Abstract:
A sensor probe for in-situ measurement of pH in a human tissue (e.g., cardiovascular) environment comprises a hollow needle having a tip and a back end. The tip is insertable into the tissue. An optic cable comprises a light conduit surrounded by a cladding. A first end of the light conduit is inserted from the back end of the needle and extends to within a predetermined distance of the tip to define a cavity within the tip. A porous dye layer is contained within the cavity, wherein the dye layer has a response to excitation light delivered through the light conduit that varies according to the pH of the tissue environment. An overcoat layer is deposited on the dye layer, wherein the overcoat layer is ionically permeable and substantially opaque at a light wavelength corresponding to the variable response of the dye layer.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     Not Applicable. 
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
     Not Applicable. 
     BACKGROUND OF THE INVENTION 
     The present invention relates in general to monitoring pH levels in human tissue (such as ischemia in cardiac tissue), and, more specifically, to a microsensor needle adapted to in-situ pH measurement in human tissue. 
     It is known in the field of cardiac surgery that the pH of heart tissue can be indicative of conditions in which the tissue receives insufficient oxygen. If the heart does not have sufficient oxygen, ischemia can occur. Measurement of the pH can be performed using an optical sensor having a material which fluoresces in accordance with the pH of the environment into which the florescent material is immersed (e.g., blood or tissue). For example, U.S. Pat. No. 4,798,783 to Yafuso et al discloses a micro pH sensor providing a dye material at the end of an optical fiber. Excitation light is transmitted down the optical fiber to the dye material which is selected to either fluoresce or to specifically absorb the excitation light. The ionic content of the fluidic environment into which the dye material is immersed affects the florescent or absorbing properties of the material. Light from the dye material travels back up the optical fiber to a detector for characterizing the pH. Since the excitation properties of the material also depend upon the temperature, a thermistor or other temperature sensor is typically included in the sensor probe. The emitted/returned light and the temperature are utilized by conventional algorithms to determine a pH value. 
     Prior art micro-sensors have typically employed glass probes. Such probes are relatively expensive and, even though they are smaller than some other types of probes, are still sufficiently large to require the creation of a passage through heart tissue having a size that can cause cellular damage. Moreover, existing probe designs have been difficult to sterilize and have had a relatively short shelf life. There is a need in the art to provide a device and method for manufacturing the device which is capable of measuring pH of tissue during cardiovascular surgery or other interrogation of human tissue that is cost effective, has a relatively long shelf life, is easy to use and sterilize, and reduces damage to tissue. Moreover, there is a need to provide a microsensor that is easily placed in a wide variety of tissue types and locations. 
     SUMMARY OF THE INVENTION 
     The invention utilizes a needle to encase the end of a light conduit and to retain a dye layer and an overcoat layer in a manner that achieves low manufacturing cost while obtaining accurate pH measurements from a very small device which is easy to use and sterilize, easy to insert or attach to a patient, and which has a long shelf life. 
     In one aspect of the invention, a sensor probe for in-situ measurement of pH in a human tissue environment comprises a hollow needle having a tip and a back end. The tip is insertable through tissue into the human tissue environment. An optic cable comprises a light conduit surrounded by a cladding. A first end of the light conduit not covered by the cladding is inserted from the back end of the needle and extends to within a predetermined distance of the tip to define a cavity within the tip. A porous dye layer is contained within the cavity adjacent to the first end of the light conduit, wherein the dye layer has a response to excitation light delivered through the light conduit that varies according to the pH of the human tissue environment. An overcoat layer is deposited on the dye layer, wherein the overcoat layer is ionically permeable and substantially opaque at a light wavelength corresponding to the variable response of the dye layer. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a side view of a sensor probe and connector cables of the present invention. 
         FIG. 2  is a cross-sectional view of the sensor probe. 
         FIG. 3  is a perspective view of the probe tip. 
         FIG. 4  is a cross-sectional view of the probe tip in greater detail. 
         FIG. 5  is a top view showing a first embodiment of a stitch-on disk. 
         FIG. 6  is a top view showing a second embodiment of a stitch-on disk. 
         FIG. 7  is a flowchart showing a preferred manufacturing method for making the sensor probe of the present invention. 
         FIG. 8  illustrates the use of a spacing jig for receiving the needle tip. 
         FIG. 9  illustrates the insertion of an optic cable through the needle to the spacing jig for orienting the optic cable with respect to the needle. 
         FIG. 10  illustrates a preferred method for applying the dye layer and overcoat layer to the cavity in the needle tip. 
         FIG. 11  is a side view of a sensor probe in a straight configuration. 
         FIG. 12  is a side view of a sensor probe having a narrow housing adapted to be insertable into a body. 
         FIG. 13  is a top view showing a third embodiment of a stitch-on disk. 
