Abstract:
The invention describes a system and method for revitalizing aging skin using electromagnetic energy that is delivered using a plurality of needles that are capable of penetrating the skin to desired depths. A particular aspect of the invention is the capability to spare zones of tissue from thermal exposure. This sparing of tissue allows new tissue to be regenerated while the heat treatment can shrink the collagen and tighten the underlying structures. Additionally, the system is capable of delivering therapeutically beneficial substances either through the penetrating needles or through channels that have been created by the penetration of the needles.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]     This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application Ser. No. 60/741,031, “Method and apparatus for micro-needle array electrode treatment of tissue,” filed Nov. 29, 2005. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     1. Field of the Invention  
         [0003]     This invention relates generally to biological tissue treatment using electromagnetic energy delivered through an array of needle electrodes. More particularly, it relates to using radio frequency energy through an array of microneedles for rejuvenating human skin by a fractional treatment.  
         [0004]     2. Description of the Related Art  
         [0005]     Skin is the primary barrier that withstands environmental impact, such as sun, cold, wind, etc. Along with aging, environmental factors cause the skin to lose its youthful look and develop wrinkles. Human skin is made of epidermis, which is about 100 μm thick, followed by the dermis, which can extend up to 4 mm from the surface and finally the subcutaneous layer. These three layers control the overall appearance of the skin (youthful or aged). The dermis is made up of elastin, collagen, glycosoaminoglycans, and proteoglycans. The subcutaneous layer also has fibrous vertical bands that course through it and represent a link between dermal collagen and the subcutaneous layer. The collagen fibers provide the strength and elasticity to skin. With age and sun exposure, collagen loses its elasticity (tensile strength) and skin loses its youthful, tight appearance. Not surprisingly, numerous techniques have been described for rejuvenating the appearance of skin.  
         [0006]     One approach to skin rejuvenation is to physically inject collagen into the skin. This gives an appearance of fullness or plumpness and the offending lines are smoothened. Bovine collagen has been used for this purpose. Unfortunately, this is not a long-lasting or complete fix for the problem and there are frequent reports of allergic reactions to the collagen injections.  
         [0007]     It is now well established that collagen is sensitive to heat treatment and denatures when heated above its transition temperature. This denaturing is accompanied by shrinking of the collagen fibers and this shrinking can provide sagging or wrinkled skin with a tightened youthful appearance. Both heat and chemical based approaches have been described and used to shrink collagen.  
         [0008]     Peeling most or all of the outer layer of the skin is another known method of rejuvenating the skin. Peeling can be achieved chemically, mechanically or photothermally. Chemical peeling is carried out using chemicals such as trichloroacetic acid and phenol. An inability to control the depth of the peeling, possible pigmentary change, and risk of scarring are among the problems associated with chemical peeling.  
         [0009]     All the above methods suffer from the problem of being invasive and involve significant amount of pain. As these cosmetic procedures are all generally elective procedures, pain and the occasional side effects have been a significant deterrent to many, who would otherwise like to undergo these procedures.  
         [0010]     To overcome some of the issues associated with the invasive procedures, laser and radio frequency energy based wrinkle reduction treatments have been proposed. For example, U.S. Pat. No. 6,387,089 describes using pulsed light for heating and shrinking the collagen and thereby restoring the elasticity of the skin. Since collagen is located within the dermis and subcutaneous layers and not in the epidermis, lasers that target collagen must penetrate through the epidermis and through the dermal epidermal junction. Due to Bier&#39;s Law absorption, the laser beam is typically the most intense at the surface of the skin. This results in unacceptable heating of the upper layers of the skin. Various approaches have been described to cool the upper layers of the skin while maintaining the layers underneath at the desired temperature. One approach is to spray a cryogen on the surface so that the surface remains cools while the underlying layers (and hence collagen) are heated. Such an approach is described in U.S. Pat. No. 6,514,244. Another approach described in U.S. Pat. No. 6,387,089 is the use of a cooled transparent substance, such as ice, gel or crystal that is in contact with the surface the skin. The transparent nature of the coolant would allow the laser beam to penetrate the different skin layers.  
         [0011]     To overcome some of the problems associated with the undesired heating of the upper layers of the skin (epidermal and dermal), U.S. Pat. No. 6,311,090 describes using RF energy and an arrangement comprising RF electrodes that rest on the surface of the skin. A reverse thermal gradient is created that apparently does not substantially affect melanocytes and other epithelial cells. However, even such non-invasive methods have the significant limitation that energy cannot be effectively focused in a specific region of interest, say, the dermis.  
