Abstract:
A bio-probe having a base and a tip and also including a set of at least four conductors extending longitudinally along the bio-probe, the conductors being coated with dielectric material. Also, at least four of the conductors define a spot where the dielectric material has been removed, thereby defining an electrical contact site. In addition, the bio-probe is less than 2.5 mm thick in its greatest transverse dimension along a longitudinal portion extending from the tip to a point 6 cm proximal of the tip.

Description:
RELATED APPLICATION 
       [0001]    This application is a continuation-in-part of application Ser. No. 10/760,856, filed Jan. 20, 2004, which is a continuation in part of application Ser. No. 10/429,652 filed May 5, 2003, now U.S. Pat. No. 6,892,438, issued May 17, 2005, which is a divisional of Ser. No. 09/886,322, filed Jun. 21, 2001, now U.S. Pat. No. 6,560,472, issued May 6, 2003. 
     
    
     STATEMENT OF GOVERNMENTAL SUPPORT 
       [0002]    This invention was made with government support under grant No. 1R43MH59502-01 awarded by the Small Business Research Program of the Department of Health and Human Services of the Public Health Service. The government has certain rights in the invention. 
     
    
     BACKGROUND OF THE INVENTION 
       [0003]    The construction of a brain probe assembly to be employed in brain research is quite challenging from both a structural and an electrical standpoint. 
         [0004]    Structurally, probes must not fray or in any way come apart when pushed through the dura, a tough membrane covering the brain, and other brain tissue. Probes should have enough strength and rigidity to broach the dura without the need for assistance by, for example, a guide tube or an initial incision. 
         [0005]    Moreover, probes must not break, running the risk of leaving a fragment in the brain. Also, they must not cause undue damage to tissue at the sensing site. Inevitably, the tissue separating the sensing site from the brain exterior will suffer some damage as a probe is pushed to its destination. A small cross-section probe, however, may cause less damage as it is pushed to its destination. It is best to avoid having a sharp tip or any sharp edges, however, as this could cause blood vessels to be severed during the insertion process. 
         [0006]    Electrically, one should note that the electric field signals in the brain, which the probe is designed to detect, are typically of the order of 100 to 500 μvolts. The low amplitude of these signals makes it necessary to amplify them as physically close as possible to their source. In fact, the signals involved are so minute that variations in circuit geometry could well affect significantly the detection processing of the signals. It is also highly desirable to minimize cross-talk between any two signals. 
         [0007]    Additionally, it is generally advantageous for a brain probe to become flexible after being inserted so that the motion of the brain within the brain pan is not resisted by the probe. In the worst case this could cause tissue tearing. To insert a brain probe, however, it is better for the probe to be in a rigid state. Given the tight geometries allowable for brain probe design, these requirements are difficult to meet simultaneously. 
         [0008]    Further, a tube-like device known as a canula is generally used for inserting devices into the brain. Being able to fit through a canula, to a desired depth, is an important and desirable attribute of a brain probe. 
       SUMMARY OF THE INVENTION 
       [0009]    In a first, separate aspect, the present invention may take the form of a brain probe that includes a core having a distal end and a proximal end and a dielectric coating, over the core. In addition, a set of traces are located on the dielectric coating and a dielectric layer that is deposited over the traces defines an aperture for each trace, wherein the trace is exposed, thereby constituting an electrical contact point. Also, a set of insulated wires is each electrically connected to a trace and a conductive tube is affixed to the proximal end of the core, covering the wires. 
         [0010]    In a second separate aspect, the present invention is a bio-probe having a base and a tip and also including a set of at least four conductors extending longitudinally along the bio-probe, the conductors being coated with dielectric material. Also, at least four of the conductors define a spot where the dielectric material has been removed, thereby defining an electrical contact site. Also, the bio-probe is less than 2 mm thick in its greatest transverse dimension along a longitudinal portion extending from the tip to a point 6 cm proximal of the tip. 
         [0011]    In a third separate aspect, the present invention is a brain probe assembly for use accessing a target brain type to a target depth. The assembly includes a canula and a brain probe having a distal portion sized to fit through the canula and to extend into the target brain type to the target depth. Also, the brain probe includes 4 mutually electrically isolated electrical contact points. 
         [0012]    The foregoing and other objectives, features and advantages of the invention will be more readily understood upon consideration of the following detailed description of the preferred embodiment(s), taken in conjunction with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIG. 1  is an exploded perspective view of bio-probe assembly according to the present invention. 
           [0014]      FIG. 2  is a front view of the. circuit card assembly of the bio-probe assembly of claim  1 . 
           [0015]      FIG. 3  is an expanded perspective view of the tip of the bio-probe assembly of  FIG. 1 . 
