Abstract:
An apparatus for use in neurophysiological research and clinical diagnosis comprises a hollow body having a plurality of electrode wires slidably carried therein. Each electrode wire is carried on a shuttle that is slidably mounted in a slot in an interior wall of the hollow body.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
   This application claims benefit of U.S. Provisional Ser. No. 60/698,755 filed Jul. 13, 2005. 

   FIELD OF THE INVENTION 
   This invention relates generally to multi-electrode microdrive arrays. The invention has particular utility in connection with implantable micro-electrode microdrive arrays for use with brain research instruments, and will be described in connection with such utility, although other utilities are contemplated. 
   BACKGROUND OF THE INVENTION 
   Implantable independently adjustable electrodes are used for in vivo and in vitro neurophysiological research. Prior art brain research instrumentation includes movable single channel or single electrode mechanisms which were limited to recording from single locations in the brain. Early research tended to be concentrated in sensory portions of the brain such as the visual cortex. For example, the research would seek to identify what particular stimulus in the subject&#39;s visual field would cause an individual neuron in the visual cortex to fire. The prior art single electrode mechanisms were capable of being moved to different locations in the brain but were only capable of recording from a single neuron or a small neuron cluster at a time. 
   The prior art also includes apparatus with multiple electrodes whose position in space is fixed relative to the other electrodes. These prior art electrodes are capable of recording timing or firing patterns of multiple neurons or multiple small clusters of neurons. The importance of being able to record timing patterns is critical to understanding higher order functions of the brain. However, the multi-channel or multi-electrode prior art devices could only be used in restrained animal subjects and were not capable of being moved within the brain. Thus, the timing patterns that could be recorded within the brain were limited by the number of electrodes and to only those patterns that occurred between the individual neurons or small neuron clusters that happen to be near the tips of the recording electrodes. Another disadvantage of the fixed array of electrodes is that the research is inherently limited to those brain functions performed by a non-moving subject. 
   The foregoing discussion of the prior art derives largely from U.S. Pat. No. 5,928,143 (the &#39;143 patent) in which there is described an implantable multi-electrode microdrive array that may be made sufficiently small and light weight and it may be implanted on animals as small as rats. Referring to  FIGS. 1-3 , the multi-electrode microdrive array made in accordance with the &#39;143 U.S. patent comprises an array of elongated guide cannulae referred to generally as  20  which provide a guide means for the recording electrodes. In the embodiment shown the total number of guide cannulae provided is 14. The 14 cannulae and their associated drive mechanisms are identical. Each of the guide cannulae, such as individual cannula  21  shown in  FIG. 1 , has an upper end  21   a  and a lower end  21   b . The lower ends of each cannula are aligned parallel with and are adjacent each other. The 14 guide cannulae, shown in the embodiments of  FIGS. 1 and 2 , easily fit into a passageway  8  formed in the skull  9  of the subject animal. 
   The upper end  21   a  of cannula  21  is inclined outwardly from the central vertical axis A of the apparatus  10  by preferably an angle of 30°. Other angles may be used. By inclining the upper ends of the array of cannulae  20  outwardly, as shown best in  FIG. 2 , sufficient spacing is obtained between adjacent cannulae that electrodes carried within the cannulae are capable of being independently adjusted relative to one another. 
   A support means  40  is provided for the array of guide cannulae  20 . The support means is preferably a mechanical plastic core. The plastic core has an upper end  42  and a lower end  43 . A first passageway  44  is formed in the lower end  43  of the plastic core, and is adapted to receive a cylindrical bushing  49  with an internal passageway  48  through which the lower ends of the array of guide cannulae  20  extend, as shown in  FIG. 3 . The support means or plastic core  40  also has a plurality of inclined passageways such as  46  formed in its upper portion  42  for each upper portion of each guide cannula. Each of the inclined passageways such as  46  communicates with the passageway  48  formed by bushing  49  and extends upwardly and preferably outwardly at an angle of 30° of the vertical axis A. Each of the guide cannulae remains fixed relative to support means  40  with upper end  21   a  terminating just below the upper surface  42   a  of support means  40 . 
   Each of said guide cannulae in the array  20  carries one or more electrodes. For example, guide cannula  21  shown in  FIG. 1  carries in the preferred embodiment a group of four electrodes  51 , which is referred herein as a tetrode. The tetrode  51  has an upper end  51   a  which is located in the upper portion  21   a  of guide cannula  21 . The tetrode  51  has a lower portion  51   b  which is capable of being moved downwardly into the brain  7  to various depths. 