         [0012]     Other approaches have been described to heat the dermis without heating more superficial layers. These involve using electrically conductive needles that penetrate the surface of the skin into the tissue and provide heating. U.S. Pat. Nos. 6,277,116 and 6,920,883 describe such systems. Unfortunately, such an approach results in widespread heating of the subcutaneous layer and potentially melting the fat in the subcutaneous layer. This leads to undesired scarring of the tissue.  
         [0013]     One approach that has been described to limit the general, uniform heating of the tissue is fractional treatment of the tissue, as described in published U.S. Patent Application 20050049582. This application describes the use of laser energy to create treatment zones of desired shapes in the skin, where untreated, healthy tissue lies between the regions of treated tissue. This enables the untreated tissue to participate in the healing and recovery process.  
         [0014]     Hence, it will be desirable to accomplish the fractional or patterned heat generation in the epidermis, dermis or subcutaneous layers of the skin using needles or microneedles that could be located at the desired depth in the skin.  
       SUMMARY OF THE INVENTION  
       [0015]     The invention describes improved methods and systems for rejuvenating aging skin to achieve cosmetically desirable outcomes by shrinking collagen using radio frequency energy that is delivered to the target sites using a microneedle electrode array.  
         [0016]     The invention provides a dermatological treatment apparatus for selectively treating zones of tissue within the skin. Such selective tissue treatment is achieved using an array of electrically conductive microneedles that are connected to a radio frequency energy source. The RF energy source is operated by a controller unit, which is programmable and is capable of activating a selected group of needle electrodes. This programmable selectivity leads to a desired pattern of microneedle electrodes treating zones of tissue at the desired location in the skin and simultaneously sparing tissue that is surrounding the targeted zones.  
         [0017]     The controller unit has the capability of monitoring changes in the tissue parameters, such as conductivity and temperature, and uses these measurements to determine when treatment should be terminated. Additionally, the tissue property measurements can identify sensitive zones, such as nerves, to be excluded from the thermal treatment.  
         [0018]     The microneedles can also be hollow and thereby are capable of delivering desirable therapeutic agents to the treated zones. The therapeutic agents could include anesthetics, growth factors, stem cells, botulinum toxin, etc.  
         [0019]     In another embodiment, the microneedles are driven into the tissue using mechanical energy, where such driving force could be vibration or pressure. In another aspect of this invention, the treatment device has a suction coupling such that the each microneedle penetration depth could be individually controlled. This is highly desirable in anatomical regions containing uneven contours, such as the face and the transition areas from the face to the neck.  
         [0020]     In yet another embodiment of this invention, the controller has algorithms embedded in it, which identifies the appropriate needle pair(s) that needs to be activated so that there is enough thermal relaxation time at the treated zones and thereby avoiding overheating of the treated zones and maintaining the desired temperature of the untreated tissue surrounding the treated zones.  
         [0021]     Additional features and advantages of the invention described in the drawings and the description below and in the appended claims. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0022]     The invention has other advantages and features which will be more readily apparent from the following detailed description of the invention and the appended claims, when taken in conjunction with the accompanying drawings, in which:  
         [0023]      FIG. 1  is a diagram showing an embodiment of the invention wherein a handpiece is placed in contact with the skin. Vacuum channels are used to make reproducible contact with the skin surface and to force the needles into the skin. RF energy is delivered to the skin through the needles to form fractional treatment zones. Cryogenic spray is used to cool the needles and/or the contact plate to prevent overheating of selected tissue.  
         [0024]      FIG. 2  is a diagram showing details of the vacuum channel in the area around the needle array.  
         [0025]      FIG. 3  shows wiring diagrams of the needle electrode array for two embodiments of the invention.  FIG. 3A  shows a wiring pattern where only two source electrodes are used.  FIG. 3B  shows a wiring pattern where multiple source electrodes are used such that each electrode is wired individually.  
         [0026]      FIGS. 4 and 5  are treatment patterns that can be created using either of the wiring patterns shown in  FIGS. 3A and 3B .  FIGS. 4A and 5A  show treatment patterns and the electrodes.  FIGS. 4B and 5B  show the corresponding treatment patterns after the electrodes have been removed from the skin. The treatment pattern in  FIG. 4B  is discontinuous. The treatment pattern in  FIG. 5B  is continuous.  
         [0027]      FIGS. 6 and 7  show treatment patterns that can be created using the wiring pattern shown in  FIG. 3B .  FIGS. 6A and 7A  show treatment patterns and the electrodes.  FIGS. 6B and 7B  show the corresponding treatment patterns after the electrodes have been removed from the skin.  
         [0028]      FIGS. 8 and 8 A show a treatment pattern that is used to treat an unwanted blood vessel.  
         [0029]      FIGS. 9A and 9B  show a treatment pattern that can be created using either of the wiring patterns shown in  FIGS. 3A and 3B , if the device is elongated in one direction of the array relative to the other.  FIG. 9A  shows a treatment pattern and the electrodes.  FIG. 9B  shows the corresponding treatment pattern after the electrodes have been removed from the skin.  