     
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     Referring to  FIG. 1 , a sensor probe assembly  10  includes a needle section  11 , a housing section  12 , and a cable bundle section  13 . Needle section  11  includes a hollow, cylindrical needle  15  having a tip  16  and a backend  17  which is retained in housing section  12 . Needle  15  is preferably comprised of stainless steel. Needle tip  16  has a planar profile that is slanted at a predetermined angle with respect to a longitudinal axis of needle  15 . A first end of a light conduit  18  of an optic cable is contained within needle  15  and is spaced a predetermined distance from tip  16  in order to create a cavity for containing a porous dye layer  20  and an overcoat layer  21 . Housing section  12  includes a main body  23  and a stitch-on disk  24 . Main body  23  receives backend  17  of needle  15  and secures it therein. A thermistor  25  is attached to the backend  17  of needle  15  by a heat conductive adhesive  26 . A thermistor such as the A070M-SC30BF10A from Thermometrics, Inc., can be employed. A signal wire  27  connects thermistor  25  to an electrical connector  28  in wire bundle section  13 . Main body  23  has an integral support arm  30  for receiving optic cable  31  so that optic cable  31  can be kept out of the way during use. Optic cable  31  includes a cladding  32  which is removed at the first end where light conduit  18  is received by needle  15 . A plastic optic fiber such as the SH-2001-J fiber from Mitsubishi Rayon Company Ltd may be used. 
     Cable bundle section  13  includes an outer jacket  35  for retaining thermistor signal wire  27  together with the intermediate and second end portions of optical cable  31 . The second end of optic cable  31  includes an optical connector  36  for joining with a control module having a light emitter and a light detector for interfacing with optic cable  31  and having an electronic controller for receiving signals from the thermistor and for performing the known operations for calculating a pH value. 
     The sensor probe assembly  10  is shown in greater detail in cross-section in  FIG. 2 . A first end  40  of the light conduit or fiber is retained inside needle  15  where the cladding has been removed. The end of the cladding  32  abuts the back end  17  of needle  15 . A cylindrical ferrule  41  is placed over the joint between cladding  32  and needle end  17  and is attached by epoxy  42  for holding ferrule  41  in place. Ferrule  41  is preferably made of stainless steel. 
     Thermistor  25  thermally contacts needle  15  and is held in place by a thermally-conductive adhesive  26  (such as T7110 from Epoxy Technology, Inc.). In order to retain the needle and thermistor assembly in housing  23 , after the thermistor is attached to the needle then tip  16  of needle  15  is pushed through an aperture  43  in housing main body  23  and then the backend  17  of the needle together with the thermistor, its wiring, and the ferrule are fixed in place by injecting epoxy  44  to fill the remaining space in the interior of main body  23 . 
     Referring to  FIG. 3 , first end  40  of light conduit  18  is located with respect to tip  16  of needle  15  in order to create a cavity  45  as follows. Tip  16  is cut to have a planar profile that is slanted at a predetermined angle  46  with respect to a longitudinal axis  47  of the needle. Likewise, light conduit  40  has an end face that is slanted to be substantially parallel with the planar profile of tip  16 . Upon insertion of light conduit  18  through the backside of needle  17 , the insertion length and orientation are controlled in order to maintain a gap  48  between the end of light conduit  40  and tip  16 , thereby creating cavity  45  of a predetermined size. In a preferred embodiment, angle  46  is about 30°. The most preferred needle size is about 22 gauge and the stainless steel needle preferably has a length of about 10 mm. Preferably, the length of gap  48  is equal to about 0.2 mm resulting in a slanted cavity having a longitudinal thickness of 0.2 mm. In addition to facilitating entry of the needle into and through human tissue, the slanted tip allows for a greater contact surface area between the dye and overcoat layers and the cardiac environment, thereby providing an increased sensitivity of detection. 
       FIG. 4  shows needle tip  16  inserted into a cardiovascular environment  50 . When an acidic pH associated with ischemia is present, ions from cardiac environment  50  migrate through overcoat layer  21  into dye layer  20 . Incident excitation light  51  illuminates dye layer  20  via light conduit  18 . After the excitation light is turned off, a response in the form of emitted light from dye layer  20  returns up through light conduit  18  in the form of emitted light  52 . In a preferred embodiment, the intensity of emitted radiation  52 , along with the measured temperature are used to characterize pH in a known manner. Porous dye layer  20  can comprise any known material such as an ATPS-cellulose material. Overcoat layer  21  deposited on the dye layer is ionically permeable and is substantially opaque at light wavelengths corresponding to the excitation light and the emitted light of dye layer  20 . In one preferred embodiment, excitation light is provided by lasers at 410 nm and 470 nm and the emitted light is at a wavelength of 520 nm, and overcoat layer  21  is substantially opaque at all three frequencies so that ambient light does not interfere with the sensor. 
       FIG. 5  shows a top view of housing section  12  illustrating one embodiment for a stitch-on disk  24  to facilitate suturing of the sensor probe in place after inserting the needle tip into tissue of interest. In particular, narrow portions  55  are provided so that sutures can be looped around the narrow portions to securely retain the sensor probe in place. Likewise, in  FIG. 6  a plurality of star-shaped projections  56  perform the same function. 
