Abstract:
A catheter has a cooling distal section for freezing tissue to sub-zero temperatures with one or more miniature reverse thermoelectric or Peltier elements, also referred to herein as micro-Peltier cooling (MPC) units or electrodes. The MPC units may be on outer surface of an inflatable or balloon member or a tip electrode shell wall that has a fluid-containing interior cavity acting as a heat sink. Each MPC unit has a hot junction and a cold junction whose temperatures are regulated by the heat sink, and a voltage/current applied to the MPC units. A temperature differential of about 70 degrees Celsius may be achieved between the hot and cold junctions for extreme cooling, especially where the MPC units include semiconductor materials with high Peltier co-efficients. An outer coating of thermally-conductive but electrically-insulative material seals the MPC units to prevent unintended current paths through the MPC units.

Description:
FIELD OF INVENTION 
       [0001]    This invention relates to electrophysiologic (EP) catheters, in particular, EP catheters for mapping and/or ablation in the heart. 
       BACKGROUND 
       [0002]    Many medical procedures are performed using minimally invasive surgical techniques wherein one or more slender implements are inserted through one or more small incisions into a patient&#39;s body. With respect to ablation, the surgical implement may include a rigid or flexible structure having an ablation device at or near its distal end that is placed adjacent to the tissue to be ablated. Radio frequency energy, microwave energy, laser energy, extreme heat, and extreme cold may be provided by the ablation device to destroy the tissue. 
         [0003]    With respect to cardiac procedures, cardiac arrhythmia may be treated through selective ablation of cardiac tissue to eliminate the source of the arrhythmia. A popular minimally invasive procedure, radio frequency (RF) catheter ablation, includes a preliminary step of conventional mapping followed by the creation of one or more ablated regions (lesions) in the cardiac tissue using RF energy. Multiple lesions are frequently required. Often, five lesions, and sometimes as many as twenty lesions may be required before a successful result is attained. Sometimes only one of the lesions is actually effective. 
         [0004]    Deficiencies of radio frequency ablation devices and techniques have been to some extent overcome by cryogenic mapping and ablation. Such cryogenic mapping techniques are in U.S. Pat. Nos. 5,423,807; 5,281,213 and 5,281,215. However, even though combined cryogenic mapping and ablation devices often times permit greater certainty and less tissue damage than RF devices and techniques, both cryogenic and RF ablation devices are usually configured for spot or circular tissue ablation. 
         [0005]    Spot tissue ablation is acceptable for certain procedures. However, other procedures may be more therapeutically effective if multiple spot lesions are made simultaneously, such as in a circumferential pattern in a tubular region and/or the ostium thereof. In that regard, catheters with inflatable assemblies or balloons are known. Such balloons may include electrodes positioned on the outer surface of the balloons for ablating tissue and are typically inflated with a pressurized fluid source. With cryoablation, reversible freezing of tissue occurs at a temperature of about −10 C (about +14 F), and permanent tissue ablation occurs at a temperature of about −73 C (about −99.4 F). However, where cooling fluids are passed through the cryogenic catheter while inside a patient&#39;s body, the use of sub-freezing coolants may not be ideal. 
         [0006]    Accordingly, a need exists for a cryoablation catheter having an inflatable member or balloon, with significantly improved cooling efficiency yet reduced risks of health hazards to the patient and attending physicians and assistants from exposure to or contact with sub-freezing coolants. 
       SUMMARY OF THE INVENTION 
       [0007]    Features of the present invention include a catheter having a cooling distal section for freezing heart tissue to sub-zero temperatures with one or more miniature reverse thermoelectric or Peltier elements, also referred to herein as micro-Peltier cooling (MPC) units or electrodes. The MPC units may be provided on an outer surface of a distal section member of the catheter, such as an inflatable or balloon member or a shell wall that can advantageously provide an interior cavity which can contain fluid so as to function as a heat sink for the MPC units. Each MPC unit has a hot side/junction and a cold side/junction whose temperatures are regulated by the heat sink, and a voltage/current applied to the one or more MPC units. A temperature differential of about 70 degrees Celsius may be achieved between the hot and cold sides/junctions for extreme cooling of tissue via contact with or exposure to the cold sides of the one or more MPC units, especially where the MPC units include semiconductor materials with high Peltier co-efficients. The MPC units may be arranged in a variety of patterns on the contact surface. An outer coating of thermally-conductive but electrically-insulative material seals the one or more MPC units against exposure to blood and other conductive tissue or fluids which may cause unintended current paths through the MPC units. 