         [0030]      FIG. 10  is a diagram of the lines of maximum extensibility for the face. Treatment can be performed along the lines of maximum extensibility to enhance the treatment appearance.  
         [0031]      FIG. 11  is a diagram of an embodiment of the invention wherein the micro needles have shallow penetration.  
         [0032]      FIG. 12  is a diagram of an embodiment of the invention wherein the micro needles are hollow to allow delivery of a substance into the skin tissue.  
         [0033]      FIG. 13  is a diagram of an embodiment of the invention wherein the depth of the needles can be adjusted by adjusting the space between two plates. In this embodiment, the needles may be pushed into the skin with the assistance of vacuum.  
         [0034]      FIGS. 14A and 14B  show an embodiment of the invention that comprises a removable tip that attaches to a handpiece.  
         [0035]      FIGS. 15A and 15B  show histology sections of human skin stained with hemotoxylin and eosin following ex vivo treatment with RF energy delivered using a microneedle electrode array.  FIG. 15A and 15B  represent different pulse conditions for the pulse source and the needle positions. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0036]      FIG. 1  illustrates an embodiment of the invention. In this embodiment, a radio frequency (RF) source  110  is connected to an array of needles  115  that are mounted on a contact plate  105 . The RF source  110  generates energy that is delivered to the tissue to create treatment zones  160  within the skin  150 . A vacuum apparatus or suction apparatus  125  is attached to a vacuum port  120  of the contact plate  105 . A handpiece  100  is used by the practitioner to control the location of the device on the skin and deliver RF energy to the desired location for treatment. A cryogenic spray  140  is used to cool the contact plate  105  and/or the needles  1   15 . A vibrating element  135  is mechanically coupled to the contact plate  105 . A vibration power source  130  is preferably located external to the handpiece  100  and is connected to the vibrating element  135  to power the vibrating element  135 , which in turn would drive the needles  115  into the skin, as the vibrating element  135  is mechanically coupled to the contact plate  105  on which the needles are mounted.  
         [0037]     The handpiece  100  can be applied to the surface of the skin  150 . This causes the needles  115  to penetrate the surface of the skin  150 . The skin  150  may have significant wrinkles or other topology. Therefore, the needles may not all penetrate to the same depth within the skin. In some embodiments of the invention, it is preferable that all of the needles penetrate to a predetermined depth within the skin  150 . Preferably, the needles are arranged to primarily deliver treatment in the papillary dermis and/or the upper reticular dermis. A vacuum port  120  can be attached to a vacuum apparatus  125 . The vacuum apparatus  125  creates a negative pressure within the vacuum channels  123  (as shown in  FIG. 1 ) so that the surface of the skin  150  is drawn into contact with the contact plate  105  and the needles  115  penetrate into the skin  150  to a predetermined depth beneath the surface of the skin  150 . The vibrating element  135  can be powered by the vibration power source  130  to help the needles  115  penetrate into the skin  150  more easily by vibrating the contact plate  105  and/or the needles  115 . While the needles  115  are located within the skin  150 , they can be powered by the RF source  110  to create an array of treatment zones  160  through resistive heating of the tissue. In some embodiments, it may be desirable to avoid or limit treatment of the epidermis  152  or selected upper layers of the skin  150 , which can be accomplished by cooling the back of the contact plate  105  with a cryogenic spray  140 . It may also be desirable to limit the penetration depth of the needles such that the needles do not penetrate into the layer of subcutaneous fat  154  because melting of the fat layer can lead to scarring due to fat atrophy. Melting of the subcutaneous fat  154  also reduces the skin thickness which may not be desirable. The contact plate  105  can be thermally conductive to carry the heat away from the skin  150  during or following treatment.  
         [0038]     Cryogenic spray cooling  140  may be used to actively cool the contact plate  105  to enhance the cooling of the skin  150 . A cryogenic spray cooling  140  may also be used to cool the surface of the skin  150  directly by spraying cryogen onto the surface of the skin  150 . The cryogenic spray  140  could be a container containing a cryogen, such as, for example, compressed tetrafluoroethane.  
         [0039]     In an alternate embodiment (not shown), the contact plate  105  may be cooled by circulating a liquid at room-temperature or chilled liquid to make thermal contact to the contact plate  105 . The cooling fluid can conductively cool the needles  115  and/or the contact plate  105 , which lowers the temperature of the skin  150  relative to the temperature that would be achieved without cooling. Cooling of the skin  150 , when desired, can thus be used to avoid heating or over heating of the epidermis  152  or upper layers of the skin  150 .  
