Patent Publication Number: US-2020289199-A1

Title: Electrosurgical instrument for freezing and ablating biological tissue

Description:
FIELD OF THE INVENTION 
     The invention relates to an electrosurgical probe for ablating biological tissue using microwave energy. In particular, the probe can be used in the lungs or in the uterus, for example to ablate tumours, lesions or fibroids and to treat asthma. The probe may be inserted through a working channel of a surgical scoping device or catheter, or may be used in laparoscopic surgery or open surgery. 
     BACKGROUND TO THE INVENTION 
     It is inherently difficult to gain access to lung tumours due to the small dimensions of the bronchial tree, especially towards the peripheral regions where small nodules are likely to develop. This has resulted in many treatment options being employed such as chemotherapy (targeted medicine, anti-cancer drugs (chemotherapeutic agents)), radiotherapy (delivery of ionizing radiation), surgery (invasive and minimally invasive) and RF/microwave ablation. Surgical procedures for the removal of lung tumours include pneumonectomy (removal of one lung), lobectomy (removal of a lobe), sleeve lobectomy (resection of a lobe along with part of the bronchus that attaches to it), wedge resection (removal of a wedge shaped portion of lung) and segmentectomy/segment resection (resection of a specific lung segment). 
     Biological tissue is largely composed of water. Human soft organ tissue is typically between 70% and 80% water content. Water molecules have a permanent electric dipole moment, meaning that a charge imbalance exists across the molecule. This charge imbalance causes the molecules to move in response to the forces generated by application of a time varying electric field as the molecules rotate to align their electric dipole moment with the polarity of the applied field. At microwave frequencies, rapid molecular oscillations result in frictional heating and consequential dissipation of the field energy in the form of heat. This is known as dielectric heating. 
     This principle is harnessed in microwave ablation therapies, where water molecules in target tissue are rapidly heated by application of a localised electromagnetic field at microwave frequencies, resulting in tissue coagulation and cell death. It is known to use microwave emitting probes to treat various conditions in the lungs and other body tissues. For example, in the lungs, microwave radiation can be used to treat asthma and ablate tumours or lesions. 
     Conventional microwave ablation probes are designed to be inserted into the patient percutaneously. However, such probes are difficult to locate percutaneously into a moving lung, which can lead to complications such as pneumothorax and haemothorax (air and blood within the pleural cavity respectively). Other microwave ablation probes can be delivered to a target site by a surgical scoping device (e.g. a bronchoscope or other type of endoscope) which can be run through channels in the body such as airways. This allows for minimally invasive treatments, which can reduce the mortality rate of patients and reduce intraoperative and postoperative complication rates. 
     Using a probe to deliver the microwave energy to target tissue is desirable because the radiating portion can be positioned close to the target site, such that a high proportion of power can be transmitted to the target site and a lower proportion is lost to the surrounding healthy tissue. This reduces side effects of treatment as well as increasing efficiency. 
     Because microwave energy rapidly dissipates in biological tissues, biological tissues are often described as lossy materials. Microwave energy radiated from an ablation probe therefore does not propagate far in biological tissue before it is completely dissipated. The volume over which microwave energy is dissipated in biological tissue is frequency dependent and can be described using a quantity called skin depth. Skin depth is defined as the distance away from the surface a radiating antenna of the ablation probe at which microwave power has been reduced by a factor of 1/e compared to the total power radiated by the antenna (where e is the number whose natural logarithm is equal to one). 
     By way of example,  FIG. 5  shows a graph of skin depth versus frequency over a frequency range of 0.5-10 GHz, which covers a typical range of microwave ablation frequencies. The skin depth was calculated for in-vivo liver, using measured complex permittivity data. As shown in  FIG. 5 , at an example ablation frequency of 5.8 GHz the skin depth is around 8 mm. This means that most of the microwave energy is dissipated less than 1 cm away from the surface of the radiating antenna. The size of a treatment area for microwave ablation probes is therefore limited to a small region around the radiating antenna. 
     The size of the treatment area can be increased by increasing the amount of microwave energy delivered to the radiating antenna, i.e. the power transferred to the antenna. However, the cable that conveys the energy to the antenna is itself lossy, and typically the rate of loss increases as the diameter of the cable decreases. This effectively limits the amount of energy which can be delivered, in order to avoid collateral damage caused by cable heating. Increasing the amount of microwave energy can also cause the probe to generate large amounts of heat, such that it is necessary to use a cooling mechanism to avoid damage to the probe and/or patient. 
     SUMMARY OF THE INVENTION 
     At its most general, the present invention provides an electrosurgical apparatus for applying microwave energy to biological tissue, where the apparatus is capable of freezing biological tissue in a region around a radiating tip portion of the apparatus and applying microwave energy to the frozen tissue. As water molecules in frozen tissue have reduced vibrational and rotational degrees of freedom compared to non-frozen tissue, less energy is lost to dielectric heating when microwave energy is transmitted through frozen tissue. Thus, by freezing the region around the radiating tip portion, microwave energy radiated from the radiating tip portion can be transmitted through the frozen region with low losses and into tissue surrounding the frozen region. This enables the size of the treatment area to be increased compared with conventional microwave ablation probes, without having to increase the amount of microwave energy delivered to the radiating tip portion. Once the tissue surrounding the frozen region has been ablated with microwave energy, the frozen region can be allowed to progressively thaw so that it will dissipate microwave energy and be ablated. The apparatus of the invention also enables various combinations of microwave energy and tissue freezing to be used to effectively ablate biological tissue. The electrosurgical device can be configured to be fed through the working channel of an endoscope, so that it can be used to carry out minimally invasive surgical procedures. 