         [0008]    Embodiments of the present invention include an electrophysiology catheter for use in a patient&#39;s vasculature, comprising an elongated catheter body and a distal section having a micro-Peltier cooling (MPC) unit. The MPC unit has a hot junction and a cold junction, a thermally-conductive and electrically-nonconductive layer on the cold junction sealing the cold junction from exposure to blood in the vasculature, and a thermally-conductive and electrically-nonconductive substrate supporting the MPC unit, wherein the hot junction is in closer proximity to the substrate and the cold junction is in closer proximity to the layer. The distal section also has an interior cavity configured to receive a fluid having a predetermined temperature, wherein the cavity is configured to position the fluid for thermal conduction between the fluid and the hot junction across the substrate. The catheter is configured for current flow through the cold and hot junctions of the MPC unit. 
         [0009]    In some detailed embodiments, the current flows from a first N-type semiconductor to a last P-type semiconductor. 
         [0010]    In some detailed embodiments, the distal section includes an inflatable balloon member having a membrane defining the interior cavity, wherein at least a portion of the membrane forms the substrate. 
         [0011]    In some detailed embodiments, the distal section includes a distal tip shell having a shell wall defining the interior cavity, wherein at least a portion of the shell wall forms the substrate. 
         [0012]    In some detailed embodiments, the cold junction includes an electrically-conductive material, preceded by an N-type semiconductor material, and followed by a P-type semiconductor material, connected in series. 
         [0013]    In some embodiments, the hot junction includes an electrically-conductive material, preceded by P-type semiconductor material, and followed by an N-type semiconductor material, connected in series. 
         [0014]    In some embodiments, the P-type semiconductor material comprises bismuth telluride, silicon-germanium and/or bismuth-antimony. 
         [0015]    In some embodiments, the N-type semiconductor material comprises bismuth telluride, silicon-germanium and/or bismuth-antimony. 
         [0016]    In some embodiments, the temperature of the fluid ranges between about 10 C degrees Celsius and −10 degrees Celsius. 
         [0017]    In some embodiments, the catheter further comprises a control handle and a voltage/current source providing the current flow is housed in the control handle. 
         [0018]    Other embodiments of the present invention include an electrophysiology catheter for insertion into a patient&#39;s vasculature, comprising an elongated catheter body, a distal section distal of the catheter body, the distal section having an outer surface layer configured for contact with tissue, the contact surface layer being thermally conductive and electrically nonconductive, a control handle proximal of the catheter body, and a micro-Peltier cooling (MPC) unit. The MPC units has a first wire of a first material having a distal end in the distal section, and a proximal end proximal of the distal section, and a second wire of a second material having a distal end in the distal section, and a proximal end proximal of the distal section. The MPC unit also has a cold junction comprising an electrically conductive connection of the distal ends of the first and second wires, wherein the cold junction is positioned in the distal section and thermally coupled to the outer surface layer, and a hot junction comprising an electrically conductive connection of the proximal ends of the first and second wires, wherein the hot junction is positioned proximally of the cold junction. The MPC unit further has a heat sink thermally coupled to the hot junction, wherein the heat sink having a predetermined temperature, wherein the catheter is configured for current flow through the MPC unit. 
         [0019]    In some detailed embodiments, the distal section includes a distal needle thermally coupled to the cold junction, and an outer surface layer of the distal needle provides the outer surface layer. 
         [0020]    In some detailed embodiment, the hot junction is proximal of the control handle. 
         [0021]    In some detailed embodiments, the heat sink includes a fluid reservoir. 
         [0022]    In some detailed embodiments, the predetermined temperature of the heat sink ranges between about 10 degrees Celsius and −10 degrees Celsius. 
         [0023]    In some detailed embodiments, the first material includes an N-type semiconductor material comprising bismuth telluride, silicon-germanium and/or bismuth-antimony. 
         [0024]    In some detailed embodiments, the first material includes a P-type semiconductor material comprising bismuth telluride, silicon-germanium and/or bismuth-antimony. 