         [0040]     In a preferred embodiment, the needles  115  are  36 -gauge electrically conductive needles that are connected to the RF source  110 . The needles  115  could be prepared by cutting commercially available long hypodermic needles. The needles  115  can be soldered onto a circuit board where the circuit board is patterned, as shown in the patterns of  FIG. 3 , to create an array of wired needles  115  that can be used according to this invention. The circuit board can be single or multilayered.  
         [0041]     Preferably, the needles  115  are pointed and made of a solid conductive material such as, for example, metal. The needles  115  may also be hollow or made of an electrically nonconductive material that has a conductive coating. In some embodiments, each of the needles  115  can comprise an electrically conductive shaft or coating that is coated on the surface with an electrically non-conductive material such as, for example, Teflon. An electrically non-conductive coating material can be patterned in order to channel the RF treatment energy to a particular location where the electrically conductive shaft or coating contacts the skin through a gap in the patterned electrically non-conductive coating. In a preferred embodiment, the needles  115  are 50 to 300 μm in diameter. The diameter of the needles  115  is preferably at least 50 μm to reduce breakage of the needles  115 . The diameter of the needles  115  is preferably less than 300 μm to allow close packing of the needles  115  and to reduce disruption to the skin  150  and purpura, as the needles  115  penetrate into the skin  150 . The needles are also described as microneedles and when connected to an RF energy source as a microneedle electrode array.  
         [0042]     The RF source  110  can be a radio frequency or microwave source that is used to create a temperature increase in the tissue when used with the needles  115 . The RF source  110  may be bipolar or monopolar. Preferably, these sources operate in a frequency range used for industrial applications so that cheaper electromagnetic sources are available. For example, the frequency of the RF source can be chosen to be about 6.78 MHz or about 13.56 MHz. In some preferred embodiments, the frequency range is from 0.1 to 10 MHz or from 0.4 to 3 MHz. The resistance of the skin varies with the frequency of RF source. The frequency range of the RF source can be chosen based on the desired treatment zone profile including for example treatment zone size, treatment zone shape, treatment zone aspect ratio, and treatment zone spacing.  
         [0043]     In a preferred embodiment, the vacuum channels  123  are machined into the contact plate  105 . The contact plate  105  is preferably electrically-insulating to prevent shorting between the needles while providing physical support for the needles. An electrically insulating material that could be used in some embodiments is alumina. A vacuum port  120  connects to the vacuum channels  123  to create a negative pressure in the vacuum channels  123  when the vacuum port  120  is connected to the vacuum apparatus  125 . In a preferred embodiment, the vacuum port  120  is a hose fitting to which a vacuum hose is attached to connect the vacuum channels  123  to the vacuum apparatus  125 . The vacuum apparatus  125  can be, for example, a vacuum pump.  
         [0044]     In a preferred embodiment, the vibrating element  135  is a piezo-electric vibrating unit or an electrical buzzer and the vibration power source  130  is an electrical source that is matched to the vibrating element  135 .  
         [0045]     The treatment zones  160  are shown in  FIG. 1  to be located within the dermis  153 , but these treatment zones may also be located within the epidermis  152 , at the dermal-epidermal junction, or treatment zones may include regions in both the epidermis  152  and dermis  153 .  
         [0046]     The treatment pattern created by the treatment zones  160  can depend, for example, on the distribution of the needles  115 , on the wiring patterns for the needles  115 , and/or on the firing pattern of the needles  115  by the RF source  110 . The array of treatment zones  160  that is created according to the invention may be regular or irregular. It will typically be easier to design and build an apparatus using automated manufacturing techniques if the array of treatment zones  160  is regular. Creating irregular arrays of treatment zones  160  will reduce the visual impact due to treatment by making the treatment appear more natural since many natural features vary in an irregular manner within the skin  150 .  
         [0047]     The vacuum channels  123  shown in  FIG. 1  can be arranged according to the desired treatment application. A preferred embodiment for the geometry of the vacuum channels  123  of  FIG. 1  is shown in  FIG. 2 . In this embodiment, the vacuum channels  123  comprise an outer vacuum ring  122 , vacuum feeder lines  124 , and individual needle-specific vacuum rings  121 . In  FIG. 2 , negative pressure created within the outer vacuum ring  122  holds the skin to the contact plate  105  shown in  FIG. 1  to hold the skin  150  and contact plate  105  in contact as shown in  FIG. 1 . The outer vacuum ring  122  creates a more uniform application of force by the individual needle-specific vacuum rings  121 . In this embodiment, the vacuum feeder lines  124  are not typically in contact with the skin  150 , but they can be. The vacuum feeder lines  124  are used to connect the vacuum port  120  to the outer vacuum ring  122  and to the individual needle-specific vacuum rings  121 .  
