Abstract:
A microneedle insertable in a target cell tissue, including a manipulative end maintained exterior of cell tissue and an insertion end positionable in or adjacent of target cell tissue. A plurality of microtubes are bundled to pass through the needle body and extend to respective distal ends grouped proximally interior of the insertion end. A sensing fiber is extendable from means for sensing for passage through the needle body to a distal end capable of sensing cell tissue parameters. The insertion end and the bundled microtube and sensing fiber distal ends are positionable in or adjacent of cell tissue thereby providing rapid evaluation of cell parameters by optic fiber sensing, fiber sampling of cell parameters, and precise delivery of therapeutic fluids or additional treatment measures. A method is also disclosed of precisely positioning a microneedle having a plurality of microtubes and sensing fibers therein for evaluating and treating cell tissue.

Description:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     The invention described herein may be manufactured, used and licensed by or for the Government for governmental purposes without the payment to the inventors and/or the assignee of any royalties thereon. 
    
    
     CROSS-REFERENCE TO RELATED APPLICATIONS 
     Not Applicable. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a micro-sized needle which is insertable through a patient&#39;s dermal layer for sampling of tissue in vivo. More specifically, the present invention relates to a needle having a micrometer internal diameter through which a plurality of sensing probes and delivery tubules are extended for monitoring cell parameters at the needle distal end and for delivering therapeutic fluids directly into tissue cells. 
     2. Description of the Related Art 
     Prior medical procedures for delivery of therapeutic fluids to treat systemic diseases include utilizing a hypodermic needle for delivery of mixtures of medication by means of an intravenous (IV) drip into a patient&#39;s vein. If the disease is diagnosed early and is localized in one organ or a group of cells within a patient, then systemic distribution of the medication within the patient by the arteries and veins is not efficient when compared to delivery of medication by hypodermic needle inserted proximal of the diseased cells. Typical hypodermic needles utilized in prior medical procedures include needles having an outer diameter (OD) of approximately 300 micrometers, and having an internal diameter (ID) of approximately 150 micrometers. One type of a medication infusion system is illustrated in U.S. Pat. No. 4,191,184 (the &#39;184 patent), issued to J. A. Carlisle. The infusion regulation system of the &#39;184 patent provides for regulating, monitoring, and control of IV infusion of fluids in a patient. The infusion regulation system provides a volume control apparatus including a peristaltic pump unit providing fluid flow through divaricated tubing for delivery of measured volumes of fluids to an outlet tube attached to a cannula inserted in a patient&#39;s vein. The system of the &#39;184 patent provides for systemic infusion of a relatively large volume of pre-mixed fluid and lacks the ability to deliver one or more therapeutic fluids in precise volumes to a tumor or numerous groups of diseased cells. 
     Prior medical procedures for positioning of probes by means of an incision into a patient includes insertion of optic fibers in a patient to view a tumor, or insertion of surgical instruments to excise a tumor. One example includes a surgical instrument inserted through a sleeve member positioned in an incision proximal of a joint member as illustrated in U.S. Pat. No. 4,461,281 (the &#39;281 patent), issued to R. W. Carson. The arthroscopic surgical apparatus of the &#39;281 patent includes a hollow cannula having an ID of about 5 mm for insertion therein of a blade shaped tip of an elongated shaft. The cannula provides a tubular guide to position the blade shaped tip in a knee joint and to facilitate penetration by the blade shaped tip through the subcutaneous tissue and fascia of the knee joint during joint tissue repair. Additional cutting tools or optic fibers are utilized by inserting through a second cannula positioned proximal of the knee joint and adjacent to first cannula, or the blade shaped tip of the elongated shaft is removed from first cannula followed by insertion of a second cutting tool or an optic fiber for viewing the joint tissue repair. The apparatus of the &#39;281 patent does not provide for one needle which remains positioned in an incision during a surgical procedure, with one needle having multiple channels therein for positioning of optic fibers for viewing while concurrently positioning one or more treatment instruments against the joint tissue undergoing repair. 