         [0025]    Further embodiments of the present invention include an electrophysiology catheter for insertion into a patient&#39;s vasculature, comprising an elongated catheter body, and a distal section distal of the catheter body, wherein the distal section has a distal probe portion with an outer surface layer configured for tissue contact and the outer surface layer is thermally-conductive and electrically-nonconductive. The catheter also includes a control handle proximal of the catheter body, and a micro-Peltier cooling (MPC) unit. The MPC unit has a first wire of a first material having a distal end in the distal section, and a proximal end proximal of the distal section, and a second wire of a second material having a distal end in the distal section, and a proximal end proximal of the distal section. The MPC unit further has a cold junction and a hot junction. The cold junction comprises an electrically-conductive material in a tubular configuration forming the distal probe portion, the electrically-conductive material couples the distal ends of the first and second wires, and the cold junction is thermally coupled to the outer surface layer. The hot junction comprises an electrically conductive connection of the proximal ends of the first and second wires, wherein the hot junction is positioned proximally of the cold junction. The MPC unit also includes a heat sink thermally coupled to the hot junction, wherein the heat sink has a predetermined temperature. 
         [0026]    In some detailed embodiments, the first material includes an N-type semiconductor material comprising bismuth telluride, silicon-germanium and/or bismuth-antimony. 
         [0027]    In some detailed embodiments, the first material includes a P-type semiconductor material comprising bismuth telluride, silicon-germanium and/or bismuth-antimony. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0028]    These and other features and advantages of the present invention will be better understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein: 
           [0029]      FIG. 1  is a top plan view of a catheter of the present invention, having an inflatable cryoablation assembly, according to an embodiment. 
           [0030]      FIG. 2  is a schematic representation of the electrode assembly of  FIG. 1 , inflated and positioned in or near an ostium of a pulmonary vein. 
           [0031]      FIG. 3  is an end cross-sectional view of a catheter body  12 , according to an embodiment of the present invention. 
           [0032]      FIG. 4  is an end cross-sectional view of an intermediate deflection section, according to an embodiment of the present invention. 
           [0033]      FIG. 5A  is a detailed perspective view of the inflatable cryoablation assembly of  FIG. 1 , with one or more Micro-Peltier Cooling (“MPC”) modules. 
           [0034]      FIG. 5B  is a perspective view of an inflatable cryoablation assembly, according to another embodiment of the present invention. 
           [0035]      FIG. 6  is a side cross-sectional view of an MPC module, according to an embodiment of the present invention. 
           [0036]      FIG. 7  is a block diagram of a circuit for the inflatable cryoablation assembly, according according to an embodiment of the present invention. 
           [0037]      FIG. 8  is a block diagram of a circuit for the inflatable cryoablation assembly, according to another embodiment of the present invention. 
           [0038]      FIG. 9  is a perspective view of a distal end of a focal cryoablation catheter, according to according to an embodiment of the present invention. 
           [0039]      FIG. 10  is a perspective view of a distal end of a focal cryoablation catheter, according to another embodiment of the present invention. 
           [0040]      FIG. 11  is a perspective view of a distal end of a focal cryoablation catheter, according to another embodiment of the present invention 
           [0041]      FIG. 12  is a side cross-sectional view of a distal end of a focal cryoablation catheter, according to an embodiment of the present invention. 
           [0042]      FIG. 13  is a perspective view of a distal end of a focal cryoablation catheter, having one MPC unit, according to an embodiment of the present invention. 
           [0043]      FIG. 14A  is a side cross-sectional view of the distal end of  FIG. 13 . 
           [0044]      FIG. 14B  is a schematic representation of the circuit of the MPC unit of  FIG. 13 , according to an embodiment of the present invention 
           [0045]      FIG. 14C  is a side cross-sectional view of a distal end of a focal cryoablation catheter, according to another embodiment. 
           [0046]      FIG. 15A  is a perspective view of a “cold” junction having a layered construction. 
           [0047]      FIG. 15B  is a perspective view of the layered construction of  FIG. 15A  being rolled into a cylindrical body. 
