Optical system and method for inspecting flourescently labeled biological specimens

Abstract

A system for imaging a fluorescently labeled sample is presented, The system comprises a capsule, which is a closable structure made of a material isolating the inside of the capsule from its surrounding environment, and which has a support stage for receiving the sample and carrying it thereinside during the imaging; and an optical device at least partly accommodated inside the capsule and operable to illuminate the sample with incident radiation to excite a fluorescent response of the sample, detect the fluorescent response, and generate data indicative thereof.

1 . A system for imaging a fluorescently labeled sample, the system comprising a capsule which is a closable structure made of a material isolating the inside of the capsule from its surrounding environment, and which has a support stage for receiving the sample and carrying it thereinside during the imaging; and a sensor arrangement accommodated inside the capsule and operable to detect for sensing one or more predetermined environmental condition inside the capsule, and comprises inlet and outlet means for adjusting said at least one environmental condition inside the capsule.  
   
   
       2 . The system according to  claim 1 , wherein the light environment inside the capsule during the imaging is sensed and maintained to be about 0.001 lux.  
   
   
       3 . The system according to  claim 1 , wherein said sensor arrangement comprises at least one temperature sensor.  
   
   
       4 . The system according to  claim 3 , wherein said sensor arrangement comprises at least one of the following: a light intensity sensor, an electromagnetic radiation sensor, a gas sensor, and a humidity sensor.  
   
   
       5 . The system according to  claim 4 , wherein said gas sensor is capable of detecting the content of oxygen in the vicinity of the sensor.  
   
   
       6 . The system according to  claim 1 , wherein said optical device comprises a light source system, an image formation system, and light directing/collecting optics having an objective lens arrangement and defining illumination and detection channels of light propagation.  
   
   
       7 . The system according to  claim 6 , wherein the light source system has a plurality of light sources, each operable to generate the incident radiation including a spectrum exciting a fluorescent response of the sample.  
   
   
       8 . The system according to  claim 6 , wherein said light directing/collecting optics comprises a filter arrangement.  
   
   
       9 . The system according to  claim 8 , wherein said filter arrangement comprises a spectral filter assembly accommodated in the optical path of light returned from the illuminated sample to select from the returned light the fluorescent response and direct it to the detection channel to propagate towards the image formation system.  
   
   
       10 . The system according to  claim 9 , wherein said filter arrangement comprises a spectral filter assembly in the optical path of the incident radiation generated by the light source system to select the desired exciting light and allow its incidence onto the sample.  
   
   
       11 . The system according to  claim 6 , wherein said light directing/collecting optics comprises a beam shaping assembly accommodated in the optical path of the incident radiation generated by the light source system.  
   
   
       12 . The system according to  claim 6 , wherein the image formation system comprises a detector arrangement.  
   
   
       13 . The system according to  claim 12 , wherein the detector arrangement comprises a single detector.  
   
   
       14 . The system according to  claim 13 , wherein said single detector is a CCD camera or a CMOS camera.  
   
   
       15 . The system according to  claim 14 , wherein said single detector is a cooled system.  
   
   
       16 . The system according to  claim 12 , wherein said detector arrangement has at least two different detectors.  
   
   
       17 . A system for imaging a fluorescently labeled sample, the system comprising: 
 a capsule, which is a closable structure made of a material isolating the inside of the capsule from surrounding environment, the capsule comprising a support stage for receiving the sample and carrying it thereinside during the imaging process in a manner enabling displacement of the sample with respect to an inspection plane, and having inlet and output channels operable to affect environment conditions inside the capsule;    an optical device at least partly accommodated inside the capsule and operable to illuminate the sample with incident exciting radiation to excite a fluorescent response of the sample, detect the fluorescent response, and generate data indicative thereof;    a sensor arrangement accommodated inside the capsule and operable to detect at least two of the following environment conditions inside the capsule: temperature, light intensity, electromagnetic radiation intensity, content of at least one gas in the capsule, and humidity; and to generate data indicative thereof; and    a control unit connectable to the capsule and response to said data indicative of the detected fluorescent response to output an image of the illuminated region of the sample, responsive to said data indicative of the at least one environment condition to operate the inlet and output channels of the capsule so as to provide a desired environment condition inside the capsule.