Methods of monitoring effects of chemical agents on a sample

Abstract

The invention provides methods and systems for monitoring effects of chemical agents on optical signals produced by samples in response to the chemical agents. Preferred methods comprise application of multiple chemical agents that interact to alter an optical signal from the sample. Methods and systems of the invention also comprise monitoring an optical signal from an endogenous chromophore upon application of a chemical agent to a sample. Methods and systems of the invention also comprise the use of triggers, atomizers and image alignment to enhance the results of methods described herein.

1 - 32 . (canceled).  
     
     
         33  A method for observing effects of a chemical agent on a tissue sample, the method comprising the steps of: 
 dispensing a chemical agent on a tissue sample;    initiating a measurement period relative to the dispensing step;    compensating for motion of the sample during the measurement period; and    measuring at least one optical signal from the sample within the measurement period.    
     
     
         34  The method of  claim 33 , wherein the compensating step comprises capturing a plurality of sequential images of the tissue sample during the measurement period and aligning a subset of the plurality of images.  
     
     
         35  The method of  claim 33 , wherein the initiating step comprises providing an automated triggering signal.  
     
     
         36  The method of  claim 33 , wherein the at least one optical signal comprises at least one of fluorescent light and backscatter light.  
     
     
         37  The method of  claim 33 , wherein the at least one optical signal comprises both fluorescent light and backscatter light.  
     
     
         38  The method of  claim 33 , wherein the measuring step comprises determining at least one of a fluorescence spectrum and a reflectance spectrum.  
     
     
         39  The method of  claim 33 , wherein the chemical agent comprises acetic acid.  
     
     
         40  The method of  claim 33 , wherein the chemical agent comprises at least one member of the group consisting of acetic acid, formic acid, propionic acid, butyric acid, Lugol's iodine, Shiller's iodine, methylene blue, toluidine blue, osmotic agents, ionic agents, and indigo carmine.  
     
     
         41  The method of  claim 33 , wherein the tissue sample comprises cervical tissue.  
     
     
         42  The method of  claim 33 , wherein the tissue sample comprises at least one member selected from the group consisting of cervical tissue, colorectal tissue, skin, uterine tissue, and epithelial tissue.  
     
     
         43  The method of  claim 33 , wherein the tissue sample is in vivo.  
     
     
         44  The method of  claim 33 , further comprising the step of: 
 identifying a classification of the tissue based at least in part on the at least one optical signal.    
     
     
         45  The method of  claim 44 , wherein the classification comprises a member of the group consisting of Normal, CIN I, Normal/CIN I, CIN II, CIN m, and CIN II/III.  
     
     
         46  The method of  claim 44 , further comprising the step of: 
 representing the classification on a display.    
     
     
         47  The method of  claim 46 , wherein the representing step comprises superimposing a color on an image of the tissue sample.  
     
     
         48  The method of  claim 46 , further comprising the step of: 
 determining an area of the tissue sample for biopsy.    
     
     
         49  An apparatus for observing effects of a chemical agent on a tissue sample, the apparatus comprising: 
 a timer adapted to track a measurement period relative to a dispensing of a chemical agent on a tissue sample; and    a probe comprising probe optics adapted to illuminate the tissue sample and to collect light from the tissue sample within at least part of the measurement period.    
     
     
         50  The apparatus of  claim 49 , further comprising a camera adapted to obtain a plurality of images for compensating for motion of the tissue sample during the measurement period.  
     
     
         51  The apparatus of  claim 49 , wherein the probe optics comprise at least one light source.  
     
     
         52  The apparatus of  claim 51 , wherein the at least one light source comprises at least one of a UV light source and a white light source.  
     
     
         53  The apparatus of  claim 52 , wherein the at least one light source comprises a UV light source and a white light source.  
     
     
         54  The apparatus of  claim 51 , wherein the at least one light source comprises at least one member of the group consisting of a nitrogen laser, a frequency-tripled Nd:YAG laser, and a xenon flash lamp.  
     
     
         55  The apparatus of  claim 49 , further comprising a dispenser adapted to dispense the chemical agent on the tissue sample.  
     
     
         56  The apparatus of  claim 55 , wherein the dispenser comprises an atomizer.  
     
     
         57  The apparatus of  claim 49 , further comprising a disposable sheath configured to cover at least a portion of the probe.  
     
     
         58  The apparatus of  claim 49 , further comprising a detector from which a spectral result is obtained.  
     
     
         59  The apparatus of  claim 49 , wherein the probe optics are adapted to collect at least one of fluorescent light and backscatter light from the tissue sample.  
     
     
         60  The apparatus of  claim 49 , wherein the probe optics are adapted to collect fluorescent light and backscatter light from the tissue sample.  
     
     
         61  The apparatus of  claim 49 , further comprising a spectrometer adapted to obtain a spectral result from the collected light.  
     
     
         62  The apparatus of  claim 49 , further comprising a colposcope adapted to provide an image of the tissue sample.