     According to a first aspect of the invention, there is provided an electrosurgical instrument for treating biological tissue, the instrument comprising: a transmission line for conveying microwave electromagnetic (EM) energy; a radiating tip mounted at a distal end of the transmission line to receive and radiate the microwave EM energy from the transmission line into a treatment zone around the radiating tip; a fluid feed for conveying a tissue-freezing fluid to the treatment zone; and a thermal transfer portion connected to receive the tissue-freezing fluid from the fluid feed at a distal end of the transmission line, wherein the thermal transfer portion is arranged to provide thermal communication between the tissue-freezing fluid and biological tissue in the treatment zone to freeze the biological tissue in the treatment zone. 
     The radiating tip may comprise a microwave antenna. The antenna may be a conventional monopole antenna formed on the end of the transmission line. The transmission line may be a coaxial transmission line, e.g. a conventional coaxial cable. An inner conductor of the coaxial cable may be connected to a radiating tip of the microwave antenna from which microwave energy can radiate. The radiating tip may include one or more dielectric materials to provide dielectric loading of the antenna, in order to enhance or shape the energy emission profile of the microwave antenna. The coaxial feed cable includes an outer conductor which is separated from the inner conductor by a dielectric material. 
     The electrosurgical instrument can be used to apply microwave energy to matter in its vicinity, such as biological tissue, fluids or other materials. Microwave energy can cause dielectric heating in biological tissue, which can be used to ablate tissue in a localised volume around the antenna. Therefore, by inserting the antenna directly into a treatment zone, including e.g. a tumour, lesion or fibroid, microwave energy can be applied to tissue in the treatment zone in order to ablate it. 
     The electrosurgical instrument enables biological tissue in the treatment zone located around the radiating tip to be frozen. Herein, biological tissue is said to be “frozen” if the water contained in the biological tissue is in ice form, i.e. water molecules in the biological tissue are held in a crystal structure. Tissue is said to be “non-frozen” if the water molecules in the tissue are in a liquid state. Frozen tissue has a lower dielectric loss factor at microwave frequencies compared to non-frozen tissue, thus enabling it to transmit microwave energy more efficiently than non-frozen tissue. The dielectric loss factor is related to the imaginary part of a material&#39;s permittivity, and is indicative of energy dissipation in the material. 
     The tissue-freezing fluid may be a cryogenic liquid or gas, and may be referred to herein as a cryogen. The term “cryogen” may refers to a substance which is used to produce temperatures below 0° C. Liquid, gas or solid cryogens may be used. Suitable cryogens include, but are not limited to liquid nitrogen, liquid carbon dioxide and liquid nitrous oxide. The fluid feed may be provided with a thermal insulation layer made of a thermally insulating material and/or a vacuum jacket to prevent other parts of the apparatus from being cooled by the cryogen. This can also ensure that only tissue in the treatment zone is frozen, and that other parts of the patient which may be in close proximity to the cryogen conveying conduit are not affected by the cryogen. 
     The flow of tissue-freezing fluid through the fluid feed may be adjusted to control the cooling power of the electrosurgical instrument. For example. the flow of tissue-freezing fluid may be increased to increase the cooling power, thereby causing tissue in the treatment zone to freeze. The flow of tissue-freezing fluid may be reduced or stopped to allow tissue in the treatment zone to thaw. The cooling power may determine the volume of tissue which is frozen (e.g. the greater the cooling power, the larger the volume of tissue which is frozen). Herein the term “cooling power” is used to describe the instrument&#39;s ability to remove heat from an area. 
     The thermal transfer portion may be arranged so that it is cooled by the tissue-freezing fluid delivered by the fluid feed and so that it may come in direct contact with the biological tissue in the treatment zone. In this manner, the thermal transfer portion can be brought into contact with tissue which is to be frozen. The tissue-freezing fluid can then cool the thermal transfer portion, which in turn freezes the tissue. The thermal transfer portion may be made of a thermally conductive material such as a metal or other suitable material. The thermal transfer portion may have a first portion which is configured to come into contact with the tissue-freezing fluid from the fluid feed and a second portion which is configured to come into contact with biological tissue. A heater may be mounted on or near the thermal transfer portion in order to enable more accurate temperature control of the thermal transfer portion. 
     The fluid feed may be arranged to circulate the tissue-freezing fluid through the thermal transfer portion. For example, the fluid feed may comprise a delivery conduit for conveying the tissue-freezing fluid to the thermal transfer portion, and an exhaust conduit for conveying the tissue-freezing fluid away from the thermal transfer portion. This prevents build-up of pressure in the cryogenic instrument. The term “used cryogen” refers to cryogen which has come into contact with the first portion of the tissue-freezing element, and thereby absorbed heat from the tissue-freezing element. 
     The thermal transfer portion may comprise a enclosed reservoir for receiving the tissue-freezing fluid, e.g. in the first portion thereof. An inlet of the reservoir may be connected to an outlet of the delivery conduit, and an outlet of the reservoir may be connected to an inlet of the exhaust conduit. The instrument may comprise a pump for causing the tissue-freezing fluid flow through the instrument. 
     The second portion of the thermal transfer portion may include a protective outer layer made of a biologically inert material. 
     In some examples, the instrument circulates the tissue-freezing fluid in a closed circuit. In other examples, the thermal transfer portion may include an outlet for delivering the tissue-freezing fluid into the treatment zone. The outlet may include a nozzle arranged to spray the tissue-freezing fluid into the treatment zone. In such an example, the instrument may further include a decompression tube through which gas in the treatment zone may escape. This avoids build-up of pressure in the treatment zone, which could cause internal damage to the patient. This is particularly important where a liquid cryogen is used, as the liquid cryogen will rapidly expand into a gas when it comes into contact with warm tissue. 
     The decompression tube may have a gas inlet located near the distal end of instrument, through which gas in the treatment zone may enter, and an exhaust outlet located near a proximal end of the instrument through which the gas may exit. The gas inlet and/or exhaust outlet may be fitted with one way valves to prevent gas entering into the treatment zone through the decompression tube. The gas inlet and/or exhaust outlet may be fitted with a pressure relief valve configured to automatically open when pressure in the treatment zone reaches a predetermined threshold, to ensure that pressure in the treatment zone is kept at a safe level. The instrument may also include a pressure sensor located near its distal end for monitoring pressure in the treatment zone. 