           [0016]      FIG. 4  is a greatly expanded cross-sectional view of the tip of the bio-probe assembly of  FIG. 1 . 
           [0017]      FIG. 5  is a side view of an alternative embodiment of a bio-probe, according to the present invention. 
           [0018]      FIG. 6  is a cross-sectional view of the bio-probe of  FIG. 5 , taken along line  6 - 6  of  FIG. 5 . 
           [0019]      FIG. 7  is a side view of an alternative embodiment of a brain probe, according to the present invention. 
           [0020]      FIG. 8  is a side view of the brain probe of  FIG. 7 , inserted into a brain and intersecting a brain organ. 
           [0021]      FIG. 9  is a sectional view of the brain probe of  FIG. 7 , taken along view line  9 - 9 . 
           [0022]      FIG. 10  is a side view of a wire holding ring, an element of the brain probe of  FIG. 7 . 
           [0023]      FIG. 11  is an expanded side cut-away of a portion of the brain probe of  FIG. 7 . 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0024]    A preferred embodiment of a brain probe or bio-probe assembly  10 , according to the present invention is composed of a probe core  12  and a handle core  14 . The probe core  12  is made of tungsten, chosen for its material stiffness and tensile strength. Probe core  12  is preferably straight. To achieve this end, a straightening machine that pulls on core  12 , thereby creating tensile stress and annealing core  12  may be used. During further operations, a vacuum chuck may be used to hold core  12  in place. A tip or distal end  20  of probe core  12  has a diameter of 200 microns (8.0 mils) and a base or proximal end  24  of core  12  has a diameter of 600 microns (24 mils). In addition, core  12  is 89 mm (3.5″) long. The tip  20  is preferably formed by way of centerless grinding. Probe core  12  should be electro polished so that the deposition of materials onto it (see below) can be accomplished efficiently and so that the finished assembly  10  can pass through brain tissue as smoothly as possible. Alternatively, probe core  12  can be left in a comparatively rough state and coated with a coat of epoxy that is thick enough to minimize capacitance between core  12  and the traces  50  (discussed below). The comparatively rough state of the probe core actually helps to effect the binding of the epoxy to the probe core. One type of epoxy that can be used is the epoxy  377  discussed further below. 
         [0025]    For ease of assembly, and so that operating personnel may more easily handle assembly  10 , the handle core  14  is expanded in cross-section relative to probe core  12 . Although the handle core  14  is preferably a unitary piece of medical grade 304 stainless steel, it may be conceptually divided into a cylinder  15 , having a diameter of 4.826 mm (0.19″), and a frustum  17 . The frustum  17  tapers inwardly at 15° angle from the sides of cylinder  15 . A 600 μm (24 mil) aperture (not shown) at the narrow end of frustum  17  permits introduction of the base of probe core  12 , after which probe core  12  is joined to handle core  14 , by way of an epoxy, to form joint core  26 . The epoxy used must be conductive, so that the probe core  12  is grounded to the base core  14 , and preferably heat resistant, so that it withstands the sterilization process that the probe  10  generally should undergo in use. It must also be able to withstand the different degrees of expansion that stainless steel and tungsten undergo during the sterilization process. An epoxy that is available from Epoxy Technology, Inc. of Billerica, Mass., under the designation E3084 appears to meet these requirements. In an alternative preferred embodiment, the probe core  12  is laser-welded to the base core  14 . 
         [0026]    After joint core  26  is produced, it is dip coated with a dielectric epoxy, which has been premixed with a surfactant to promote an even coating, to form an insulating coat  30 . The desirable characteristics for an epoxy to be used are biocompatibility, heat tolerance to withstand the sterilization process, low viscosity to produce a thin film, a heat accelerated cure, and a high bulk resistivity, and a low dielectric coefficient to avoid electrical losses and withstand electrostatic charges. One epoxy that appears to meet these requirements is the epoxy #377 noted earlier. A suitable surfactant is available as FC-430 from 3M of St. Paul, Minn. Alternatively, acrylated epoxy could be used. For coat  30 , this material could have the composition, noted in Table I, below, in parts per hundred resin (PHR): 
         [0000]                            TABLE I               Substance   Proportion   Source, Contact Information                   Photomer 3015   100 PHR   Cognis Corp.,               http://www.na.cognis.com/northamerica/nacognis.html       TMPEOTA,    50 PHR   Sartomer Company, Inc., http://www.sartomer.com       (Trimethylolpropane               triacrylate SR-351)               R-812S (fumed    10 PHR   Degussa Corp., http://www.degussa.com/en/home.html       silica)               MIBK (Methyl    20 PHR   Aldrich Corp.,       Isobutyl Keytone)       http://www.sigmaaldrich.com/Brands/Aldrich.html       Darocure 1173    2.6 PHR   EM Chemicals Corp.,       (Photoinitiator)       http://www.emdchemicals.com/corporate/emd_corporate.asp                    
In an additional preferred embodiment quartz crystal, glass or a similar dielectric material is vacuum deposited to form coat  30 . In this preferred embodiment, in order to gain adherence, however, a 200 Å coat of chrome (not shown) is first applied, also through vacuum deposition on core  26  to promote the adhesion of coat  30 . The thickness of coat  30  is chosen to minimize the capacitance between core  26  and the conductive traces  50  (see below) deposited over it.
 