           [0048]      FIG. 16  is a side cross-sectional view of a distal tip of a catheter including the “cold” junction cylindrical body of  FIG. 16B . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0049]    As shown in  FIG. 1 , a catheter  10  comprises an elongated catheter body  12 , a distal section having an inflatable cryoablation assembly  13  with a balloon member  24  and one or more micro-Peltier cooling modules  15  in and/or on its outer surface, and a deflection control handle  16  attached to the proximal end of the catheter body  12 . The catheter  10  may function in combination with a further distal electrode assembly, for example, a lasso electrode assembly  17 , for which the inflatable assembly  13  can function as an anchor and/or stabilizer when the lasso electrode assembly  17  is in use, such as when inserted in a pulmonary vein PV of the left atrium, as shown in  FIG. 2 . 
         [0050]    The catheter body  12  comprises an elongated tubular construction, having a single, axial or central lumen  18 , as shown in  FIG. 3 . The catheter body  12  is flexible, i.e., bendable, but substantially non-compressible along its length. The catheter body  12  can be of any suitable construction and made of any suitable material. A presently preferred construction comprises an outer wall  22  made of a polyurethane, or PEBAX. The outer wall  22  comprises an imbedded braided mesh of high-strength steel, stainless steel or the like to increase torsional stiffness of the catheter body  12  so that, when the control handle  16  is rotated, the tip section  14  of the catheter  10  will rotate in a corresponding manner. 
         [0051]    The outer diameter of the catheter body  12  is not critical, but is preferably no more than about 8 french, more preferably about 7 french. Likewise the thickness of the outer wall  22  is not critical, but is thin enough so that the central lumen  18  can accommodate components, including, for example, one or more puller wires, electrode lead wires, irrigation tubing, and any other wires and/or cables. The inner surface of the outer wall  22  is lined with a stiffening tube  20 , which can be made of any suitable material, such as polyimide or nylon. The stiffening tube  20 , along with the braided outer wall  22 , provides improved torsional stability while at the same time minimizing the wall thickness of the catheter, thus maximizing the diameter of the central lumen  18 . The outer diameter of the stiffening tube  20  is about the same as or slightly smaller than the inner diameter of the outer wall  22 . Polyimide tubing is presently preferred for the stiffening tube  20  because it may be very thin walled while still providing very good stiffness. This maximizes the diameter of the central lumen  18  without sacrificing strength and stiffness. As would be recognized by one skilled in the art, the catheter body construction can be modified as desired. For example, the stiffening tube can be eliminated. 
         [0052]    The intermediate deflection section comprises a shorter section of tubing  19 , which as shown in  FIG. 4 , has multiple lumens, for example, off-axis lumens  31 ,  32 ,  33  and  34 . In some embodiments, the tubing  19  is made of a suitable non-toxic material more flexible than the catheter body  12 . A suitable material for the tubing  19  is braided polyurethane, i.e., polyurethane with an embedded mesh of braided high-strength steel, stainless steel or the like. The outer diameter of the deflection section  14  is similar to that of the catheter body  12 . The size of the lumens is not critical and can vary depending on the specific application. 
         [0053]    Various components extend through the catheter  10 . In some embodiments, as shown in  FIG. 3  and  FIG. 4 , the components include one pair of lead wires  28  and  29  for each micro-Peltier cooling module  15 . The components also include one or more puller wires  26  and  27  for deflecting the deflection section  14 , a cable  44  for an electromagnetic position sensor  46  (not shown) housed in suitable location in a distal portion of the catheter. The components further include a feeder fluid tubing  38  for passing fluid distally along the catheter and into the balloon member  24  for inflation and cooling, a return fluid tubing  39  for passing fluid from the balloon member proximally along the catheter, and a guidewire tubing  45 . These components pass through the central lumen  18  of the catheter body  12 , as shown in  FIG. 3 . 
         [0054]    It is understood that a return fluid tubing is optional where fluid is used for balloon member inflation purposes during procedures of shorter duration, for example, about 10 mins or less. For procedures of longer duration, the feeder fluid tubing  38  and the return fluid tubing  39  enable circulation of the fluid within the balloon member to maintain efficacy of cryogenic cooling of the micro-Peltier modules. 
         [0055]    In the deflection section  14 , different components pass through different lumens of the tubing  19  as shown in  FIG. 4 . In some embodiments, the lead wires  28  and  29  and cable  44  for electromagnetic position sensor  46  pass through first lumen  31 . The first puller wire  26  passes through second lumen  32 . The feeder fluid tubing  38  passes through third lumen  33 . The return fluid tubing  39  passes through a fourth lumen  34 . A second puller wire  27  passes through fifth lumen  35 . The guidewire tubing  45  passes through a sixth lumen  43 . The second and fifth lumens  32  and  35  are diametrically opposite of each other to provide bi-directional deflection of the intermediate deflection  14 . 