         [0048]     Individual needle-specific vacuum rings  121 A-C wrap around each of the needles  115 A-C in the array. The negative pressure created within each of the needle-specific vacuum rings  121  forces the skin  150  onto the encircled needle such that the encircled needle penetrates to a predetermined depth in the skin  150 .  
         [0049]     The RF source  110  shown in  FIG. 1  may be wired to the needles  1   15  in different patterns that may be chosen based on the desired application. A preferred embodiment of the wiring pattern is shown in  FIG. 3A . In  FIG. 3A , the RF source  110  has two output terminals. One of the output terminals is labeled with a plus sign (active) and the other with a minus sign (return) to indicate two poles of the RF source  110 . Alternate interleaved rows of the array are wired to either the plus or the minus electrode through the common wiring buses  111  and  112 . Thus, two interleaved arrays of regularly spaced needles  115  are formed. One array includes all of the negative polarity needles  116  (return electrodes) and the other includes all of the positive polarity needles  117  (active electrodes). In  FIG. 3 , the negative needles  116  are open and the positive needles  117  are shaded.  
         [0050]     The spacing between the negative needles  116  and the positive needles  117  can be chosen, for example, based on the resistance of the skin at the frequency of the RF source  110  such that the pulsing of the RF source  110  creates a treatment zone  160  between nearest neighbors within the array of needles  115 .  
         [0051]     Note that needles  115  can be described generally as needles  115  or they can be further categorized as positive polarity needles  117  (shaded in  FIGS. 3-9 ) and negative polarity needles  116  (unshaded in  FIGS. 3-9 ). Positive needles  117  and negative needles  116  are subsets of the general category of needles  115 . Positive and negative polarities refer to opposite poles of the RF source.  
         [0052]     In an embodiment, the array of needles  115  comprises at least sixteen needles  115 . The use of at least sixteen needles makes the treatment proceed faster than with fewer needles and also helps to reduce the torque that may be applied to each needle which could tear the skin  150 .  
         [0053]      FIGS. 4A and 4B  show a treatment pattern  161  of treatment zones  160  that can be produced from either of the wiring patterns shown in  FIG. 3A  or  3 B.  FIG. 4A  shows the treatment zones  160  that are created between nearest neighbor needles  115  that are connected to opposite poles of the RF source  110 .  FIG. 4B  shows the corresponding treatment pattern  161  of  FIG. 4A  after the needles have been removed from the skin  150 . The treatment pattern  161  is an example of a discontinuous treatment pattern  161  of treatment zones  160 .  
         [0054]     With the proper choice of parameters, the treatment can be self limiting to create treatment zones  160  of approximately uniform size across the treatment pattern  161 . The self limiting nature of the treatment can be achieved by choosing the frequency of the RF source  110  to be a frequency for which the tissue resistivity (impedance) increases as the tissue is treated. As skin  150  is treated, the water content of the treatment zone  160  is reduced, which typically increases the resistivity of the treatment zone  160  relative to the surrounding skin  150 .  
         [0055]     At high RF pulse energies and/or close spacing of the array of needles  115 , the treatment zones  160  can be created such that the treatment zones  160  merge together to form a continuous treatment pattern  162  as shown in FIGS. SA and  5 B. The continuous treatment pattern  162  can be created using either the wiring pattern shown in  FIG. 3A  or  3 B.  
         [0056]      FIGS. 6 and 7  show other treatment patterns  163  and  164  that can be created using the wiring pattern shown in  FIG. 3B . In these embodiments, not all of the electrode pairs are activated. The treatment patterns  163  and  164  differ in the timing between pulsing of electrode pairs to create each treatment zone  160  and in which electrode pairs are pulsed.  
         [0057]     In an alternate embodiment, the needles are connected to an RF switching network such that the polarity of each needle  115  can be selected for each pulse of the RF source  110 . Selected needles  115  may also be floated or grounded by the switching network to create other treatment patterns. The array of needles  115  can thus be reconfigurable. A reconfigurable array of needles  115  can be used to actively target features within tissue. For example, a CCD camera or visual observation port can be used to identify the position of a blood vessel  180  to be treated within the skin  150 . As shown in  FIGS. 8A and 8B , once the blood vessel  180  has been identified, selected needle pairs can be fired to treat or to spare the identified blood vessel  180 . Other identifiable objects within or on the skin  150  can be targeted or spared using a reconfigurable array of needles  115 . For example, sebaceous glands, tattoos, wrinkles, scars, hairs, hair follicles, and pigmented lesions may be targeted using reconfigurable arrays of needles  115 . Another example of a reconfigurable array of needles  115  is an individually addressable needle system as shown in  FIG. 3B  where the RF source  110  can individually address each needle or selected sets of needles within in the array. Apart from visual identification, structures such as blood vessels could also be identified by commonly known techniques. One such technique would be an impedance sweep of the tissue.  