         [0027]    On top of coat  30 , a 0.5 μm thick plate of conductive material (not shown as such but later rendered into a set of traces  50 ) is, preferably, vacuum deposited. This plate  50  also may be adhered by way of a 200 Å layer of vacuum deposited chrome (not shown). Plating  50  must be highly conductive and, if vacuum coating is used, must be an element of the periodic table. Accordingly, gold, platinum and iridium are among the materials that may be used. Other deposition techniques, such as chemical deposition, may permit the application of other highly conductive materials, such as a conductive polymer. The material used to create plating  50  must also be susceptible to removal by laser ablating or an etching process. 
         [0028]    Next, plate  50  is sectioned into 24 longitudinal traces  50  (other numbers of traces  50  are possible) extending from approximately the tip  20  to the proximal end of base core  14 . Accordingly, near the tip  20  the traces  50  have a pitch of about 27 μm, near the base  24  have a pitch of about 80 μm at the proximal end of handle  14  have a pitch of about 630 μm. Of particular utility for performing the task of sectioning the conductive plate into traces  50  is a frequency multiplied ND:YAG laser, which can cut kerfs to separate the traces on the order of 5-10 μm width. 
         [0029]    In one preferred embodiment there are just four traces  50 . Using this embodiment a compound probing device may be built that incorporates an array of probe assemblies  10  to sense and/or stimulate a number of neural sites separated not just in depth, but also transversely to probe assembly  10  longitudinal dimension. 
         [0030]    Next, the conductive traces  50  are coated with an outer layer  60  of high coefficient dielectric material. An additional dip coat of epoxy #377 is one way of accomplishing this. As an alternative, an acrylated epoxy urethane may be used, similar to the acrylated epoxy that may be used for layer  30 , and described by Table II, below: 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE II 
               