         [0056]    The distal ends of the puller wires  26  and  27  can be attached to sidewall of the tubing  19  at or near its distal end, for example, with the use of T-bars, as known in the art. Such a design is described in U.S. Pat. No. 9,101,733, the entire disclosure of which is incorporated herein by reference. Each puller wire  26  and  27  is anchored at its proximal end in the control handle  16 . In some embodiments, the puller wires are made of any suitable metal, such as stainless steel or Nitinol, and are preferably coated with Teflon® or the like. The coating imparts lubricity to the puller wires. 
         [0057]    A compression coil  36  is situated within the catheter body  12  in surrounding relation to each puller wire  26  and  27 , as shown in  FIG. 3 . The compression coils  36  extend from the proximal end of the catheter body  12  to at or near the proximal end of the deflection section  14 . The compression coils  36  are made of any suitable metal, preferably stainless steel. Each compression coil is tightly wound on itself to provide flexibility, i.e., bending, but to resist compression. The inner diameter of the compression coil is preferably slightly larger than the diameter of the puller wire. A Teflon® coating on each puller wire allows it to slide freely within the compression coil. If desired, particularly if the lead wires  28  and  29  are not enclosed by a protective sheath, the outer surface of the compression coils  36  can be covered by a flexible, non-conductive sheath (not shown), e.g., made of polyimide tubing, to prevent contact between the compression coils  36  and any other wires within the catheter body  12 . 
         [0058]    The puller wire  26  extends through the second lumen  32  of the tubing  19  and the puller wire  27  extends through the fifth lumen  35  of the tubing  19 . Within these lumens, each puller wire extends through a respective plastic, preferably Teflon®, sheath  37  (see  FIG. 4 ), which prevents the puller wires from cutting into the wall of the tubing  19  when the deflection section  14  is deflected. 
         [0059]    Longitudinal movement of the puller wires  26  and  27  relative to the catheter body  12 , which results in deflection of the tip section  14 , is accomplished by suitable manipulation of the control handle  16 . A suitable control handle design for use with the present invention is described in U.S. Pat. No. 8,287,532, the entire disclosure of which is incorporated herein by reference. If desired, the catheter can be uni-deflectional, i.e., having only one puller wire. 
         [0060]    As shown in detail in  FIG. 5A , distal of the deflection section  14  is the inflatable cryoablation assembly  13  including the balloon member  24  which can serve as a substrate on which one or more micro-Peltier modules  15  are provided. The balloon member  24  has a membrane  40  which is flexible and if appropriate or desired, also elastic. 
         [0061]    Fixedly attached to an outer surface of the balloon membrane  40  are one or more micro-Peltier cooling (“MPC”) modules  15 . As shown in  FIG. 5A , each of MPC modules  15   a - 15   i  includes one or more MPC units  50   a - 50   n . As shown in  FIG. 6 , each unit  50   i  has an N-type semiconductor N and a P-type semiconductor P that are configured thermally in parallel to each other by thermally-conducting layers or surfaces  41  and  42 , and electrically in series at junctions X and Y defined by, respectively, first and second electrically-conducting members  51  and  52  at their opposing ends. 
         [0062]    When a voltage is applied to the N-type and the P-type semiconductors of any unit  50   i  via the first and second electrically-conducting members  51  and  52  forming a circuit with a current/voltage source  60 , a DC current flows across junctions X and Y of the N-type and P-type semiconductors (as shown by arrows A) causing a temperature difference between the junctions X and Y of the unit  50   i . With the current/voltage source  60  and the circuit configured such that the current flows first into the N-type semiconductor and then out of the P-type semiconductor, the junction Y is the “hot” junction with the first surface  41  being the “hot” (or relatively hotter) side, and the junction X with the second surface  42  being the “cold” (or relatively colder) side, wherein the “cold/colder” side absorbs heat which is then moved to the other side of the unit  50   i  where the “hot/hotter” side is. Where the MPC unit  50  is configured such that the cold side  42  faces outwardly on the balloon membrane  40  of the balloon member  24 , the cold side functions as cryoablation surface of the inflatable assembly  13  adapted for tissue contact. With the hot side  41  facing inwardly, it is in closer proximity to the balloon membrane  40  and hence adapted for thermal conduction (directly or indirectly) with a heat sink that includes heat-absorbing fluid entering and exiting the interior cavity  25  of the balloon member  24  via feeder fluid tubing  38  and return fluid tubing  39 . Voltage/current source  60  of the Peltier circuit can be adjusted to create a temperature difference between the junctions X and Y ranging between about 50 degrees Celsius, preferably about 60 degrees Celsius, and, more preferably about 70 degrees Celsius. The fluid can be any suitable fluid, including, for example, water or saline. In some embodiments, the MPC circuit can be adjusted such that the hot side  41  is at body temperature, namely, about 37 Celsius, therefore achieving about −33 Celsius on the cold side  42 . With chilled water or saline at about 0 C being the temperature of the hot side  41 , the cold side  42  can be about −70 C which is a temperature well suited for cryoablation. 
