Abstract:
A microprobe for electrophysiological application, a microtube, fiber or wire probe is supported on a fixture within a tubular elastic support hose end has one end together with one end of the probe mounted on a clamping structure which is movably disposed on the fixture while the other end of the probe extends through a capillary guide tube from which its tip projects and the other end of the hose is mounted on the fixture and the hose maintained in a stretched state to engage the probe and provide radial support and a microdrive is connected to the clamping structure for axially moving the probe together with the one end of the hose and an apparatus including a plurality of independently movable probes.

Description:
BACKGROUND OF THE INVENTION 
     The present invention relates to a microprobe for electrophysiological applications with micro-fiber sensors arranged in a guide channel so as to be axially movable therein in an accurately controllable manner and an apparatus including a plurality of such microprobes. 
     In medical and in biological research and in biophysics, fine probes in the form of electrodes or pipettes are needed for many applications, wherein a body or a particular structure must be sampled or inputs must be provided in a point-by-point fashion. If the probes have a relatively large diameter they are sufficiently stable to withstand the impression reaction forces, but they have a relatively large insertion cross-section so that they can cause undesirable and possibly painful injuries. Thin probes however easily kink and it is therefore necessary to guide and support them radially or example by a tube. This however requires a quite costly drive and coupling mechanism in order to advance the probe in steps which must be shorter than the so-called kinking length of the probe. The repetitive coupling procedures then cause undesirable vibrations of the probe and sliding of the probe in the coupling structure results in additive position errors. 
     There is accordingly a need for relatively long probes with thin shafts which are safely projected from kinking. In this connection &#34;relatively long and thin&#34; means dimensions wherein shaft length to shaft diameter are at a ratio of at least 10:1. Probes in this connection are microelectrodes, chemical and electrical sensors, tubular needles, pipettes, capillaries, etc., which are to be inserted into plastic-elastic structures, particularly into nerve and muscle tissues. 
     It is an important object of the present invention to provide improved probes and probe apparatus in an economical manner, wherein the probes, on one hand, are very thin and on the other, are so stable that they can be inserted into respective structures over distances, that is, to depths, which greatly exceed the probe kinking length. Novel and highly economical guide means are to be provided which safely prevent kinking. 
     SUMMARY OF THE INVENTION 
     A microprobe for electrophysiological application, a microtube, fiber or wire probe is supported on a fixture within a tubular elastic support hose and has one end, together with one end of the probe mounted on a clamping structure which is movably disposed on the fixture while the other end of the probe extends through a capillary guide tube from which its tip projects and the other end of the hose is mounted on the fixture and the hose maintained in a stretched state to engage the probe and provide radial support and a microdrive is connected to the clamping structure for axially moving the probe together with the one end of the hose and an apparatus including a plurality of independently movable probes. 
     The preferred main support means according to the invention is an elongate elastic hose for each probe. It is engaged at its outer end by means of a clamp which preferably consists of stainless steel, extends across a guide lube and is mounted on a support fixture for the drive structure. The guide tube guides the probe in the desired insert direction. At the other, that is, its inner, end the probe and the hose which may consist, for example, of rubber, are connected by way of a clamp to a retaining pin or wire to a microdrive, by which the hose can be stretched to an exactly adjustable length. The probe tip can be accurately positioned in small advancing steps by the microdrive, that is, accurately controlled translational movement can be achieved. 
     The elastic hose keeps the probe kink-free since the radially acting kinking forces are smaller, by far, than the counteracting forces of the stretched hose, whereby the kinking length of the probe can be increased typically by 10 to 100 times. Upon stretching, the hose closely surrounds the probe and firmly engages it all around over most of its length, at least over the length thereof in which movement forces are applied thereto. Even microwaves unwound from a coil can be used for moving the probe in this manner without kinking since they are only subjected to tensional forces. Suitable hoses are generally available highly elastic silicon rubber hoses as they are used, among others, for hose pumps. 
     With such a secure hose support, relatively large axial forces can be applied to the tip of the probe which is very helpful when relatively tough structures have to be pierced. The tip insertion forces are about of the same size as the elastic axial forces applied to the rubber hose. Also, with probes which are difficult or expensive to manufacture, the penetrating force applicable to a tissue can be determined by appropriate selection of hose length and the extent to which the hoses are stretched so that neither the probe tip nor the probe shaft is damaged by the resistance of the respective tissue. 