               
                   
               
               
                 Substance 
                 Proportion 
                 Source, Contact Information 
               
               
                   
               
             
             
               
                 Photomer 3015 
                 100 PHR 
                 Cognis Corporation, 
               
               
                   
                   
                 http://www.na.cognis.com/northamerica/nacognis.html 
               
               
                 TMPEOTA, 
                  50 PHR 
                 Sartomer Company, Inc., 
               
               
                 (Trimethylolpropane 
                   
                 http://www.sartomer.com 
               
               
                 triacrylate SR-351) 
                   
                   
               
               
                 RX 03961 (acrylated 
                  32 PHR 
                 UCB Radcure, Inc., 
               
               
                 urethane) 
                   
                 http://www.chemicals.ucb-group.com/default2.html 
               
               
                 R-812S (fumed 
                  10 PHR 
                 Degussa Corp., 
               
               
                 silica) 
                   
                 http://www.degussa.com/en/home.html 
               
               
                 MIBK (Methyl 
                  63 PHR 
                 Aldrich Co., 
               
               
                 Isobutyl Keytone ) 
                   
                 http://www.sigmaaldrich.com/Brands/Aldrich.html 
               
               
                 Darocure 1173  
                  2.6 PHR 
                 EM Chemicals, 
               
               
                 (Photoinitiator) 
                   
                 http://www.emdchemicals.com/corporate/emd_corporate.asp 
               
               
                   
               
             
          
         
       
     
