comprising:
 a sensor aperture dispose along the emission optical path; and 
 a blocking structure configured to cooperate with the sensor aperture such that none of the reflected radiation is received by the optical sensor that does not also reflect off another surface of the instrument. 
   
     
     
         3 . An instrument for biological analysis, comprising:
 an excitation source;   an optical sensor configured to receive emissions from the biological samples in response to the excitation source;   an excitation optical system disposed along an excitation optical path;   an emission optical system disposed along an emission optical path;   an energy or power detection unit comprising:
 an energy or power sensor located outside the optical paths; and 
 a light pipe disposed adjacent the a a beamsplitter and configured to transport radiation from the beamsplitter to the power sensor. 
   
     
     
         4 - 6 . (canceled) 
     
     
         7 . An instrument according to  claim 1  further comprising a beamsplitter disposed along both the excitation optical path and along the emission optical path. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The instrument according to  claim 7 , further comprising:
 a base configured to receive a sample holder comprising a plurality of spatially separated reaction regions for processing one or more biological samples;   wherein the excitation source is configured to produce a first excitation beam characterized by a first wavelength and a second excitation beam characterized by a second wavelength that is different from the first wavelength.   
     
     
         11 - 16 . (canceled) 
     
     
         17 . The instrument according to  claim 1 , wherein at least some of the emissions comprise a fluorescent emission from at least some of the biological samples in response to at least one of the excitation beams. 
     
     
         18 - 21 . (canceled) 
     
     
         22 . The instrument according to  claim 7 , further comprising a mirror disposed along the excitation optical path between the base and the beamsplitter. 
     
     
         23 . The instrument according to  claim 10 , wherein the base comprises a sample block assembly configured to control the temperature of the sample holder or biological samples. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . The instrument according to  claim 10 , wherein the base comprises a thermal cycler configured to perform a PCR assay. 
     
     
         28 - 32 . (canceled) 
     
     
         33 . The instrument according to  claim 10 , wherein the sample holder comprises a microtiter plate and the reaction regions comprise at least 96 well, at least 384, or at least 1536 wells. 
     
     
         34 - 37 . (canceled) 
     
     
         38 . The instrument according to  claim 1 , wherein the excitation optical system comprises a sample lens configured to direct the excitation beams toward the base. 
     
     
         39 . The instrument according to  claim 38 , wherein the sample lens comprises a field lens configured to extend over the plurality of spatially separated regions. 
     
     
         40 - 43 . (canceled) 
     
     
         44 . The instrument according to  claim 38 , wherein the sample lens comprises a plurality of lenses corresponding to the plurality of reaction regions. 
     
     
         45 - 49 . (canceled) 
     
     
         50 . The instrument according to  claim 7 , wherein the beamsplitter comprises a 50/50 beamsplitter. 
     
     
         51 - 54 . (canceled) 
     
     
         55 . The instrument according to  claim 1 , wherein the excitation light source comprises a light emitting diode. 
     
     
         56 - 70 . (canceled) 
     
     
         71 . The instrument according to claim  68 , wherein the excitation filters comprise a plurality of filters together providing a plurality of band passes suitable for fluorescing one or more of a SYBR® dye or probe, a FAM™ dye or probe, a VIC® dye or probe, a ROX™ dye or probe, or a TAMRA™ dye or probe. 
     
     
         72 . The instrument according to claim  68 , wherein the excitation filters are mounted onto a rotatable filter wheel configure to move each of the filters into and out of the excitation beam path. 
     
     
         73 . The instrument according to  claim 1 , wherein the excitation source comprises a plurality of individual excitation sources. 
     
     
         74 - 81 . (canceled) 
     
     
         82 . The instrument according to  claim 10 , further comprising a heated cover disposed adjacent the base and including a plurality of apertures configured to correspond to the plurality of reaction regions. 
     
     
         83 . The instrument according to  claim 7 , further comprising a 50/50 beamsplitter, wherein the beamsplitter:
 passes the first excitation beam and the second excitation beam; and   passes the first emission beam and the second emission beam.