     The thermal transfer portion may have other configurations. For example, the thermal transfer portion may include a balloon which is fluidly connected to the fluid feed so that it can be inflated with the tissue-freezing fluid. 
     The thermal transfer portion may include a tissue-freezing element that is movable between an exposed position where it protrudes distally beyond the radiating tip, and a retracted position in which it is set back from the radiating tip. The tissue-freezing element may be moved between the two positions using one or more control wires. This enables the tissue-freezing element to be deployed only when the user wishes to make use of the freezing functionality, so that the tissue-freezing element does not cause any accidental injuries when not in use. The distal end of the electrosurgical instrument may also include a sheath or protective hull which covers the tissue-freezing element when it is in the retracted position, to further improve safety. 
     The transmission line and the fluid feed may be within a common cable. In some examples, the fluid feed is integrated with the transmission line. For example, the transmission line may be a coaxial transmission line comprising an inner conductor, an outer conductor, and a dielectric material separating the inner conductor and the outer conductor, and wherein the inner conductor is hollow to provide a passageway for the fluid feed. The tissue-freezing element may be slidably mounted in the passageway. An inner wall of the hollow inner conductor may form part of the cryogen delivery conduit. The cryogen may therefore also serve to cool the coaxial feed cable. 
     The integration of the two functionalities can provide a compact device and simplify ablation procedures, as it does not require different components to be inserted or removed from the working channel of an endoscope during an ablation procedure. 
     The instrument may include a temperature sensor mounted at a distal end of the transmission line to detect a temperature of the treatment zone. Control of the tissue-freezing fluid flow and microwave energy delivery may be based on a detected temperature. 
     The instrument may be used in an electrosurgical apparatus for treating biological tissue, the apparatus also comprising an electrosurgical generator arranged to supply microwave electromagnetic (EM) energy, and a tissue-freezing fluid supply. The electrosurgical instrument may be connected to receive the microwave EM energy from the electrosurgical generator and to receive the tissue-freezing fluid from the tissue-freezing fluid supply. The apparatus may further comprise a controller configured to: cause the tissue-freezing fluid to flow through the fluid feed to the thermal transfer portion to freeze biological tissue in the treatment zone; detect conditions in the treatment zone to determine if biological tissue in the treatment zone is frozen; and in response to determining that biological tissue in the treatment zone is frozen, cause the microwave energy to be delivered from the radiating tip. The controller may also be configured to, in response to determining that biological tissue in the treatment zone is frozen, reduce or stop the flow of tissue-freezing fluid through the fluid feed. The controller may be configured to determine whether the biological tissue in the treatment zone is frozen based on any one or more of: a detected impedance of the treatment zone, and a detected temperature of the treatment zone. 
     The controller may be a conventional computing device which is operatively connected to the instrument to control the flow of tissue-freezing fluid. For example the controller may control one or more valves and/or a pump which can be used to regulate the flow of cryogen through the delivery conduit. Reducing or stopping the flow of cryogen when the controller determines that the biological tissue in the treatment zone is frozen avoids the risk of freezing tissue outside of a desired target area, which could cause damage to surrounding healthy tissue. 
     Conversely, if the controller determines that the biological tissue in the treatment zone is not frozen, or that it is thawing, the controller may increase the flow of cryogen through the delivery conduit in order to freeze the tissue in the treatment zone. The controller may also be configured to regularly monitor the state (e.g. frozen or non-frozen) of tissue in the treatment zone and adjust the flow of cryogen through the cryogen conveying conduit so that the tissue in the treatment zone reaches a desired state (e.g. frozen or non-frozen). The controller therefore provides an automated mechanism for controlling the freezing of tissue in the treatment zone, and reduces the risk of damaging tissue outside the treatment zone. 
     In some embodiments, the controller may be configured to, in response to determining that the biological tissue in the treatment zone is frozen, cause the electrosurgical instrument to deliver microwave energy to the biological tissue in the treatment zone. The controller may be configured to control the generator which is connected to provide the microwave energy to the electrosurgical instrument. In some examples, the controller may be integrated with the generator. As the biological tissue in the treatment zone is frozen when the microwave energy is delivered, the microwave energy may be transmitted with low losses by the frozen tissue to surrounding non-frozen tissue which can be ablated by the microwave energy. This can increase the effective volume of tissue treated. 
     The controller may use several methods to determine whether the biological tissue in the treatment zone is frozen. In some embodiments, the electrosurgical apparatus may further include a sensor disposed near the radiating tip portion, and the controller may be configured to determine whether the biological tissue in the treatment zone is frozen based on a measurement obtained from the sensor. The sensor may be any suitable sensor for measuring a property of biological tissue, where the property varies according the tissue&#39;s state (i.e. frozen or non-frozen). For example, the sensor may be a temperature sensor arranged to measure the temperature of biological tissue in the treatment zone. The sensor may be a pressure sensor arranged to detect a change in pressure when the tissue freezes (e.g. because of the expansion of water when it freezes). 
     In other examples, the controller may be configured to determine whether the biological tissue in the treatment zone is frozen based on an impedance measurement of the biological tissue in the treatment zone. An impedance measurement may be carried out for example by delivering a pulse of microwave energy to the radiating tip portion, and measuring microwave energy which is reflected back up the coaxial feed cable. Microwave energy may be reflected back at the radiating tip portion due to an impedance mismatch between the radiating tip portion and the biological tissue in the treatment zone. The impedance of biological tissue is a function of the permittivity and the conductivity of the biological tissue at a frequency of interest, and hence depends on whether the biological tissue is frozen or non-frozen. By measuring the reflected microwave energy, the impedance of the biological tissue in the treatment zone can be estimated in order to determine whether the biological tissue is frozen or not. A low power microwave pulse can be used to measure the impedance of the biological tissue, so that the measurement does not cause any tissue ablation. 