     The inner diameter of the guide tube which may be a capillary tube is preferably about 20% larger than the probe diameter because contamination such as dust could inhibit sliding movement or even lock the probe in the guide tube; guide tubes with too large a diameter would permit undesirable side movement of the probe, for example, when the tissue provides no side support. In order to facilitate sliding movement and prevent mechanical locking of the probe in the guide tube (for example, by crystallized liquid or blood clots), the gap between the probe and the guide tube is preferably filled with a sterile lubricant such as silicon oil. This, furthermore, attenuates probe vibrations within the capillary guide tube and, as a result, reduces &#34;microphone&#34; potentials in connection with high-impedance probes. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is an axial cross-sectional view of a microprobe with its support; 
     FIG. 2 is a cross-sectional view along line II--II of FIG. 1; 
     FIG. 3 is a cross-sectional view along line III--III of FIG. 1; and 
     FIG. 4 is a perspective view of a probe apparatus with support and drive. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     FIG. 1 shows the microprobe which is designated generally by the reference numeral 10. It includes a support or fixture 12 on which a clamp 14 is mounted by screws 16 and which engages a capillary-like guide tube 18 of steel with the end 32 of a support hose 30 disposed between the clamp and the guide tube 18. The hose 30 forms a support structure for the probe 20, whose outer end 22 projects beyond the outer end 32 of the hose and is provided with a pointed tip. The inner diameter D of the capillary tube 18 of steel is about 1.2 times the outer diameter d of the probe 20 which has a slidable insulative coating 24. 
     Over the length M which includes most of the length of the probe 20, it is disposed within the passage 40 through the hose 30 by which it is firmly engaged and which forms a clamping structure 35 for the probe. Such engagement is achieved by firmly engaging the inner end 36 of the hose 30 between an inner mounting tube 38 and an outer clamping tube 48. The outer clamping tube 48 also engages a connector lead 28 which is in electrical contact with the inner end 26 of the probe 20 by means of a crimp structure. FIG. 2 shows this arrangement in cross-section. 
     An inner bushing 44 which is firmly mounted to the clamping tube 48 is connected to a pin or wire 46 which leads to a microdrive 42 (not shown in detail). The microdrive tensions the hose 30 whose clamping section 35 then stretches and firmly engages the probe 20 over its length M all around in a force-transmitting fashion. In this manner the probe 20 can be moved forward by releasing the drive wire and backward by further tensioning of the support hose for movement of the probe through the capillary guide tube 18 relative to the fixture 12--see the cross-sectional view of FIG. 3. The outer end 32 of the hose is provided with a bulge 34 which facilitates its retaining by the clamp 14. 
     The probe apparatus 50 is shown in FIG. 4 with a plurality of microprobes 10. It includes a carrier 52 which supports a group of probes 54 in a parallel guide structure 72. Again, each probe 20 is enclosed by a support hose 30 such that group 56 of support hoses is formed wherein the support hoses are individually held by clamping structures 60 which, at the same time, engage the respective connector leads 58 to the group of probes 54. Insulated wires or strings 46 are connected to the clamping structures 60 and are connected to control heads 62 which may be spools mounted on the shafts of motor drives 68 supported in motor supports 64 combined in a drive unit 66. Adjacent thereto are the probe connector leads 58. The hose group 56 is engaged at its lower end by a mounting bridge 70 wherein each hose 30 is mounted and clamped to its guide tube 18. 
     In the embodiment shown in FIG. 4 the apparatus 50 includes seven microprobes 54. The micro control heads 62 of the drive units 66 are electronically controlled and independently operable by DC drive motors 68 (with a typical transmission ratio of 1:4000). A steel cable of, for example, 200 μm diameter which is coated with polyfluorofetraethylene (Teflon) is wound on a drum of, for example, 3.5 mm diameter which is disposed on the output shaft of a transmission drive. The drive motors 68 each are provided with position sensors (not shown) which provide signals that can be stored in a computer, for example, 10 pulses per rotation of the drum which corresponds to a circumferential resolution of 0.1 μm. 
     Such a probe operating system has been used, among others, for the insertion of microelectrodes through the closed dura into the brain of permanently prepared cats and monkeys. In one embodiment a seven-channel system was employed with commercially available insulated wire probes with an outer diameter of 50 to 100 μm and quartz fiber probes with tips having points cut in two different ways; either tips with metal cores or extra cellular sensing of electrical neural signals or pipettes For the injection or for the electrophoretic introduction of compounds and for the sensing of electrical signals. 
     Recordings in the visual outer brain area were taken with a probe apparatus 50 having a group 54 of electrodes 20, which were inserted through the dura of cats and monkeys up to a depth of 20 mm. With several fiber microelectrodes 20 of, for example, 3 to 7 Ohm impedance at 1 kHz, activity potentials of single cells were recorded in a stable manner over extended periods while another probe 20 was moved forward at a speed of 1 to 10 μm/sec, that is, extremely slowly, to a position with isolated single cell activity. 
     Only little mechanical influence of the sensing position of other electrodes 20 by a moving probe is obtained as a result of easy sliding properties of the probe in the rubber hose support structure 30, the small diameter of the probes 20 and their friction-reducing coating. Consequently, interference signals are generally negligible so that the same high-impedance electrodes can measure also local slow brain activity potentials (0-150 Hz) and multiple activities during continuous electrode movement. 