         [0063]    As shown in  FIG. 5A  and  FIG. 6 , one or more MPC units  50   a - 50   n  are cascaded together for form an MPC module  15  for lower temperature, with the N-type semiconductor of a first MPC unit  50   a  being connected to one hot wire  28  and the P-type semiconductor of a last MPC unit  50   n  being connected to a neutral wire  29  for forming one Peltier cooling circuit driven by the voltage/current source  60  with a current direction as shown by arrow A. As shown in  FIG. 6 , adjacent MPC units  50   i  and  50 ( i +1) of a MPC module  15  share a common “hot” junction Y such that the units  50   a - 50   n  are joined with current flowing from the P-type semiconductor of a downstream MPC unit  50   i  to the N-type semiconductor of an upstream MPC unit  50 ( i +1). 
         [0064]    With a plurality of n MPC units  50  and a plurality of m MPC modules  15 , a matrix of “n×m” MPC units  50  may be provided on any tissue contacting surface of a catheter, as shown in  FIG. 7 . The MPC modules  15   a - 15   m  can be connected in parallel, all driven by a single voltage/current source  60  via a pair of lead wires  28  and  29 . In other embodiments, each MPC module  15   i  of MPC modules  15   a - 15   m  may have its respective voltage/current source  60   i , and lead wires  28   i  and  29   i , as shown in  FIG. 8 . It is understood that a catheter may have any one or more combinations of MPC modules sharing a voltage/current source, as desired or appropriate. 
         [0065]    The assembly  13  includes one or more feeder and return lead wires  28  and  29 . They may extend along the outer surface of the balloon membrane  40 , affixed thereto, to reach the first and last MPC units  50   a  and  50   n  of each MPC module  15   i , as shown in  FIG. 5A . As described hereinabove, the lead wires  28  and  29  extend through the central lumen  18  of the catheter shaft  12  and the first lumen  31  of the tubing  19  of the deflection  14  before emerging through apertures (not shown) formed in, for example, the wall of a distal section of the tubing  19 . In an alternate embodiment, the lead wires  28  and  29  may extend into the interior cavity  25  of the balloon member  13  and emerge through fluid-tight apertures (not shown) formed in the balloon membrane  40 . 
         [0066]    In other embodiments as shown in  FIG. 9 ,  FIG. 10  and  FIG. 11 , a focal catheter  100  has a distal tip section  113  having one or more end and/or side surfaces  110  adapted for tissue contact. Provided on the surfaces  110  are one or more MPC units  50  forming one or more one or more MPC modules  15 . The one or more units  50  and modules  15  may be arranged in any suitable pattern, including, for example, linear, nonlinear, circular, concentric, nonconcentric patterns and combinations thereof.  FIG. 9  illustrates an embodiment of a parallel linear pattern on a distal end surface of the catheter.  FIG. 10  illustrates an embodiment of longitudinal radial patterns on distal end and circumferential surfaces of the catheter.  FIG. 11  illustrates an embodiment of a circular spiral pattern on a distal dome surface. While the MPC modules  15  of  FIG. 5A  are arranged in a longitudinal pattern in  FIG. 5A , the MPC modules  15  of  FIG. 5B  are arranged in a latitudinal pattern which is suited for ablating ring lesions in an ostium of a pulmonary vein. 