     Optionally, the electrosurgical apparatus may also include a separate fluid delivery mechanism for transporting fluid to and from the treatment zone. The fluid delivery mechanism may be used to inject a fluid into the treatment zone and/or aspirate fluid from the treatment zone. The fluid delivery mechanism may include a flexible fluid conveying conduit that extends along the coaxial cable, and a rigid insertion element in communication with a distal end of the fluid conveying conduit and arranged to extend into the treatment zone. For example the rigid insertion element may be a hollow needle which can be exposed using one or more control wires in order to pierce tissue in the treatment zone. The fluid delivery mechanism may also be used to aspirate tissue samples from the treatment zone in order to perform a biopsy. 
     The electrosurgical apparatus discussed above may form part of a complete electrosurgical system. For example, the apparatus may include a surgical scoping device having an flexible insertion cord for non-percutaneous insertion into a patient&#39;s body, wherein the flexible insertion cord has an instrument channel running along its length, and wherein the electrosurgical instrument is dimensioned to fit within the instrument channel. 
     It should be noted that the microwave ablation and tissue-freezing functionalities of the instrument may be used independently. For example, microwave energy may be applied directly to tissue without cooling or freezing the tissue, in order to ablate the tissue. Tissue may also be ablated by repeatedly freezing and thawing a volume of tissue, without having to apply microwave energy to it. The electrosurgical apparatus of the invention therefore provides a flexible tissue ablation tool, as it enables different ablation techniques to be combined depending on the requirements of a particular situation. 
     Also disclosed herein is a method for treating biological tissue, the method comprising: non-percutaneously inserting an instrument cord of a surgical scoping device into a patient, the surgical scoping device having an instrument channel running along its length; conveying an electrosurgical instrument as described above along the instrument channel to a treatment zone at a distal end thereof; flowing a tissue-freezing fluid through the fluid feed to freeze biological tissue in the treatment zone; and after biological tissue is frozen in the treatment zone, delivering microwave energy to the radiating tip portion. Any feature of the electrosurgical apparatus and system discussed herein may be utilised in the method. For example, the method may include detecting a temperature in the treatment zone, and controlling delivery of the microwave energy based on the detected temperature. Alternatively or additionally, the method may include detecting an impedance in the treatment zone, and controlling delivery of the microwave energy based on the detected impedance. 
     Herein, the terms “proximal” and “distal” refer to the ends of a structure (e.g. electrosurgical instrument, coaxial feed cable, etc.) further from and closer to the treatment zone respectively. Thus, in use the proximal end of the structure is accessible by a user, whereas the distal end is closer to the treatment site, i.e. the patient. 
     The term “conductive” is used herein to mean electrically conductive, unless the context dictates otherwise. 
     The term “longitudinal” used below refers to the direction along the instrument channel parallel to the axis of the coaxial transmission line. The term “lateral” refers to a direction that is perpendicular to the longitudinal direction. The term “inner” means radially closer to the centre (e.g. axis) of the instrument channel. The term “outer” means radially further from the centre (axis) of the instrument channel. 
     The term “electrosurgical” is used in relation an instrument, apparatus or tool which is used during surgery and which utilises microwave electromagnetic (EM) energy. Herein, “microwave EM energy” may mean electromagnetic energy having a stable fixed frequency in the range 300 MHz to 100 GHz, preferably in the range 1 GHz to 60 GHz. Preferred spot frequencies for the microwave EM energy include 915 MHz, 2.45 GHz, 5.8 GHz, 14.5 GHz, 24 GHz. 5.8 GHz may be preferred. 
     In use, the treatment zone may include biological tissue in a patient&#39;s lungs, uterus, gastrointestinal tract or other organs. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Examples of the invention are discussed below with reference to the accompanying drawings, in which: 
         FIG. 1  is a schematic diagram of an electrosurgical apparatus for tissue ablation that is an embodiment of the invention; 
         FIG. 2  is a schematic cross-sectional view of a distal end of an ablation instrument suitable for use in the invention; 
         FIG. 3  is a schematic cross-sectional view of a distal end of another ablation instrument suitable for use in the invention; 
         FIG. 4A  is a schematic illustration of a tissue ablation method that is an embodiment of the invention; 
         FIG. 4B  is a schematic illustration of another tissue ablation method that is an embodiment of the invention; and 
         FIG. 5  is a graph of calculated skin effect versus frequency over a range of microwave frequencies used for tissue ablation. 
     
    
    
     DETAILED DESCRIPTION; FURTHER OPTIONS AND PREFERENCES 
       FIG. 1  is a schematic diagram of a complete electrosurgical apparatus  100  that is an embodiment of the invention. The apparatus  100  is arranged to treat biological tissue (e.g. a tumour, lesion or fibroid) using microwave energy delivered from a microwave antenna. The apparatus  100  is capable of freezing a volume of biological tissue, and ablating tissue surrounding the frozen tissue by applying microwave energy to the frozen tissue. Applying microwave energy to frozen tissue enables microwave energy to be transmitted further into a sample of tissue, as frozen tissue does not dissipate microwave energy as strongly as non-frozen tissue. This enables the total volume of tissue which can be treated by the applied microwave energy to be increased, without having to increase the amount of microwave energy delivered. 
     The system  100  comprises a generator  102  for controllably supplying microwave energy. A suitable generator for this purpose is described in WO 2012/076844, which is incorporated herein by reference. The generator may be arranged to monitor reflected signals received back from the instrument in order to determine an appropriate power level for delivery. For example, the generator may be arranged to calculate an impedance seen at the distal end of the instrument in order to determine an optimal delivery power level. 
