Method and apparatus for examining tissue for predefined target cells, particularly cancerous cells, and a probe useful in such method and apparatus

Abstract

A method, apparatus and probe for examining tissue for the presence of target cells, particularly cancerous cells, by subjecting the tissue to be examined to a contrast agent containing small particles of a physical element conjugated with a biological carrier selectively bindable to the target cells. Energy pulses are applied to the examined tissue. The changes in impedance and/or optical characteristics of the examined tissue produced by the applied energy pulses are detected and utilized for determining the presence of the target cells in the examined tissue. In a described preferred embodiment, the applied energy pulses include laser pulses, and the physical element conjugated with a biological carrier is a light-sensitive semiconductor having an impedance which substantially decreases in the presence of light. The same probe used for detecting the targeted cells may also be used for destroying the cells so targeted.

1 . Apparatus for examining a tissue region for the presence of predefined target cells therein, comprising
 a voltage pulse source;   an optical pulse source;   a probe having an operative end for applying optical pulses and voltage pulses from said sources to the examined tissue region, and for detecting the reflections of said voltage pulses;   and a data processor system including an electrical measuring sub-system coupled to said probe for detecting the reflections of said voltage pulses, said reflections indicative of changes in electrical properties of said examined tissue region produced by at least one of said optical and voltage pulses, and for determining therefrom the extent of the presence of said target cells in the examined tissue region; the voltage pulses and optical pulses being applied concurrently.   
   
   
       2 . The apparatus according to  claim 1 , wherein said probe is also operative for detecting optical reflections of said optical pulses; and wherein said data processor system also includes an optical analyzer sub-system coupled to said probe for detecting the reflections of said optical pulses. 
   
   
       3 . The apparatus according to  claim 1 , wherein said probe includes a pair of spaced conductors at said operative end for applying said voltage pulses to said examined tissue, and an optical fiber centrally of said conductors for applying said optical pulses to said examined tissue. 
   
   
       4 . The apparatus according to  claim 3 , wherein said pair of spaced conductors are coaxial conductors, and said optical fiber is a core extending centrally of said coaxial conductors. 
   
   
       5 . The apparatus according to  claim 4 , wherein one of said coaxial conductors is an inner conductor in the form of a metal layer over said optical fiber, and the other of said coaxial conductors is an outer conductor enclosing said inner conductor and separated therefrom by a dielectric material. 
   
   
       6 . The apparatus according to  claim 5 , wherein said outer conductor is in the form of a flexible metal braid, and the end thereof at the operative end of the probe includes a rigid cap to facilitate manipulating the probe. 
   
   
       7 . The apparatus according to  claim 3 , wherein the end of at least one conductor at said operative end of the probe extends slightly past the respective end of said optical fiber to define an open cavity at said operative end of the probe. 
   
   
       8 . The apparatus according to  claim 5 , wherein said optical fiber extends through an opening in said outer conductor for connection to said optical pulse source. 
   
   
       9 . The apparatus according to  claim 3 , wherein said pair of spaced conductors are capacitor plates, and said optical fiber is located between said capacitor plates at said operative end of the probe. 
   
   
       10 . The apparatus according to  claim 3 , wherein said pair of spaced conductors at the operative end of the probe are configured to clamp between them the tissue to be examined. 
   
   
       11 . The apparatus according to  claim 1 , wherein said optical pulse source includes a laser supplying laser pulses, and wherein said probe includes an optical fiber for conducting said laser pulses to the operative end of the probe for application to the examined tissue. 
   
   
       12 . The apparatus according to  claim 3 , wherein said optical fiber in the probe also receives optical reflections of said optical pulses; said probe thus being operative for detecting optical reflections of said optical pulses; and wherein said data processor system also includes an optical analyzer sub-system coupled to said probe for detecting the reflections of said optical pulses. 
   
   
       13 . The apparatus according to  claim 2 , wherein said optical analyzer sub-system includes spectrum analyzer means and a splitting box; wherein said splitting box includes a beam splitter for directing a first part of the optical pulses from said optical pulse source to said optical fiber in the probe, and a second part to said spectrum analyzer means; and wherein said beam splitter also directs to said spectrum analyzer means said optical reflections received from the examined tissue region. 
   
   
       14 . The apparatus according to  claim 13 , wherein said spectrum analyzer means includes two spectrometers; and wherein said splitting box includes a polarizer which polarizes into two forms said second part of the optical pulse source and the optical reflections from the examined tissue region, and directs each polarization form to one of the two spectrometers. 
   
   
       15 . The apparatus according to  claim 1 , wherein said optical pulse source includes a light chopper for supplying said optical pulses to the probe at a controlled repetition rate. 
   