         [0058]      FIG. 9  shows an arrangement of the needles  115  in which the treatment pattern  165  is elongated due to a different arrangement of the needles  115 . Also illustrated in this example is the use of needles  115  with oval cross sections, which can be used to create more localized electrical field profiles within the tissue or to create a discontinuous treatment pattern  161  as shown in  FIG. 4B . Oval cross sections can also be used to reduce local fields and thus reduce charring and over-treatment.  
         [0059]     Each treatment zone  160  can be created by electrically connecting the needles  116  and  117  at the opposite ends of each local region of skin  150  to be treated to different poles of the RF source  110 . One or more treatment zones  160  within any of the treatment patterns  161 - 166  can be created either sequentially or simultaneously depending on the desired application. Sequential creation of treatment zones  160  is useful in situations where minimizing thermal crosstalk is important or where the power of the RF source  110  is limited. Simultaneous creation of treatment zones  160  is useful in situations where treatment speed is important.  
         [0060]     Each of the treatment patterns  161 - 166  desirably spares healthy tissue between the treatment zones  160 . Sparing of healthy tissue between treatment zones  160  reduces the incidence of scarring and promotes rapid healing by allowing nutrients, cells, and cytokines to flow more quickly to the wounded areas to stimulate the wound healing response. The spared tissue also allows transport to the dermal-epidermal junction and the epidermis so that the epidermis can remain healthy or heal quickly following treatment.  
         [0061]     The treatment patterns  161 - 166  are shown here as examples of treatments that can be created performed according to the invention. Other patterns can be used to create different effects based on particular applications.  
         [0062]     The treatment pattern  164  shown in  FIGS. 7A and 7B  is particularly useful because it can create a line of tension within the skin  150  due to collagen denaturation. Collagen denaturation causes collagen fibers to shrink in length by up to approximately 60% or 70% and thus can provide considerable tension along a particular direction. To enhance the appearance of shrinkage on the skin, the treatment can preferably be aligned to cause shrinkage along the directions of maximum extensibility. The lines of maximum extensibility  159  are illustrated in  FIG. 10 . Arranging treatment along the lines of maximum extensibility  159  will be helpful for reducing the visibility of wrinkles.  
         [0063]      FIG. 11  shows an embodiment of the invention in which needles  115  penetrate primarily to predetermined depths within the epidermis  152  such that treatment zones  160  are created in the epidermis  152  and/or along the dermal-epidermal junction located at the base of the epidermis  152 . To limit the penetration to only the epidermis, it may be desirable to limit the predetermined needle penetration depth to 5-50 μm.  
         [0064]      FIG. 12  shows an embodiment of the invention in which delivery needles  118  are hollow and open at the distal end. Delivery needles  118  can be physically connected to a fluid filled reservoir  170  that contains a therapeutic substance that is to be delivered beneath the surface of the skin into, for example, the epidermis  152 , dermis  153 , subcutaneous fat  154 , or muscular layers (not shown). Examples of therapeutic substances that can be delivered are anesthetics (such as lidocaine), vitamins (such as vitamin C), minerals, growth factors, pro-drugs, hormones, stem cells, vasoconstrictors, steroids, botulinum toxin, and photosensitive toxins. In an alternate embodiment, the needles can be made to be permeable so that therapeutic substances can be delivered through the permeable needles.  
         [0065]     Since the primary barrier for many topically applied therapeutic substances is the stratum corneum, which is the outermost layer of the epidermis, the delivery needles  118  can significantly enhance delivery of a therapeutic substance even if the delivery needles  118  only penetrate into the epidermis  152  and not into the dermis  153 .  
         [0066]     The delivery of botulinum toxin in combination with the RF treatment using a microneedle area is one embodiment, whereby the combination treatment of fractional RF tightening of tissue and local temporary paralysis of the underlying muscles through the use of botulinum toxin is effective for treatment of wrinkles and the delay of recurrence of wrinkles.  
         [0067]     In an alternate embodiment, therapeutic substances can be applied to the surface of the skin  150  after treatment to cause the therapeutic substances to penetrate into the pores or channels created by needles  115  or  118 .  
         [0068]     In some embodiments, it may be desirable to use a high level of treatment to create large treatment zones or allow a large needle separation. In such embodiments, the skin may be charred or over-treated due to the local concentration of the electric field that occurs, for example, near the ends of the needles where the electric field may be highest. As shown in  FIG. 13 , the incidence of over-treatment or charring can be reduced by cooling the needles  115  using the cryogenic spray  140  by spraying directly onto a thermal mounting plate  107  that is thermally connected to the needles  115 . The embodiments that use this cooled needle approach can also reduce the occurrence of the skin  150  adhering to the surface of the needles  115  when the RF treatment is performed. The contact plate  105  may be thermally insulating or thermally conductive depending on the desired thermal profile for treatment. Chilling the needles  115  will help to reduce purpura in some applications.  