     The generator  102  is connected to an interface joint  106  by an interface cable  104 . The interface joint  106  is also connected to a cryogen supply unit  108 , such as a cryogen-carrying vessel, via a cryogen conveying conduit  107 . If needed, the interface joint  106  can house an instrument control mechanism that is operable by sliding a trigger  110 , e.g. to control longitudinal (i.e. back and forth) movement of one or more control wires or push rods (not shown). If there is a plurality of control wires, there may be multiple sliding triggers on the interface joint to provide full control. An exhaust conveying conduit  120  may also be connected to the interface joint  106 , through which used cryogen and/or exhaust gas may exit. The function of the interface joint  106  is to combine the inputs from the generator  102 , cryogen supply unit  108 , the exhaust conveying conduit  120  and instrument control mechanism into a single flexible shaft  112 , which extends from the distal end of the interface joint  106 . 
     The flexible shaft  112  is insertable through the entire length of a working (instrument) channel of a surgical scoping device  114 , such as a bronchoscope, endoscope, gastroscope, laparoscope or the like. The flexible shaft  112  has a distal assembly  118  (not drawn to scale in  FIG. 1 ) that is shaped to pass through the working channel of the surgical scoping device  114  and protrude (e.g. inside the patient) at the distal end of the surgical scoping device&#39;s working channel. The distal end assembly  118  includes a microwave antenna for delivering microwave energy and a tissue-freezing element (not shown) connected to the cryogen conveying conduit  107  for freezing tissue. The tip configuration is discussed in more detail below. 
     Cryogen may be delivered to the tissue-freezing element from the cryogen supply unit  108  via the cryogen conveying conduit  107 . In certain embodiments, the cryogen is used to cool the tissue-freezing element (e.g. via heat exchange processes). In this case, the cryogen may flow into the tissue-freezing element via the cryogen conveying conduit  107 , and back out of the tissue-freezing element via the exhaust conveying conduit  120 . In other embodiments, the tissue-freezing element includes a nozzle which is used to spray cryogen onto a target area. The cryogen may then escape from the target area via the exhaust conveying conduit  120 , to avoid build-up of pressure in the target area. The proximal end of the exhaust conveying conduit  120  may be open to the atmosphere, or it may be connected to a collection chamber (not shown) where used cryogen may be collected. Different cryogen supply units may be connected to the cryogen conveying conduit  107  depending on the cryogen to be used. 
     The structure of the distal assembly  118  may be arranged to have a maximum outer diameter suitable for passing through the working channel. Typically, the diameter of a working channel in a surgical scoping device such as an endoscope is less than 4.0 mm, e.g. any one of 2.8 mm, 3.2 mm, 3.7 mm, 3.8 mm. The length of the flexible shaft  112  can be equal to or greater than 1.2 m, e.g. 2 m or more. In other examples, the distal assembly  118  may be mounted at the distal end of the flexible shaft  112  after the shaft has been inserted through the working channel (and before the instrument cord is introduced into the patient). Alternatively, the flexible shaft  112  can be inserted into the working channel from the distal end before making its proximal connections. In these arrangements, the distal end assembly  118  can be permitted to have dimensions greater than the working channel of the surgical scoping device  114 . 
     The apparatus described above is one way of introducing the device. Other techniques are possible. For example, the device may also be inserted using a catheter. 
     The invention seeks to provide a device that can ablate biological tissue by applying microwave energy directly to the tissue, and/or by freezing a volume of tissue and applying microwave energy to the frozen tissue. The device is particularly suited to the ablation of tissue in the lungs or uterus, however it may be used to ablate tissue in other organs. In order to efficiently ablate target tissue, the microwave antenna and tissue-freezing element should be located as close as possible (and in many cases inside) the target tissue. In order to reach the target tissue (e.g. in the lungs), the device will need to be guided through passageways (e.g. airways) and around obstacles. This means that the instrument will ideally be flexible and have a small cross section. Particularly, the device should be very flexible near its tip, where it may need to be steered along passageways such as bronchioles which can be narrow and winding. 
     It is also preferable that the device can be operated alongside other instruments to enable practitioners to receive information from the target site. For example, an endoscope may aid the steering of the instruments around obstacles and to a desired position. Other instruments may include a thermometer or camera. 
       FIG. 2  is a schematic cross-sectional view of a distal end of an electrosurgical device  200  that is an embodiment of the invention. The electrosurgical device  200  includes an electrosurgical instrument  201  and a cryogenic instrument  202 . 
     Electrosurgical instrument  201  includes a coaxial feed cable  204  that is connected at its proximal end to a generator (such as generator  102 ) in order to convey microwave energy. The coaxial feed cable  204  comprises an inner conductor  206 , which is separated from an outer conductor  208  by a first dielectric material  210 . The coaxial feed cable  204  is preferably low loss for microwave energy. A choke (not shown) may be provided on the coaxial feed cable  204  to inhibit back propagation of microwave energy reflected from the distal end and therefore limit backward heating along the device. 
     The coaxial feed cable  204  terminates at its distal end with a radiating tip portion  205  for radiating microwave energy. In this embodiment, the radiating tip portion  205  comprises a distal conductive section  212  of the inner conductor  206  that extends before a distal end  209  of the outer conductor  208 . The distal conductive section  212  is surrounded at its distal end by a dielectric tip  214  formed from a second dielectric material, which is different from the first dielectric material  210 . The length of the dielectric tip  214  is shorter than the length of the distal conductive section  212 . An intermediate dielectric sleeve  216  surrounds the distal conductive section  212  between the distal end of the coaxial cable  202  and the proximal end of the dielectric tip  214 . The intermediate dielectric sleeve  216  is formed from a third dielectric material, which is different from the second dielectric material but which may be the same as the first dielectric material  210 . The dielectric tip  214  may have any suitable distal shape. In  FIG. 2  it has a dome shape, but this is not necessarily essential. For example, it may be cylindrical, conical, etc. However, a smooth dome shape may be preferred because it increases the mobility of the antenna as it is manoeuvred through small channels. The electrosurgical instrument  201  is housed in a protective sheath  218  which electrically insulates the electrosurgical instrument  201 . The protective sheath  218  may be made of, or coated with, a non-stick material such as PTFE to prevent tissue from sticking to the instrument. 
