Detection of cancer using cellular autofluorescence

Abstract

Apparatus and methods especially useful for detection of cancer using cellular, Tryptophan-associated autofluorescence are described. The apparatus includes a light source to produce a beam of light transmitted to a tissue via a two-way fiber optic bundle which, in one embodiment, is passed through a conventional endoscope. The light beam excites the tissue, resulting in an emission of primarily cellular autofluorescence at a wavelength of about 330 nm. Light from the tissue is directed back through the fiber optic bundle and passes through a photodetector. The photodetector produces a signal, representative of the intensity of the Tryptophan-associated autofluorescence.

1 . A method for detection of cancerous cells, said method comprising the step of measuring an intensity of Tryptophan-associated autofluorescence emitted from a tissue sample.  
     
     
         2 . A method in accordance with  claim 1  wherein measuring an intensity of Tryptophan-associated autofluorescence emitted from the tissue sample comprises the step of measuring an intensity of autofluorescence emitted at a wavelength of about 300-400 nm.  
     
     
         3 . A method in accordance with  claim 1  wherein measuring an intensity of Tryptophan-associated autofluorescence emitted from the tissue sample comprises the step of measuring an intensity of autofluorescence emitted at a wavelength of about 320-340 nm.  
     
     
         4 . A method in accordance with  claim 1  wherein measuring an intensity of Tryptophan-associated autofluorescence emitted from the tissue sample comprises the step of measuring an intensity of autofluorescence emitted at a wavelength of about 330 nm.  
     
     
         5 . A method in accordance with  claim 1 , said method further comprising the step of exposing the tissue sample to a beam of light.  
     
     
         6 . A method in accordance with  claim 5  wherein said step of exposing the tissue sample to a beam of light comprises the step of exposing the tissue sample to a beam of light having a wavelength in a range of about 200 nm to about 400 nm.  
     
     
         7 . A method in accordance with  claim 5  wherein said step of exposing the tissue sample to a beam of light comprises the step of exposing the tissue sample to a beam of light having a wavelength in a range of about 270 nm to about 310 nm.  
     
     
         8 . A method in accordance with  claim 5  wherein said step of exposing the tissue sample to a beam of light comprises the step of exposing the tissue sample to a beam of light having a wavelength of about 290 nm.  
     
     
         9 . A method in accordance with  claim 5  wherein said step of exposing the tissue sample to a beam of light comprises the step of exposing the tissue sample to a beam of pulsed light having a wavelength equal to a whole multiple of a wavelength in the range about 200 nm to about 400 nm.  
     
     
         10 . A method in accordance with  claim 5  wherein exposing the tissue sample to a beam of ultraviolet light comprises the step of delivering the beam of light to the tissue sample using a two-way fiber optic bundle.  
     
     
         11 . A method in accordance with  claim 10  wherein delivering the beam of light to the tissue sample using a two-way fiber optic bundle comprises the step of passing the two-way fiber optic bundle through a biopsy channel of an endoscope.  
     
     
         12 . A method in accordance with  claim 1  wherein measuring the intensity of Tryptophan-associated autofluorescence comprises the step of visually representing the Tryptophan-associated autofluorescence using a charge-coupled device.  
     
     
         13 . A method in accordance with  claim 1  further comprising the step of applying a contrast agent to the tissue sample.  
     
     
         14 . A method in accordance with  claim 13  wherein applying a contrast agent to the tissue sample comprises the step of applying a contrast agent comprising an exogenous fluorescent chemical.  
     
     
         15 . A method in accordance with  claim 13  wherein applying a contrast agent to the tissue sample comprises the step of applying methylene blue to the tissue sample.  
     
     
         16 . A method comprising the steps of: 
 exposing a first tissue to a beam of ultraviolet light;    measuring an intensity of Tryptophan-associated autofluorescence emitted in the first tissue;    exposing a second tissue whose condition is known to a beam of ultraviolet light;    measuring an intensity of Tryptophan-associated autofluorescence emitted in the second tissue; and    comparing the intensity measurements of the first tissue sample to the intensity measurements for the second tissue sample whose condition is known to determine the degree of cancer in the first tissue.    
     
     
         17 . A method in accordance with  claim 16  wherein comparing the intensity measurements of the first tissue with the intensity measurements of the second tissue further comprises the step of comparing the intensity measurements at an emission wavelength of about 300-400 nm.  
     
     
         18 . A method in accordance with  claim 16  wherein comparing the intensity measurements of the first tissue with the intensity measurements of the second tissue further comprises the step of comparing the intensity measurements at an emission wavelength of about 320-340 nm.  
     
     
         19 . A method in accordance with  claim 16  wherein comparing the intensity measurements of the first tissue with the intensity measurements of the second tissue further comprises the step of comparing the intensity measurements at an emission wavelength of about 330 nm.  
     
     
         20 . A method in accordance with  claim 16  wherein said steps of exposing a first tissue to a beam of ultraviolet light and exposing a second tissue whose condition is known to a beam of ultraviolet light comprise exposing the first tissue and the second tissue to ultraviolet light having a wavelength in a range of about 200 nm to about 400 nm.  
     
     
         21 . A method in accordance with  claim 16  wherein said steps of exposing a first tissue to a beam of ultraviolet light and exposing a second tissue whose condition is known to a beam of ultraviolet light comprise exposing the first tissue and the second tissue to ultraviolet light having a wavelength in a range of about 270 nm to about 310 nm.  
     
     
         22 . A method in accordance with  claim 16  wherein said steps of exposing a first tissue to a beam of ultraviolet light and exposing a second tissue whose condition is known to a beam of ultraviolet light comprise the steps of exposing the first tissue and the second tissue to ultraviolet light having a wavelength of about 290 nm.  
     
     
         23 . A method in accordance with  claim 16  further comprising the step of producing a signal representative of the difference between the intensity measurements of the first tissue and the intensity measurements of the second tissue.  
     
     
         24 . A method in accordance with  claim 16  further comprising the step of obtaining a cytological sample representative of normal tissue.  
     
     
         25 . A method in accordance with  claim 24  further comprising the step of using the cytological sample as the first tissue.  
     
     
         26 . A method in accordance with  claim 24  further comprising the step of using the cytological sample as the second tissue whose condition is known.