     At the point of penetration the geometric arrangement of the electrodes 20 depends on the distance of the guide capillaries 18 from one another. With an outer diameter of, for example, 250 μm (inner diameter D=100 μm) a suitable distance is 500 μm. Also other, particularly smaller, distances can be achieved, for example, distances down to 200 μm, with fiber probes 20 of, for example, 70 μm probe diameter (d). Also concentric, linear or other electrode arrangements could be realized with relatively simple, known means, for example, suitable arrangement of the steel capillaries 18 or exchangeable guide structures 72 (70). With an appropriately prepared probe arrangement, the probe tips 22 can be accurately inserted into the desired areas. This is particularly advantageous if signals from two or three different brain areas have to be recorded concurrently and the probe tips 22 have to be driven for this purpose to special positions in order to analyze in the recording area the dynamic cooperation of activated nerve groups. 
     The precise mechanical drive makes a reliable probe position control by means of the rubber hose thrust movement possible. Malfunctions because of the probes getting stuck in the relatively short capillary guide tubes of steel are rare as the relatively large advancing forces of the elastic hoses 30 easily overcome the friction in the tubes. The clamping structure 35 begins immediately adjacent the inner end of the probe 26, and in this area of the hose 30, the probe 20 is firmly engaged by the hose all around so as to provide for good force transmission between the probe and the hose and also preventing kinking of the probe. Because of the continuous probe engagement (35, M), even repeated movement steps or changes in the direction of movement do not cause any added position errors since the mounting arrangement, in principle, cannot generate any error addition; if anything, only the microdrive 42 itself could cause an addition of errors, As a result, the controlled probe tip 22 will arrive at a particular desired position no matter whether the advance is performed in a single translation step or in several partial steps. 
     The rubber hose engagement permits the use of all kinds of slim probes 20 down to a probe shaft diameter of about d≈25 μm. With even smaller probes, handling may become difficult. It is possible to use electrodes for the electrical stimulation and for the sensing of neural and muscle signals as well as recording, and injection pipettes and acupuncture needles. (Larger diameter probes, for example, with 200 μm outer diameter and above can also be used but they are usually strong enough so that they can be operated by known drive arrangements.) Depending on the shaft diameter d of the probes 20 it is advisable to exchange the capillary guide tubes of steel which can be done rapidly. 
     When compared with prior art drive arrangements for fiber microelectrodes, the arrangement according to the invention has additional advantages. The guide system (30, 20) is much smaller and lighter and it is easier and less expensive to manufacture than the prior art manipulators. It also can be used in connection with very fine probes 20 so that little space is displaced in the tissue being penetrated and little damage is caused. No cumulative position errors occur either. Smooth accurate movement of the probes with relatively large penetration depths can be achieved. The arrangement causes hardly any error signals of mechanical origin and also is not subject to such errors. Furthermore, the arrangement can use any of a large number of commercially available microdrives. A good number of such small probes 20 can be provided in a compact group 54 and they can be independently controlled in spite of their small distance from one another. 
     The present invention is not limited to the arrangements described in detail; it can, particularly, also be utilized for macro technical applications. It is noted however, that, for a preferred embodiment of a microprobe 10 for electro physiological applications, at least one microtube, fiber or wire-like probe 20 is slidably disposed within a guide hose 30 so as to be movable relative to the fixture 12 supporting the arrangement. The hose 30 surrounds the major portion M of the probe 20 in a clamping structure 35 which is movable by means of a microdrive 42. The clamped hose end 32 is provided with a bulge 34 so that the hose end can be safely retained by the clamp 14. The inner end 26 of the probe is in contact with a connector lead 28, within a mounting tube 38, which extends from the mounting tube 38 and is surrounded by an outer clamping tube 48 engaging the inner end 36 of the hose and also the connector lead 28. The outer clamping tube 48 is connected lo the microdrive 42. The hose 30 comprises silicone rubber. The probe 20 is provided with a slidable insulative coating at least on its main portion M. A probe apparatus includes supported on a carrier 52 a group of probes 54 which is movable via a group of hoses 56 by means of control heads 62. The hoses 30 arranged in the group 56 in close side-by-side relationship ere engaged by 8 mounting bridge 70 where the guide tubes are mounted to the hoses and from where the guide tubes extend through 8 parallel-guide structure 72 and project slightly therefrom with the probes extending from the guide tubes and being independently movable by stretching of the respective hoses or releasing them by movement of the respective clamping tubes 48. 
     All features covered by the claims and presented in the description and the drawings, with the advantages described, and with the various design features and spatial arrangements are considered to be inventive either alone or in the various combinations.