   
       16 . The apparatus according to  claim 15 , further comprising an impedance measuring sub-system including a lock-in-amplifier which is controlled in synchronism with said light chopper to increase a signal-to-noise ratio output of the amplifier. 
   
   
       17 . The apparatus according to  claim 1 , wherein said data processor system includes an audio output device which is actuated according to the determination of said data processor system as to the extent cancerous cells are present in the examined tissue. 
   
   
       18 . The apparatus according to  claim 1 , wherein said probe is flexible so as to be capable of being introduced into a subject's body via a catheter. 
   
   
       19 . The apparatus according to  claim 1 , wherein said probe is incorporated inside a biopsy needle. 
   
   
       20 . The apparatus according to  claim 19 , wherein said biopsy needle has a side cavity, and said operative end of the probe is aligned with said side cavity. 
   
   
       21 . The apparatus according to  claim 19 , wherein said biopsy needle has a sharp front edge, and said operative end of the probe is aligned with said sharp front edge. 
   
   
       22 . The apparatus according to  claim 1 , wherein said optical pulse source is a laser source capable of applying laser pulses of a relatively low intensity for detecting the presence of target cells in the examined tissue, and thereafter laser pulses of a high intensity for destroying detected target cells. 
   
   
       23 . The apparatus according to  claim 22 , wherein said laser source is capable of applying femtosecond laser pulses of an intensity of 100 nj to 1 mj for destroying the detected target cells. 
   
   
       24 . The apparatus according to  claim 1 , wherein said probe further includes an array of optical sensors at a known location with respect to said operative end of the probe for sensing the location and orientation of said operative end of the probe. 
   
   
       25 . A probe for use in examining a tissue region for the presence of predefined target cells therein, comprising:
 an operative end having at least one pair of spaced conductors for applying voltage pulses to the examined tissue region, and that detects the reflections of said voltage pulses, and that applies optical pulses via an optical fiber to the examined tissue region; the voltage pulses and the optical pulses being applied concurrently.   
   
   
       26 . The probe according to  claim 25 , wherein said pair of spaced conductors are coaxial conductors, and said optical fiber is a core extending centrally of said coaxial conductors. 
   
   
       27 . The probe according to  claim 26 , wherein one of said coaxial conductors serving as an inner conductor is in the form of a metal layer over said optical fiber, and the other of said coaxial conductors serving as an outer conductor encloses said metal layer and is separated therefrom by a dielectric material. 
   
   
       28 . The probe according to  claim 27 , wherein said outer conductor is in the form of a flexible metal braid, and the end thereof at the operative end of the probe includes a rigid cap to facilitate manipulating the probe. 
   
   
       29 . The probe according to  claim 25 , wherein the end of at least one conductor at said operative end of the probe extends slightly past the respective end of said optical fiber to define an open cavity at said operative end of the probe. 
   
   
       30 . The probe according to  claim 26 , wherein said optical fiber extends through an opening in outer one of said conductors for connection to an optical pulse source. 
   
   
       31 . The probe according to  claim 25 , wherein said pair of spaced conductors are capacitor plates, and said optical fiber is located between said capacitor plates at said operative end of the probe. 
   
   
       32 . The probe according to  claim 25 , wherein said pair of spaced conductors at the operative end of the probe are configured to clamp between them the tissue to be examined. 
   
   
       33 . The probe according to  claim 25 , wherein the end of said probe opposite to said operative end is manually graspable for manipulation with respect to the tissue to be examined. 
   
   
       34 . The probe according to  claim 25 , wherein said probe is flexible so as to be capable of being introduced into a subject's body via a catheter. 
   
   
       35 . The probe according to  claim 25 , wherein said probe is incorporated inside a biopsy needle. 
   
   
       36 . The probe according to  claim 35 , wherein said biopsy needle has a side cavity, and said operative end of the probe is aligned with said side cavity. 
   
   
       37 . The probe according to  claim 35 , wherein said biopsy needle has a sharp front edge, and said operative end of the probe is aligned with said sharp front edge. 
   
   
       38 . The probe according to  claim 25 , wherein said probe further includes an array of optical sensors at a known location with respect to said operative end of the probe for sensing the location and orientation of said operative end of the probe. 
   
   
       39 . Apparatus for examining a tissue region, comprising
 a voltage pulse source;   an optical pulse source;   a probe having an operative end for applying optical pulses and voltage pulses from said sources to the examined tissue region, and for detecting the reflections of said voltage pulses;   and a data processor system including an electrical measuring sub-system coupled to said probe for detecting the reflections of said voltage pulses, said reflections indicative of changes in electrical properties of said examined tissue region produced by at least one of said optical and voltage pulses, the voltage pulses and optical pulses being applied concurrently.