   According to the &#39;143 patent, the preferred electrode assembly includes a tetrode which comprises four recording probes made by twisting together four strands of polyamide-coated, 14 micron diameter, nichrome wires. To obtain adherence and stiffness, the insulation is briefly softened by heating, while the wires are under tension, and then allowed to cool. Wires are cut flat at the same level and each tip is gold-plated separately to reduce the impedance of individual electrodes to 400-500 K-ohm. The overall diameter of each tetrode is approximately 40 microns. The tetrode is mounted and glued into two nested polyamide tubes, those tubes being 78 and 110 microns outside diameter, respectively, which are then mounted in the support means  40 . The smaller tubing (78 micron O.D.) forms each guide cannula  21  and the larger tubing (110 micron O.D.) forms each drive cannula  71 . 
   Electrode adjustment means shown generally as  70  ( FIG. 1 ) are connected to the upper end of each electrode and each guide cannula. The electrode adjustment drive means  70  is capable of moving the electrode or electrode bundle in each guide cannula independently of the electrodes carried in the other guide cannulae in the array  20 . As shown in  FIG. 1 , each electrode adjustment means  70  is capable of moving between the position shown in solid lines downwardly to the position shown in phantom as  70   a . Electrode adjustment means  70  in the preferred embodiment shown in  FIG. 1  includes a drive cannula  71  slidably mounted over the upper end  21   a  of guide cannula  21 , electrode drive means  75 , adjustment rod  72  and guide rod  85  described below. Each guide cannula  21  (typically 78 micron O.D.) slidably nests in drive cannula  71  (typically 110 micron O.D.). The top of electrode  51   a  slides through and is attached to the top of drive cannula  71  by glue. A plurality of adjustment rod means  72  ( FIG. 3 ) are provided, each of which is carried by support means  40  and each of which is mounted parallel to its respective guide cannula  21 . Adjustment rod means  72  is preferably an 0.080″ headless stainless screw, threaded into support means  40 . 
   Referring also to  FIGS. 4   a  and  4   b , an electrode drive means  75  is carried by each adjustment rod  72  as shown best in  FIG. 3 . Electrode drive means  75  includes a cylindrically shaped nut  76  with a threaded inner bore  77  which threads onto threaded rod  72 . Nut  76  has a turning slot  78  formed in its upper surface. 
   Nut  76  is connected to a generally triangular shaped bridge  80 . Bridge  80  has a first bore  81  formed therein for carrying drive cannula  71 . Nut  76  has an upper flange  76   a  and a lower flange  76   b  which cause bridge  80  to move upwardly and downwardly on rod  72  as the nut  76  is turned. Bridge  80  has a second bore  82  formed therein for receiving a guide rod  85  ( FIG. 2 ). Guide rod  85  prevents rotation of bridge  80  relative to adjustment rod  72  as nut  76  is rotated. Guide rod  85  is parallel to adjustment rod  72  and is cemented into support means  40 . 
   Referring also to  FIGS. 5   a - 5   c , an electrode adjustment tool  100  is provided having a hollow drive sleeve  101  adapted to slide over the top of adjustment rod  72  ( FIG. 3 ). A drive tip  102  is formed at the distal end  103  of sleeve  101 . Drive tip  102  engages turning slot  78 . A turning knob  105  is carried near the proximal end  104  of sleeve  101  and carries a scale  108  to indicate the motion imparted to an electrode. Rotation of knob  105  imparts axial motion to drive cannula  71  and to the electrode or electrodes  51  carried within that drive cannula. 
   While the multi-electrode microdrive array described in the aforesaid &#39;143 patent provides significant improvements over prior art devices in providing an increased number of independently adjustable recording electrodes in an array that is small enough and light weight enough to be easily carried on the skull of the subject animal, while providing free motion of the subject, the multi-electrode microdrive array of the &#39;143 patent is expensive to manufacture requiring painstaking and time consuming machining and assembly. The multi-electrode microdrive array of the &#39;143 patent also is difficult to use in the field requiring painstaking and time consuming manipulation to adjust individual electrodes into position. 