     The right angle orientation for handling the optic cable and cable bundle shown in  FIGS. 1 and 2  is especially adapted for certain types of cardiovascular surgery. For other monitoring applications, a straight device as shown in  FIG. 11  is more desirable. The housing in  FIG. 11  retains a stitch-on disk but the support for the cable bundle is coaxial with the needle section. 
     For other tissue monitoring applications, it is desirable to provide a sensor probe that is insertable through the skin or other intervening tissue to reach the tissue of interest.  FIG. 12  shows another embodiment having a shortened needle section and a reduced-diameter housing section without a stitch-on disk, whereby the sensor probe is easily insertable into a body of a patient. 
       FIG. 13  shows yet another embodiment for providing a stitch-on support disk with indentations to be used for suturing. 
     Turning now to a preferred low cost manufacturing method for the sensor probe of the present invention in  FIG. 7 , a hollow, cylindrical, stainless steel needle is cut at its tip at an angle of 30° in step  60 . In step  61 , the first end of an optic cable is polished at an angle (e.g., in a polishing machine) to provide a 30° slant to the end of the optic cable. After polishing the end to the desired shape, cladding is stripped off the first end of the optic cable in step  62 . The stripped end of the optic cable may have a length of about 10 mm, for example. In order to obtain a desired gap and proper orientation of the light conduit inside the needle, a spacing jig  77  as shown in  FIG. 8  is employed. A receptacle  78  in spacing jig  77  is shaped as a cylindrical tunnel for receiving needle tip  16 . A finger  79  is adapted to be received within the interior of needle tip  16  and to extend a predetermined distance into the interior. Finger  79  has a slanted surface matching the slant of the end of the light conduit.  FIG. 9  shows needle tip  16  inserted all the way into spacing jig  77  and illustrates the insertion of light conduit  18 . Light conduit  18  advances through the needle until it abuts the slanted face of finger  79 . 
     Returning to  FIG. 7 , after the spacing jig is attached to the needle tip in step  63  and the light conduit is advanced through the needle until the first end abuts the finger and matches its orientation in step  64 , the optic cable and needle are fixed together in step  65 . In a preferred embodiment, a ferrule is slid over the needle and optic cable to bridge the back end of the needle and the cladding of the optical cable and then adhesive is applied around the ferrule. The spacing jig is removed in step  66  and then the thermistor is mounted to the backend of the needle using a heat conductive epoxy in step  67 . In step  68 , the signal wires of the thermistor are soldered to the thermistor and then the wires are bundled with the optic cable in step  69  by applying an outer cover over the bundle. 
     The needle assembly is mounted to the plastic housing in step  70 . In a preferred embodiment, a fixture is provided for holding the needle assembly in the proper position within the plastic housing while epoxy is injected into the interior of the plastic housing. A dye solution is prepared in step  71  and then daubed into the cavity inside the needle tip. The tip is then dipped into a regeneration bath and dried in step  72 . In step  73 , a carbon black solution is prepared and the tip with the dye layer already formed is dipped into the carbon black solution. After drying, the needle tip is dipped in a triacetin solution  74 . Final drying and cleaning are performed in step  75  and then the sensor probe may be packaged, stored, and distributed for use. 
       FIG. 10  shows the formation of the chemical layers in greater detail. As an initial step, the needle tip and optical fiber ends are washed with ethanol and well dried. An HTPS-cellulose solution of the type known in the art is prepared in a vessel  80 . For example, a dye-labeled cellulose solid may be obtained by 1) mixing acetoxypyrenetrisulfonic acid trichloride with acetone, a sodium carbonate buffer, and aminoethylcellulose powder, 2) adding to salt water and decomposing by heating, and 3) filtering out the resulting solids. The solid is then mixed with 4-methylmorpholine-N-oxide to provide an HTPS-cellulose solution. An applicator  81  such as a thin plastic rod is dipped into the cellulose solution and touched to the tip of the needle. The solution covers the end of the optical fiber and then the needle tip is immersed into a 5% glycerol solution for 2 minutes as shown at  82 . Thereafter, the resulting dye layer is dried at room temperature for five hours as shown at  83 . 
     In order to create the overcoat layer, a suspended-polymer carbon black solution is placed in a vessel  84 . The carbon black solution may be obtained by mixing into deionized water dextran (e.g., Sigma D5376) and carbon black (e.g., a blend of Marasperse CBOS-4 and Monarch-700). The resulting solution is insonified and then mixed with cross-link solution comprising 1,6-hexyldiamine and ethyleneglycol diglycidylether. The needle tip is dipped into the cross-linker solution for about 2 minutes and then dipped into a triacetin solution in a vessel  85  to provide a hygroscopic surface. The sensor is then dried at room temperature for at least 12 hours as shown at  86 . Thereafter, the sensor tip may be immersed in a phosphate buffer with a pH of about 7.0 for ten hours and then dried again.