     The properties of the intermediate dielectric sleeve  216  are preferably chosen (e.g. through simulation or the like) so that the radiating tip portion  205  forms a quarter wave impedance transformer for matching the input impedance of the generator into a biological tissue load in contact with the radiating tip portion  205 . This configuration of the radiating tip portion  205  may produce an approximately spherical radiation pattern about the radiating tip portion  205 . This enables the user to accurately radiate target tissue and reduces radiation of or damage to healthy tissue. Depending on the radiation pattern required, different radiating tip portion configurations may be used. For example, an asymmetric radiation pattern can be produced by extending the outer conductor  208  along one side of the radiating tip portion  205 . 
     The cryogenic instrument  202  includes a tissue-freezing element  220  at a distal end of the cryogenic instrument  202 , located near the radiating tip portion  205 . The tissue-freezing element  220  includes a reservoir  222  for receiving cryogen delivered by a cryogen conveying conduit  224 . The tissue-freezing element  220  also includes a tip portion  226  which is thermally linked to the reservoir  222  so that the tip portion  226  may be cooled by cryogen in the reservoir  222 . The tissue-freezing element  220  may for example be formed of a single piece of thermally conductive material, with the reservoir  222  being formed by a cavity in the material. 
     The cryogenic instrument  202  also includes an exhaust conveying conduit  228  connected to the reservoir  222  for conveying cryogen from the reservoir  222  to a proximal end of the apparatus where the cryogen may be collected or disposed of. Thus, as indicated by flow direction arrows  230 , cryogen may be conveyed through the cryogen conveying conduit  224  so that it is delivered into the reservoir  222 . The cryogen can accumulate in the reservoir  222 , causing the tip portion  226  of the tissue-freezing element  220  to cool down, so that it may be used to freeze tissue. Excess cryogen in the reservoir  222  may be evacuated through the exhaust conveying tube  228  as indicated by arrows  232 , to avoid a build-up of pressure in the reservoir  222 . In the case of a liquid cryogen (e.g. liquid nitrogen), the cryogen may expand into a gas as it absorbs heat from the tip portion. The gas may also form part of the cryogen which is evacuated through the exhaust conveying conduit  228 . Both the cryogen conveying conduit  224  and the exhaust conveying conduit  228  may be fitted with one way valves to ensure that cryogen flows only in the direction indicated by arrows  230  and  232 . A pump located at the proximal end of the electrosurgical device may be used to circulate cryogen in the cryogen conveying conduit  224  and the exhaust conveying conduit  228 . 
     A thermally insulating sleeve  234  surrounds the cryogen conveying conduit  224 , the exhaust conveying conduit  228  and part of the tissue-freezing element  220 . The thermally insulating sleeve  234  prevents heat from being exchanged between cryogen in the conduits and the surrounding environment. Additionally or alternatively, the cryogen conveying conduit  224  and the exhaust conveying conduit  228  may themselves be made of a thermally insulating material. Thermal insulation of the conduits may be improved by creating a vacuum in the space inside the thermally insulating sleeve  234 . Thermal insulation of the conduits ensures that only tissue in the vicinity of the tissue-freezing element  220  may be frozen, thus avoiding accidental cold damage to the patient. 
     The tissue-freezing element  220  may be slidable within the thermally insulating sleeve  234  along its length. The fit between the outer surface of the tissue-freezing element  220  and the inner surface of the thermally insulating sleeve may be sufficiently tight so that it forms an air-tight sliding seal. The reservoir  222  may be slidably connected to conduits  224  and  228  (e.g. via sliding seals) to enable the tissue-freezing element  220  to move relative to the conduits  224  and  228 . Alternatively, the connections between the reservoir  222  and the conduits  222  and  228  may be fixed, such that the conduits  224  and  228  move with the tissue-freezing element in the thermally insulating sleeve  234 . The tissue-freezing element  220  can be slid along the thermally insulating sleeve  234  using a control wire  236  which passes through the thermally insulating sleeve  234  and is connected at one end to the tissue-freezing element  220 . The tissue-freezing element may be fully or partially retracted into the thermally insulating sleeve  234 , so that its tip portion  226  does not protrude beyond the distal end of the electrosurgical instrument  201 . When a user wishes to use the tissue-freezing element  220  to freeze biological tissue, the tissue-freezing element  220  may be exposed such that it protrudes beyond the distal end of the electrosurgical instrument  201 , so that it may come into contact with target tissue. The tissue-freezing element  220  may be placed in its retracted position when the instrument is being navigated to a target area, to avoid the tip portion  226  catching on tissue or causing accidental injury. Alternative mechanisms to that described above are possible for enabling the tissue-freezing element  220  to move relative to the electrosurgical instrument  201 . 
     A heater and temperature sensor (not shown) may be mounted near the tip portion  226  of the tissue-freezing element  220  to enable accurate control of the temperature at the tip portion  226 . The heater may be a resistive chip which heats up when an electrical current is passed through it. By balancing heat generated by the heater with the cooling power provided by the cryogen, a stable temperature can be obtained at the tip portion  226 . A PID controller may be used to control the temperature to the tip portion  226 . The heater may also be used to heat the tip portion  226  in order to thaw frozen tissue. 
     The cryogenic instrument  202  may be fixed relative to the electrosurgical instrument  201 , so that the two components form a single integrated device which is configured to fit in the working channel of an endoscope. For example, the thermally insulating sleeve  234  may be secured to the protective sheath  218  of the electrosurgical instrument  201 . 
     The tip portion  226  of the tissue-freezing element  220  shown in  FIG. 2  is dome shaped. However, other shapes are possible. For example, it may be cylindrical, conical, etc. In general, it is desirable for the shape of the tip portion  226  to be such that it maximises heat transfer between the tip portion  226  and target tissue, in order to efficiently freeze the tissue. Therefore it may be desirable to use a shape which maximises contact area between the tip portion  226  and the target tissue. In some cases, the tip portion  226  may have a sharp tip so that it can pierce tissue and be inserted inside target tissue. In some examples the tip portion  226  and dielectric tip  214  may be or form part of a common tip structure for the device  200 . 