         [0069]     The contact plate  105  may be in thermal contact with the thermal mounting plate  107  to cool the surface of the skin  150  instead of or in addition to cooling the needles  115 . In another embodiment, the cryogenic spray  140  may also be directed to cool both the contact plate  105  and the thermal mounting plate  107  by patterning a first plate, which is either the contact plate or the thermal mounting plate  107 , such that part of the cryogen emanating from the cryogen spray  140  passes through patterned regions in the first plate to cool the second plate that lies beyond the first plate.  
         [0070]     In some embodiments, it may be desirable to use vacuum force to push the needles  115  into the skin  150  after good contact has been established between the contact plate  105  and the skin  150 . The embodiment shown in  FIG. 1  is a preferred embodiment, as it does not have many moving parts that can wear out. An alternate embodiment shown in  FIG. 13  provides better contact between the contact plate  105  and the skin  150  prior to the activation of the vacuum apparatus  125 .  
         [0071]     In  FIG. 13 , the vacuum apparatus  125  draws a negative pressure to create a force between the thermal mounting plate  107  and the contact plate  105 . The vacuum apparatus  125  is connected to the chamber between the thermal mounting plate  107  and the contact plate  105  via the vacuum port  120  and the vacuum feeder line  126 . The needles  115  can be attached to the thermal mounting plate  107 . As the chamber is pumped to a negative pressure, the force between the thermal mounting plate  107  and the contact plate  105  can be used to force needles  115  to a predetermined depth within the skin  150 . The adjustable spacer  106  may comprise bellows that can be expanded or compressed to create the desired offset to control the penetration depth of the needles. By adjusting the height of the adjustable spacer  106 , the predetermined depth of penetration of the needles  115  in the skin  150  can be adjusted.  
         [0072]      FIGS. 14A and 14B  show an embodiment of the invention that contains a disposable tip  199 . Delivery needles  118  are attached to a contact plate  105  for delivery of a therapeutic substance from the fluid filled reservoir  170 . Vacuum channels  123  are connected to two vacuum ports  120 A, and  120 B for connection to handpiece  200  that contains or attaches to a vacuum apparatus (not shown). The disposable tip  199  also comprises two electrical contact pads  111  and  112  for making electrical contact to two corresponding electrical contact pads  211  and  212  that are located on the handpiece  200 . The electrical contact pads  211  and  212  are connected to an RF source (not shown). The other end of the electrical contact pads  111  and  112  are connected to the delivery needles  118 . The tip  199  can be attached to a handpiece  200  using a magnetic latch  195  or by snap fitting or by other mechanical means. The needles  118  are surrounded by a vacuum curtain  190  that makes a vacuum seal with the skin (not shown) during treatment. Prior to use, the delivery needles  118  can be protected using a protective needle plug  191  that includes a plug handle  192  for removing the needle plug  191  from the delivery needles  118 .  
         [0073]     To use the tip  199  shown in  FIG. 14B  for treatment, the tip  199  is attached to the handpiece  200  using the magnetic latch  195 . The contact pads  111  and  112  make electrical contact to the corresponding electrical contact pads  211  and  212  on the handpiece  200 . The vacuum channels  223  attach to the vacuum ports  120  on the tip  199 . The protective needle plug  191  is removed using the plug handle  192 . The delivery needles  118  of the tip  199  are then applied to the skin (not shown) using manual pressure on the handpiece  200 . The vacuum curtain  190  would make an air tight seal with the skin. To help make the seal air tight, a vacuum compatible gel, grease, or sealant can be used. The vacuum apparatus (not shown) is activated to create a negative pressure between the contact plate  105  and the skin (not shown) to force the delivery needles  118  into the skin to a predetermined depth. The RF source (not shown) is then pulsed to create treatment zones (not shown) within the skin. Following treatment, the handpiece  200  is lifted from the skin to withdraw the delivery needles  118  and remove the tip  199  from the skin. The tip  199  can then be manually detached from the handpiece  200 .  
         [0074]     The vacuum curtain  190  can be made of vinyl and should be thin enough to flex without breaking when applied to the skin so that a good vacuum seal can be created.  
         [0075]     A fast-acting anesthetic in conductive saline solution can be added to the fluid-filled reservoir  170  for management of pain during or after the RF treatment. The use of conductive saline solution enlarges the electrical path for the RF treatment.  
         [0076]     The tip  199  can be sterilized, if materials are chosen that are compatible with sterilizers, such as stainless steel and high melting temperature plastics.  