         [0031]    Another method is a vacuum deposition of glass or quartz crystal placed, again over an intermediate 200 Å layer of chrome. Dielectric layer  60  preferably has a thickness of from 10 to 40 um to avoid damage by static electric discharge. A laser is used to ablate this outer layer to create several apertures extending through layer  60 , having a diameter of about 10 μm at each prospective microelectrode site. A platinum-iridium electrode or neural contact site  62  is built up, preferably by electroplating, at each of these sites. Other materials that could be used for the neural contact sites  62  are platinum (not mixed with iridium), iridium, and oxidized iridium, which is also referred to as iridium black, and intrinsically conductive polymers, such as a doped polypyrrole. 
         [0032]    Base  14  is attached to a plate  70  that includes outwardly extending conductive traces (not shown) that connect traces  50  to a set of connector pins  72 . In turn, a set of connectors  72  on plate  70  attach to a matching set of connectors  74  on a circuit card assembly  80 . Assembly  80  includes a set of twenty-four circuit cards  82 , one for each trace, each bearing an identical amplification circuit for processing each signal from each trace  50  in an identical manner. 
         [0033]    The advantages of the above described preferred embodiment should now be apparent. Probe assembly  10  is strong, smooth and sleek, for moving through brain tissue to the site of interest. The cross capacitance between traces  50  is minimized due to the shape of the traces  50 , which are curved, solid rectangles, on the order of 0.5 um thick but varying between 10 um and 50 um wide. Finally, identical circuits  82  ensure equal treatment for each trace signal. 
         [0034]    An alternative preferred embodiment of a bio-probe  110  according to the present invention is shown in  FIGS. 5 and 6 . Bio-probe  110  differs from bio-probe  10  in that it is made of flexible material and defines an inner lumen  112 , for accepting a rigid insert  114 . Rigid insert  114  permits bio-probe  110  to be pushed through body tissue, for example brain tissue. Insert  114  is then removed, so that as the probe recipient moves about with the probe installed, the flexible bio-probe  110  will not tear into brain tissue, as the brain moves about slightly in the brain pan. 
         [0035]    To manufacture bio-probe  110 , a mandrel, very similar in nature to insert  114  is used. A tube  116  of flexible dielectric material, for example, polyimide is provided and fit over mandrel  114 . Tube  116  defines ten lumens  118 , the purpose of lumens  118  will be described later. The production of tube  116  may be effected by molding of polymeric resin. For example tube  116  could be produced by vacuum molding of polyimide resin. 
         [0036]    A layer of conductive material, for example gold, is then deposited by, for example, vapor deposition or sputtering. The original deposition of thin layer of conductive material may be followed by an electroplating stage, in which a thicker layer of conductive material is built up on the seed layer. 
         [0037]    Next a set of kerfs  120  are created, thereby creating a set of separated conductive traces  122 . Kerfs  120  may be formed by laser machining as noted above in reference to bio-probe  10  or through a photolithographic technique. The photolithographic technique could include a mask being pulled across a light source as bio-probe  10 , coated with photo resist, is rotated to expose different sections. Other than this rotation technique, the photolithography would be relatively standard, with either positive or negative photo resist being used, and the metal being etched away in places where the developed photo resist has been removed. 
         [0038]    Next, an additional layer  123  of dielectric material is coated over traces  122 . Apertures  132  are created to lumens  118  and apertures  134  are created to traces  122  by the use of an ND:YAG frequency multiplied laser. Finally, platinum-iridium electrodes  124  are built up in apertures  134 . These electrodes are used to stimulate brain cells and sense brain activity. Lumens  118  and apertures  134  are used in the delivery of substances, for example, a medicine or a stimulant to brain tissue. Apertures  132  and electrodes  124  can be used in tandem with a liquid substance administered through apertures  132  and the resultant effect measured by electrodes  124 . 
         [0039]    Referring to  FIGS. 7-11 , an additional preferred embodiment of a brain probe  210  is configured to be thin enough to be inserted into the brain through a canula  211  ( FIG. 8 ). The base  14  of embodiment  10  is eliminated from the design, and each trace  250  ( FIGS. 10 and 11 ) of tip portion  212  (similar in function to tip  12 ) is terminated to an insulated wire  252 . Insulated wires  252  are wrapped together and held in a grounded braided shield  246  ( FIG. 11 ) that is, in turn, contained in a stainless steel tube  254  ( FIG. 7 ) that is grounded by way of the braided shield  246 . 
         [0040]    The attachment and electrical Connection of wires  252  to the traces of tip portion  212  is a challenging operation in which delicate small scale soldering or welding must be performed. Accordingly, it is advantageous to increase the diameter of tip portion  212  as it extends from distal end  216  to proximal end  218 . A step-up extent  214  has a changing diameter in the core of the tip portion  212 . Having a step-up extent  214  in the core of the tip portion  212  appears to be the most efficient way to accommodate the need for having a very thin distal end  216 , for precise placement, and a thicker proximal end  218  for wire termination. 
         [0041]    To facilitate the termination of wires  252  to traces  250 , a wire holding ring  260  having a set of wire holding keyhole apertures  266  is used. Ring  260  is threaded onto a round hilt  264  of tip portion  212  with insulated wires held in each keyhole  266 . This permits the wires  252  to be held in place during the soldering or welding operation, greatly facilitating this operation. After the wire termination is complete, stainless steel tube  254  is slid over wires  252  and, in one preferred embodiment, terminated at ring  260 . 
         [0042]    Embodiment  210  can be adapted for use with a simian skull and brain, for research activities. Alternatively, a longer variant of preferred embodiment  210  is adapted for use on a human patient and may be used for treating Parkinson&#39;s disease, by stimulating the subthalamus nucleus  270  ( FIG. 8 ). Insulated wires  252  form a cable  272  and are connected, by way of connector  274 , to a standard amplification unit (not shown), adapted for this purpose. 
         [0043]    To use probe  210 , an aperture is created in the skull and the canula  211 , sized to accept probe  210 , is inserted. Then, probe  210  is passed through the canula  211  and into brain tissue  280 . 
         [0044]    The terms and expressions that have been employed in the foregoing specification are used as terms of description and not of limitation. The term “shield” means an electromagnetic shield. There is no intention, in the use of such terms and expressions, of excluding equivalents of the features shown and described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims which follow.