     The distal end of the electrosurgical device  200  may also include a sensor  238  located near the radiating tip portion  205 , for measuring a property of tissue in a treatment zone around the radiating tip portion. Measurements can be obtained from the sensor  238  via wiring  240 . For example, the sensor  238  may be a temperature sensor for measuring a temperature of tissue in the treatment zone. The sensor  238  may also be a pressure sensor, for measuring a change in pressure in the treatment zone. Measurements from the sensor  238  may be used to determine when tissue in the treatment zone is frozen, in order to determine when to apply microwave energy to the treatment zone. 
     In some embodiments, the electrosurgical device  200  may also include an outer sheath in which the components at the distal end of the device are housed. The outer sheath may have an aperture through which the tissue-freezing element  220  may protrude. The outer sheath may have a smooth shape so that no sharp corners are presented to biological tissue, in order to avoid accidental injuries. 
       FIG. 3  is a schematic cross-sectional view of a distal end of an electrosurgical device  300  that is another embodiment of the invention. In this embodiment, the cryogenic instrument is integrated into the electrosurgical instrument. The electrosurgical device  300  includes a coaxial feed cable  301 , which can be connected at its proximal end to a generator (e.g. generator  102 ) in order to convey microwave energy. The coaxial feed cable  301  comprises an inner conductor  303 , which is separated from an outer conductor  304  by a first dielectric material  306 . The coaxial feed cable  301  is preferably low loss for microwave energy. A choke (not shown) may be provided on the coaxial cable to inhibit back propagation of microwave energy reflected from the distal end and therefore limit backward heating along the device. 
     The coaxial feed cable  301  terminates at its distal end with a radiating tip portion  302  for radiating microwave energy. In this embodiment, the radiating tip portion  302  comprises a distal conductive section  308  of the inner conductor  303  that extends before a distal end  309  of the outer conductor  304 . The inner conductor  303  is hollow, with an inner surface of the inner conductor defining a channel  312  running through the inner conductor  303 . The distal conductive section  308  is surrounded at its distal end by a dielectric tip  310  formed from a second dielectric material, which is different from the first dielectric material  306 . The dielectric tip  310  is dome-shaped and has a channel running through it, and through which the inner conductor  303  passes. An aperture  314  is formed at the distal end of the inner conductor  303 . 
     The channel  312  may be connected at a proximal end to a cryogen supply unit (e.g. cryogen supply unit  108 ), so that channel  312  may act as a cryogen conveying conduit of a cryogenic instrument. A nozzle  316  which is fluidly connected to the channel  312  is located near the aperture  314  of the inner conductor. The nozzle  316  is arranged to spray cryogen conveyed through the channel  312  towards a target site in front of the radiating tip portion  302  (i.e. to the right in  FIG. 3 ), as illustrated by dashed lines  318 . The nozzle  316  may for example be a slit valve, however other types of nozzle are also possible. The nozzle  316  is configured to prevent fluid from the target site from entering the channel  312 , and so may include a one-way valve. In some embodiments, the nozzle  316  may include a fine tube in order to provide a concentrated and directed cryogen spray. In some embodiments, the nozzle  316  may be slidable in the channel  312  (e.g. using one or more control wires), so that the nozzle can be made to protrude beyond the radiating tip portion  302 . This way the nozzle  316  may be retracted when the electrosurgical device  200  is being guided into position, and then it may be deployed to spray target tissue. 
     The electrosurgical device  200  further includes a decompression tube  320 , through which gas in a treatment zone surrounding the radiating tip portion  302  may escape. This avoids pressure build-up in the treatment zone, which could lead to internal damage to the patient. In the case where the cryogen is a cold gas, cold gas sprayed from the nozzle  316  may cool tissue in the treatment zone and then exit the treatment zone via the decompression tube  320 . In the case where the cryogen is a cryogenic liquid, cryogenic liquid sprayed from the nozzle  316  may cool tissue in the treatment zone and expand into a gas. The resulting gas may then exit the treatment zone via the decompression tube  320 . 
     Preferably the decompression tube  320  is configured so that gas may only flow from the distal end of the electrosurgical device  200  (i.e. from the treatment zone) to the proximal end of the electrosurgical device  200 . This is to avoid gas entering the treatment zone via the decompression tube  320 . The decompression tube  320  may vent to atmosphere at its proximal end, or it may be connected to a gas collection chamber. The decompression tube  320  may also be fitted with a pressure relief valve, which is configured to allow gas to flow along the decompression tube  320  when pressure in the treatment zone reaches a predetermined threshold. In this manner, the pressure in the treatment zone may be maintained at a safe level. 
     The first dielectric material  306  may be a thermally insulating material, or may include a thermally insulating layer, so that the outer conductor  304  is not cooled by cryogen in the channel  312 . In this manner the outer surface of the coaxial feed cable  301  will not become cold when cryogen is run through the channel  312 , thus avoiding the risk of freezing parts of the patient outside the treatment zone. Alternatively, the coaxial feed cable  301  may include a thermally insulating sleeve and/or a vacuum jacket around the outer surface of the outer conductor  304 . 
     Cryogen running through the channel  312  may cool the inner conductor  303  and dissipate heat generated by any microwave energy propagated through the coaxial feed cable  301 . This enables the amount of microwave energy carried by the coaxial feed cable  301  to be increased without overheating the coaxial feed cable  301 . The configuration shown in  FIG. 3  therefore enables larger amounts of microwave energy to be applied, which may increase the volume of tissue ablated by the microwave energy. 
     The electrosurgical device  300  may also include one or more sensors and/or a heater, similar to those discussed in relation to  FIG. 2 . 