         [0077]      FIG. 15  shows several treatment zones  260 ,  261  created using an ex vivo human tissue model. Excised human abdominal skin  150  was placed on a hot plate to heat the skin  150  to approximately body temperature prior to treating using an RF source  110  connected to a pair of needle probes  115 . Saline soaked gauze sheets were used to keep the skin tissue moist as it was being heated prior to treatment. Two needles  115  were used to demonstrate the treatment zones created by each needle pair  116  and  117 .  
         [0078]     Ex vivo tissue samples were frozen in optimal cutting temperature fluid (International Medical Equipment, Inc., San Marcos, Calif.) and were sliced with a cryostat into approximately 6-15 μm thick sections and stained with hematoxylin &amp; eosin (Harris Hematoxylin and Eosin Y stains from International Medical Equipment, Inc.). The sliced sections were placed on glass microscope slides, dehydrated in 95% alcohol, and rehydrated in deionized water. Samples were then stained with hematoxylin to dye nuclei and cytoplasm within cells and with eosin to dye connective tissue. The concentration of alcohol was adjusted to optimize the contrast visible in the slide. Xylene was used to rinse the slides prior to mounting a glass coverslip.  
         [0079]      FIG. 15A  shows the results of using of a needle pair that penetrated approximately 1-2 mm into the skin with a needle separation of 0.5 mm. A bipolar RF source operating at a frequency of 0.47 MHz, a power of 5W, and a pulse duration of 400 ms was used. The treatment zone  260  that was created has dimensions of approximately 500 μm width and 600 μm height. The aspect ratio of width to height of the treatment zone  260  is therefore approximately 5:6.  
         [0080]     For  FIG. 15B , the conditions were similar to those for  FIG. 15A  except the pulse duration was 200 ms, the separation between the needles  115  was 1 mm, and the depth of needle penetration was approximately 0.5-1 mm. The treatment zone  261  that was created has dimensions of approximately 900 μm width and 250 μm height. The aspect ratio of width to height for the treatment zone  261  is therefore approximately 3.6:1.  
         [0081]     Other pulse parameters could be used. A preferred pulse source frequency is 0.47 MHz, but other frequencies can be used as described above. Other frequencies are particularly useful to create treatment zones of different shapes because the material resistivity of the skin is frequency dependent. Therefore, different frequencies will create different treatment zone shapes for otherwise equivalent pulse conditions. For each electrode pair that is fired to create treatment zones between the electrode pair, the pulse energy from the RF source  110  is preferably 0.1 to 8.0 J and more preferably in the range of 0.5 to 2.0 J. Pulse energies in the range of 0.02 to 0.10 J can be used in cases where needles are spaced close together. Preferably, the aspect ratio of width to height for the treatment zones  160  is in the range of 1:2 to 5:1 and more preferably in the range 2:1 to 4:1. Treatment zones  160  with an aspect ratio of width to height of greater than 1:1 are called “lateral treatment zones.” The height of the individual treatment zones  160  is preferably 0.1 to 0.5 mm. The preferred width of the individual treatment zones  160  is 0.1 to 2.0 mm, and more preferably 0.5 to 1.0 mm. The depth of the needle penetration into the skin  150  is preferably 0.025 to 2.0 mm and more preferably from 0.2 to 1.0 mm. Preferably the needles  115  penetrate into the dermis or epidermis to directly heat dermal or epidermal tissue through resistive heating. Larger or smaller treatment zones are within the scope of the invention and the size and location of the treatment zones will be application specific. There are some applications, such as for example, tattoo removal or fat removal that treatment will extend down into the subcutaneous fat or deeper. The pulse conditions outlined here produce substantial lateral tightening of skin tissue and treat substantial portions of the dermal tissue. These parameters can be used to coagulate collagen within the skin and to kill or injure cells to stimulate the wound healing response in surrounding healthy tissue.  
         [0082]     Although the detailed description contains many specifics, these should not be construed as limiting the scope of the invention but merely as illustrating different examples and aspects of the invention. It should be appreciated that the scope of the invention includes other embodiments not discussed in detail above. For example, the disposable tip embodiment can also be used with needles that do not deliver a therapeutic substance. Various other modifications, changes and variations which will be apparent to those skilled in the art may be made in the arrangement, operation and details of the method and apparatus of the present invention disclosed herein without departing from the spirit and scope of the invention as defined in the appended claims. Therefore, the scope of the invention should be determined by the appended claims and their legal equivalents. Furthermore, no element, component or method step is intended to be dedicated to the public regardless of whether the element, component or method step is explicitly recited in the claims.  
         [0083]     In the claims, reference to an element in the singular is not intended to mean “one and only one” unless explicitly stated, but rather is meant to mean “one or more.” In addition, it is not necessary for a device or method to address every problem that is solvable by different embodiments of the invention in order to be encompassed by the claims.