         [0067]    For a focal catheter  100 , the distal tip section  113  whose outer surface supports the MPC modules may be configured as a shell  122  with a sidewall  123  and an interior cavity  125 , as shown in  FIG. 12 , wherein the cavity  125 , as an internal heat sink, is adapted to contain circulating cooling fluid passing through feeder and return fluid tubings (not shown), as described above. Hot and neutral lead wires  128  and  129  may extend through the interior cavity  125  and apertures  126  formed in the sidewall  123  for connection to a first MPC unit  50   a  and a last MPC unit  50   n , respectively, of an MPC module  15   i . The apertures  126  are sealed and fluid-tight. A thermally and electrically insulating sheath  130  surrounds each wire  128  and  129 . 
         [0068]    It is understood that for any embodiments of the catheter of the present invention, the “hot” side  41  counterpart to the “cold” side  42  may be the surface on which the MPC units and modules are supported. For example, the balloon membrane  40  of the balloon member  24  or the side wall  123  of the distal tip shell  122  (either as the substrate for the MPC units) may be the “hot” side  41 , if they are constructed of a suitable material that is thermally conductive but electrically insulative. 
         [0069]    It is also understood that the first and second members  51  and  52  are constructed of material(s) that are both electrically- and thermally-conductive, whereas the “hot” and “cold” layers  41  and  42  are constructed of material(s) that are thermally-conductive but electrically-insulative, so that there is no intended current path through the MPC units from the fluid contained in the interior cavity  125  or from blood or other conductive tissue or bodily fluids near the MPC units. In that regard, the layers  42  may be coextensive in forming a generally contiguous layer that extends over and across the MPC units and modules, sealing them on the substrate and leaving no surface thereof (or at least no surface of conductive components thereof) exposed to unintended current paths. In some embodiments, the membrane  40  is constructed of a thermoplastic material with a low durometer ranging between about 50A and 55D, and preferably between about 80A and 50D. A suitable material includes Pebax or Pellethane, a medical-grade thermoplastic polyurethane elastomer, with superior resilience, low temperature properties/low thermal conductivity, low electrical conductivity (i.e., insulative dielectric properties), and exceptionally smooth surfaces. Another suitable material is flexible polyimide films. 
         [0070]    Suitable materials for lead wires  28 ,  29 ,  128  and  129  include electrically conductive materials with low resistivity to prevent Joule heating and undesired loss in cooling efficiency, including, for example, copper. 
         [0071]    The N-type and P-type semiconductors may include any thermoelectric material with large Peltier coefficients, including appropriately doped bismuth telluride, silicon-germanium and bismuth-antimony. 
         [0072]    The components of the MPC units may be assembled on and/or affixed to the support surface by any suitable methods, including, for example, electrochemical deposition, MEMS (micro-electro-mechanical systems) techniques including photolithography, masking, etching and the like. 
         [0073]      FIG. 13 ,  FIG. 14A  and  FIG. 14B  illustrate another embodiment of a focal catheter  200  of the present invention. The catheter  200  has a dome distal tip section  213  having an MPC unit  250 , wherein the unit has an N-type wire  228 , a P-type wire  229 , an electrically conductive inner concave layer  252  (defining a distal or first junction X with distal ends of the wires  228  and  229 ), and an electrically-insulative and thermally-conductive outer convex layer  242  sealing the layer  252 . It is understood that the layer  252  is optional and ed by directly cooling the Y junction The dome distal tip section  213  is made of an electrically-insulative material, and the material may also be thermally-insulative. The layers  252  and  242  are embedded in a recess  260 , which may be located, for example, at a distal end of the section  213 . In the illustrated embodiment, distal ends the wires  228  and  229  are electrically connected to the layer  252  and extend through respective passages  271  and  272 , and through respective lumens  281  and  282  in a tubing  219  proximal of shell  213 . The wires  228  and  229  extend through a central lumen of a catheter shaft (not shown) and emerge proximally of the control handle  16  where the proximal or second junction Y of the two wires is thermally coupled to an external heat sink  290 , for example, immersed in a bath. Electrified by a voltage/current source  260 , with current flowing toward the layer  252  via the N-type wire  228 , junction X is configured as the “cold/colder” junction with junction Y configured as the “hot/hotter” junction. With adjustment of the voltage/current, the temperature difference between the junctions X and Y can range between at least about 50 degrees Celsius, preferably at least 60 degrees Celsius, and more preferably about 70 degrees Celsius. Accordingly, where the temperature of the “hot/hotter” junction Y is regulated at about −196 Celsius by the bath  290  containing, for example, liquid nitrogen or liquid carbon dioxide, the temperature of the “cold/colder” junction X can reach about −266 Celsius. Where the bath  290  contains dry ice (with a temperature of about −78.5 Celsius), the temperature of junction X can reach about −148.5 Celsius. 