   BRIEF DESCRIPTION OF THE INVENTION 
   The present invention overcomes the aforesaid and other disadvantages of prior art multi-electrode microdrive arrays including multi-electrode microdrive arrays made in accordance with the &#39;143 patent by providing a multi-electrode microdrive array in which electrode wires are supported by shuttles which in turn are slidably mounted in slots formed in a support. In a preferred embodiment of the invention, the electrode wires are carried within capillary tubing. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Further features and advantages of the present invention will be seen from the following detailed description, taken in connection with the accompanying drawings, wherein like numerals depict like parts, and wherein: 
       FIG. 1  is a sectional view of apparatus made in accordance with the prior art shown schematically as attached to the skull of a laboratory animal; 
       FIG. 2  is a top perspective view of the apparatus of claim  1 , and shows how the electrode adjustment mechanisms are mounted relative to each other; 
       FIG. 3  is a sectional view on the line  3 - 3  of  FIG. 2 ; 
       FIGS. 4   a  and  4   b  are a top and side elevational view, respectively, of the electrode adjustment mechanism of the apparatus of  FIG. 1 ; 
       FIG. 5   a  is a side elevational view of a prior art electrode adjustment tool for the apparatus of  FIG. 1 ; 
       FIG. 5   b  is a section on the line  5 - 5  of  FIG. 5   a;    
       FIG. 5   c  is a top end view of the tip of the adjustment tool of  FIG. 5   a;    
       FIG. 6  is a perspective view and  FIG. 6   a  an exploded view of a multi-electrode microdrive array apparatus made in accordance with a preferred embodiment of the present invention; 
       FIG. 7  is a top plan view and  FIG. 7   a  a perspective view of the main body portion of the apparatus of  FIG. 6 ; 
       FIG. 8  is a top plan view and  FIG. 8   a  a perspective view of a shuttle part of the apparatus of  FIG. 6 ; 
       FIG. 9  is a top plan view and  FIG. 9   a  is a perspective view of a top guide ring part of the apparatus of  FIG. 6 ; 
       FIG. 10  is a top plan view and  FIG. 10   a  is a perspective view of a bottom guide ring part of the apparatus of  FIG. 6 ; 
       FIG. 11  is a side elevational view showing portions of the shuttle and guide part of the apparatus of the present invention; 
       FIG. 12  is a bottom plan view of a portion of the apparatus of the present invention; and 
       FIG. 13  is a view similar to  FIG. 6   a  of an alternative multi-electrode microdrive array apparatus made in accordance with the present invention. 
       FIG. 14  is an exploded view of a multi-electrode microdrive array apparatus according to yet another embodiment of the present invention; 
       FIG. 15  is a top plan view and  FIG. 15   a  is a perspective view of a drive body part of the apparatus of  FIG. 14 ; 
       FIG. 16  is a top plan view and  FIG. 16   a  is a perspective view of a drive tip part of the apparatus of  FIG. 14 ; 
       FIG. 17  is a top plan view and  FIG. 17   a  is a perspective view of an inner drive cap part of the apparatus of  FIG. 14 ; 
   

   DETAILED DESCRIPTION OF THE INVENTION 
   Referring to  FIGS. 6-10  a multi-electrode microdrive array apparatus  200  made in accordance with the present invention comprises a two piece lower shroud or casing  202 ,  204 . Shroud  204  is stepped down at its distal end  206  and sized to easily fit within a passageway (not shown) formed in the skull in a subject animal. Referring also to  FIGS. 10 and 10   a , a lower guide ring  208  is mounted to the top of shroud  202 . Lower guide ring  208  includes a plurality of through holes  210  for accommodating the distal ends of adjustment screws  212  and a second plurality of holes  214  which act as guides for individual electrodes or electrode assemblies as will be described in detail hereinafter. An alignment channel  216  is formed in a wall of the lower guide ring  208  for accommodating a boss  218  formed in an outer wall of main body  220 . 
   Body  220  is cylindrical in shape, and includes a plurality of key hole shaped slots  222  for accommodating shuttles  240  and adjustment screws  212  as will be described in detail hereinafter. A top guide ring  226  is fitted over the top of body  220  and includes a plurality of adjustment screw holes  228 . Top guide ring  226  also includes a channel  230  for accommodating boss  218 . As will be appreciated, channels  216  and  230  and boss  218  ensure precise alignment of guide ring  208 , body  220  and top guide ring  226 . Thus, holes  210  and  228  will be precisely aligned over one another, and aligned with the rounded heads of slots  222 . A circuit board support ring  232  is mounted above top guide ring  226 , and carries a plurality of circuit boards  234 . Circuit board support ring  232  also includes a plurality of adjustment screw holes  233  which are aligned with holes  228  and holes  214 . Circuit board support ring  232  is aligned with top guide ring by driving screws (not shown) through holes  235  and  227  pre-formed in the circuit board support ring  232  and top guide ring  226 , respectively. 