     It should be noted that different combinations of features from the embodiments shown in  FIGS. 2 and 3  are possible, with the embodiments shown in  FIGS. 2 and 3  being given merely by way of example. For example, the cryogenic instrument  202  of  FIG. 2  may be inserted through a hollow inner conductor of an electrosurgical instrument similar to that shown in  FIG. 3 . In this manner, the cryogen conveying conduit  224 , exhaust conveying conduit  228  and tissue-freezing element  220  may be contained within a channel similar to channel  312 , such that the cryogenic instrument  202  is fully integrated into the electrosurgical instrument. In another example, the cryogenic system  202  of  FIG. 2  may be replaced by a cryogen-spraying mechanism including a nozzle and a decompression tube similar to those described in relation to  FIG. 3 . 
       FIG. 4A  shows a schematic illustration of biological tissue ablation using an electrosurgical device according to the invention. The distal end of an electrosurgical device  400 , such as those described in relation to  FIGS. 2 and 3 , is inserted into target tissue which is to be ablated. Using the cryogenic instrument of the electrosurgical device  400 , a volume of tissue  402  around the distal end of the electrosurgical device  400  is frozen. This is done by flowing a cryogen through the cryogen conveying conduit to a tissue-freezing element at the distal end of the electrosurgical device  400 . Where the electrosurgical device in  FIG. 2  is used, the reservoir  222  may be filled with cryogen to cool the tip portion  226  of the tissue-freezing element  220 . The tissue-freezing element  220  may then be slid out of the thermally insulating sleeve  234  so that it comes into contact with the target tissue and causes the volume of tissue  402  to freeze. Where the electrosurgical device in  FIG. 3  is used, cryogen from the cryogen conveying conduit may be sprayed onto the target tissue to freeze the volume of tissue  402 . The volume  402  of tissue which is frozen may depend on the flow rate of cryogen through the cryogen conveying conduit and/or the temperature of the tissue-freezing element (which in some embodiments may be controlled using a heater). 
     Once the volume of tissue  402  is frozen, microwave energy is delivered to the radiating tip portion of the electrosurgical instrument so that microwave energy is applied to the frozen tissue. The microwave energy is transmitted with relatively low loss through the volume  402  of frozen tissue and into a surrounding layer of non-frozen tissue  404 , as indicated by arrows  406 . The microwave energy rapidly dissipates as heat in the layer of tissue  404 , causing ablation of the layer of tissue  404 . While the layer of tissue  404  is being ablated, the volume of tissue  402  may be kept frozen, e.g. by maintaining a constant flow of cryogen through the cryogen conveying conduit and/or controlling the temperature of the tissue-freezing element. 
     The state of the tissue (e.g. frozen or non-frozen) surrounding the distal end of the electrosurgical device  400  may be determined by measuring various properties of the tissue. For example, using one or more sensors mounted near the distal end of the electrosurgical device  400 , temperature and/or pressure can be measured to give an indication of whether the tissue is frozen. The electrosurgical instrument may be used to measure the impedance of the tissue surrounding its distal end, and thus determine whether the tissue is frozen. The impedance measurement may also be used to estimate the volume of tissue around the distal end which is frozen. Impedance of the tissue may be measured by sending a pulse of microwave energy down the coaxial feed cable to the radiating tip portion and measuring any microwave energy reflected back up the coaxial feed cable. 
     Once the tissue in layer  404  has been ablated, the tissue in volume  402  may be gradually allowed to thaw so that it can be progressively ablated by applied microwave energy. The tissue can be allowed to thaw by reducing the flow of cryogen through the cryogen conveying conduit and/or increasing the temperature of the tissue-freezing element (e.g. using a heater mounted thereon). By appropriately controlling the flow of cryogen through the cryogen conveying conduit and/or the temperature of the tissue-freezing element, the volume of tissue which is frozen may be reduced in stages. At each stage, microwave energy may be applied to ablate a layer of tissue surrounding the frozen tissue which was previously frozen. 
     This process is illustrated in  FIG. 4B . Initially, tissue layers  414 ,  412  and  410  are frozen, so that outer layer  408  may be ablated when microwave energy is applied to the frozen tissue. Then, layer  410  is allowed to thaw, keeping layers  414  and  412  frozen, such that layer  410  may be ablated by microwave energy. Layer  412  is then thawed, so that it may also be ablated. Finally, the innermost layer  414  is thawed and ablated by direct application of microwave energy. In this manner, the total volume of tissue which can be ablated is defined by an outer surface of the layer of tissue  408 . This volume may be much greater than the volume of tissue which can be ablated by applying the same amount of microwave energy directly to non-frozen tissue. 
     A controller may be used to control the various steps in the ablation process. The controller may be configured to obtain measurements from one or more sensors located near the distal end of the electrosurgical instrument in order to determine whether tissue in a treatment zone around the radiating tip portion of the electrosurgical instrument is frozen. The controller may also be configured to carry out impedance measurements to determine if the tissue in the treatment zone is frozen. Depending on the result of the determination, the controller may be configured to adjust the flow of cryogen in the cryogen conveying conduit and/or the temperature of the tissue-freezing element (e.g. to increase or decrease the volume of frozen tissue in the treatment zone). Once it is determined that a desired volume of tissue has been frozen, the controller may be configured to deliver microwave energy to the radiating tip portion. The controller may also be configured to successively ablate tissue layers as described in relation to  FIG. 4B . 
     The controller may be a conventional computing device having software installed thereon for carrying out the various steps described above. The computer may be connected to the generator  102 , so that it can control the supply of microwave energy to the radiating tip portion of the electrosurgical instrument. The computer may also be connected to the cryogen supply unit  108  to control the flow of cryogen through the cryogen conveying conduit (e.g. by controlling a valve in the cryogen supply unit  108 ). Outputs from any sensors on the electrosurgical device may be connected to the controller, so that it can obtain measurements from the sensors. If a heater is disposed on the electrosurgical apparatus, its input may also be connected to the controller. In this manner the controller provides an automated system for performing tissue ablation.