         [0074]    It is understood that in other embodiments the layers  252  and  242  may be configured as an elongated body extending along the longitudinal axis of the distal tip section  213  to resemble and function as a needle  214  (shown in broken lines in  FIG. 14A ) extending distally from the distal end of the section  213 . 
         [0075]    As shown in  FIG. 14C , another embodiment of a focal catheter  300  is shown with a distal section  313  having an MPC unit  350  and an internal heat sink. The internal heat sink includes an interior cavity  325  that is circulated with a fluid of a predetermined temperature that enters and exits the interior cavity  325  via feeder and return fluid tubings  338  and  339 . 
         [0076]    The MPC unit  350  has an N-type semiconductor N and a P-type semiconductor P that are configured thermally in parallel to each other by thermally-conducting, electrically insulative proximal and distal layers or surfaces  341  and  342 , and electrically in series at cold and hot junctions X and Y defined by, respectively, first and second electrically-conducting members  351  and  352  at their opposing ends. The tissue contact surface of the catheter includes the distal layer or surface  342 . 
         [0077]    Hot lead wire  328  is electrically connected to the N-type semiconductor N and the neutral lead wire  329  is electrically connected to the P-type semiconductor P, such that the first member  351  is the hot side or junction and the second member  352  is the cold side or junction of the MPC unit  350 . The thermally-conducting, electrically insulative layers  341  and  342  prevent any unintended current path through the MPC unit from fluid contained in the interior cavity  325  or from blood or other conductive tissue or bodily fluids near the MPC units. 
         [0078]    The first member  351  or hot side is in closer proximity to the interior cavity  325  as a heat sink such that its temperature is regulated by the fluid contained in the interior cavity  325  via thermal conduction across the layer  341 . Thus, the second member  352  presenting the cold side is in closer proximity to the distal layer  342  which is configured for tissue contact. 
         [0079]    It is understood that the catheter  313  may include any number of MPC units  350  sharing the interior cavity  325  and fluid as their common heat sink, wherein the respective second members  352  of the units  350  are presented as the cold side for tissue contact. 
         [0080]    In yet other embodiments, the layers  252  and  242  may be deposited electrochemically on a flexible polyimide film  280 , as shown in  FIG. 15A , rolled into a cylindrical body  291 , with the layer  252  facing outwardly and the film  280  facing inwardly, as shown in  FIG. 15B , and assembled as component of a tip section  213  extending longitudinally and distally of the tip section  213 , as shown in  FIG. 16 . A distal end of the cylindrical body  291  may be capped and sealed with a sealant  295 , for example, polyurethane or epoxy. 
         [0081]    As part of an MPC circuit, the wires  228  and  229  are constructed of electrical conductors. In some embodiments, one or both of these wires may be constructed of drawn and appropriately-doped bismuth telluride, silicon-germanium and bismuth-antimony, for example, N-doped bismuth telluride for an N-type wire  228  and P-doped bismuth telluride for P-type wire  229 . 
         [0082]    It is understood that the present invention includes embodiments wherein the voltage/current source and the MPC components and/or circuit are configured such that the current direction is in the opposite direction, where the hot side faces outwardly or is the outer contact surface and the cold side faces inwardly or is the inner surface of the distal portion of the catheter, as desired or appropriate. 
         [0083]    The preceding description has been presented with reference to presently disclosed embodiments of the invention. Workers skilled in the art and technology to which this invention pertains will appreciate that alterations and changes in the described structure may be practiced without meaningfully departing from the principal, spirit and scope of this invention. As understood by one of ordinary skill in the art, the drawings are not necessarily to scale and any feature or combinations of features described in any one embodiment may be incorporated into any other embodiments or combined with any other feature(s) of other embodiments, as desired or needed. Accordingly, the foregoing description should not be read as pertaining only to the precise structures described and illustrated in the accompanying drawings, but rather should be read consistent with and as support to the following claims which are to have their fullest and fair scope.