   A removable cover  238  completes the outer casing. 
   Referring in particular to  FIGS. 8 and 8   a , a key shaped shuttle  240  is slidably mounted in slot  222 , one shuttle per slot. Slots  222  may be formed by milling or may be molded in. Each shuttle includes a through threaded through-hole  242  sized to accommodate an adjustment screw  212 , and a second through hole  244  sized to accommodate a wire electrode  246 . In a preferred embodiment of the invention, each wire electrode  246  is threaded through a capillary tubing  248  having an OD just slightly smaller than the ID of hole  244  so that the capillary can be threaded into hole  244  and held in position by friction. In a preferred embodiment of the invention, the capillary tubing comprises fused silica tubing available from Poly Micro Technologies, LLC of Phoenix, Ariz. 
   In use, the multi-electrode microdrive array is mounted to the skull of a test animal, and shuttles  240  carrying capillary tubing and electrodes  246  are pushed through holes  205  formed through the bottom wall of shroud  204  as will be discussed below, and advanced so that their distal ends are located in a desired position by adjusting screws  212 . 
   A feature and advantage of the present invention over the prior art multi-electrode drive array apparatus results from the use of capillary tubing surrounding the electrodes. The capillary tubing exhibits a combination of stiffness, flexibility and lack of bending memory to allow a free-form, unsupported consistent movement of the electrode from the shuttle, through holes  205  formed through the bottom wall of shroud  204 , and permits off-axis driving of unsupported capillary tubing without complicated mechanical guides (see  FIG. 11 ). This in turn allows the electrode exit pattern to be independently placed (user defined). This also permits tight electrode spacing (see  FIG. 12 ). 
   Another feature and advantage of the present invention over prior art multi-electrode microdrive array apparatus such as described in the &#39;143 U.S. patent is the significantly reduced number of parts as compared to the &#39;143 patented apparatus. As a result, manufacturing and assembly costs are substantially reduced. Also, the reduced number of parts permits a greater number of electrodes to be packed into a base. 
   The invention is susceptible to modification. For example, while a single circle of shuttles is shown, it is possible to load a second, smaller diameter multi-electrode microdrive array shown generally at  250  in the central hollow space  252 . This is illustrated in  FIG. 13 . 
   Another embodiment of the invention is shown in  FIGS. 14-17 . This embodiment is similar in function but is smaller and has mass and fewer parts. In this configuration, the invention will be cheaper to manufacture and less of a nuisance to the subject animal. 
   According to this latter embodiment, the lower shroud or casing and the lower guide ring of the previously described embodiments have been combined into a single part as the drive tip  304 . The drive tip  304  contains a distalmost end  306 , sized to fit into a passageway created in the skull of the subject animal; an alignment guide  316  used to align the drive body  320 ; and a plurality of holes to accept the distal end of adjustment screws  312 . The adjustment screws  312  operate in the same manner as the adjustment screws  212  in the above described embodiments. 
   The drive body  320  of this latter embodiment functions identical to the main body  220  of the above described embodiments except for the fact that drive body  320  is smaller and contains fewer keyhole shaped slots  322 . The shuttles  340  operate in the same manner as the shuttles  240  in the above discussed embodiments. A lower alignment boss  318  aligns with the alignment channel  316  of the drive tip  304  such that the holes  310  are perfectly aligned with the center of the keyhole shaped slots  322 . The drive body  320  also contains a number of holes  350  that are present to reduce the amount of material in the drive body, consequently reducing weight of the apparatus. 
   Two upper alignment bosses  360  protrude horizontally from the upper end of the drive body  320 . These upper alignment bosses  360  of the drive body  320  contain two sets of holes used to align the inner drive cap  332  and the end cap  338 . The inner set of holes  362  of the upper alignment bosses align with holes in two alignment bosses of an inner drive cap  330 . These are aligned such that holes  328  in the inner drive cap  330  align with the slots  322  of the drive body  320  and the holes  310  of the drive tip  304 . A circuit board ring  332  attaches to the top of the inner drive cap  330 . Finally, a removable cover  338  is provided. 
   Still other changes may be made without departing from the spirit and scope of the invention.