     Recent medical procedures utilizing probes inserted into a patient&#39;s organs includes positioning of laser probes for eye surgery as illustrated in U.S. Pat. No. 5,643,250 (the &#39;250 patent), issued to F. E. O&#39;Donnell, Jr., and in U.S. Pat. No. 6,520,955 (the &#39;955 patent), issued to M. Reynard. The &#39;250 patent illustrates a laser probe which includes a fiber optic channel and an infusion port for irrigating solutions to be infused into an eye during laser surgery on cornea tissue. The laser probe is manipulated as a hand piece for insertion of the probe tip through the cornea of a patient&#39;s eye, in order to position the probe tip having a fiber optic opening therein in close proximity to the target cataract tissue. The laser probe diameter may not allow insertion through numerous layers and densities of tissues disposed between a dermal surface and internal organs disposed medially within a patient. The &#39;955 patent illustrates a process and apparatus for removing cataract tissue in an eye and for injecting a lens replacement material into the eye lens to fill the intralenticular space. The apparatus of the &#39;955 patent includes a needle having dual cannula oriented as coaxial annular conduits through which chemicals and enzymes are delivered into cataract tissue. A separate focused laser is utilized to destroy the cataract tissue, followed by destroyed cataract tissue being removed by aspiration through an aspiration instrument or through a coaxial annular conduit of the needle. The diameter and configuration of the dual cannula needle may limit precise insertion into a specific tumor in an organ after needle insertion through multiple layers and tissue densities within the patient. 
     A need exists for a minimally intrusive microneedle which is positionable into a cell or a group of cells, and is capable of actively retrieving samples for monitoring of current cell conditions while remaining inserted in the cell or group of cells. There is a further need for a microneedle having a plurality of microtubules providing channels for optic fibers, channels for samples intracellular conditions, and channels for delivery of therapeutic fluids into the cell in order to promote healing of, or selective suppression of specific cells. 
     BRIEF SUMMARY OF THE INVENTION 
     A microneedle is disclosed for insertion in a patient without significantly disrupting overlying tissue layers in order to precisely position an insertion end adjacent to a target cell mass or to position the insertion end in a target cell tissue. The microneedle includes a manipulative end maintained exterior of the target cell tissue, with the manipulative end in fluid communication with means for fluid flow and at least one fluid flow source, and/or in optical or electrical communication with a cell parameter monitoring source and one or more therapeutic treatment sources. The microneedle insertion end includes a tapered length having a diminishing outer diameter to allow positioning in or adjacent to the target cell tissue. A needle body joins the manipulative and insertion ends. 
     The microneedle includes one or a plurality of microtubes disposed in a bundled configuration within the needle body. The microtubes have distal ends grouped proximal to and interior of the microneedle insertion end. The plurality of microtubes include at least one fluid flow microtube extending to a distal end disposed proximal of the microneedle insertion end, thereby allowing repetitive delivery of a primary treatment fluid into, or removal of cell fluids from the target cell tissue. A second fluid flow microtube is readily incorporated within the plurality of microtubes, with the second fluid flow microtube extending to a second flow end disposed at the microneedle insertion end, thereby allowing repetitive delivery of secondary treatment fluid into or removal of cell fluids treated with the primary treatment fluid delivered by the first fluid flow microtube. Each fluid flow microtube is coupled with the means for fluid flow source such as a microfluidic pump capable of fluid delivery rates of about five microliters/minute. 
     The microneedle further includes one or more sensing fibers extended within the microneedle body, with one sensing fiber having an optic fiber end disposed at the microneedle insertion end, and an optical detector and transmission fiber extending from the microneedle insertion end and extending to the microneedle manipulative end. Additional sensing fibers extending through the microneedle body can include a pH sensing fiber having a pH assay end at the microneedle insertion end, a thermal fiber having a heat transfer end at the microneedle insertion end positionable within or adjacent to the target cell tissue. Another embodiment of the microneedle includes an oxygen sensor fiber extended through the microneedle body, with an oxygen sensor end at the microneedle insertion end, and/or a temperature sensing fiber extended through the microneedle body, with a temperature sensor end at the microneedle insertion end. Further embodiments of the microneedle include a vibration fiber extended to a vibratory end at the microneedle insertion end. 
     Implementation of the microneedle includes the insertion end being positioned within or adjacent to the target cell tissue, thereby positioning the plurality of microtubes distal ends and associated sensing fibers and fluid flow microtubes within the target cell tissue or adjacent to the target tissue mass. The sensing fibers provide evaluation of the cell tissue internal conditions while the fluid flow microtubes provide flow paths for delivery of one or more treatment fluids to the target cell tissue, thereby adjusting the cell tissue internal conditions to preferred levels of pH, oxygen content, temperature, and osmotic balance to facilitate healing of diseased and/or damaged cell tissue. Upon the advice by medical personnel after monitoring of the cell tissue internal conditions with the microneedle, an exact dose of therapeutic medicine, oxygen, vibration, and/or thermal transfer is dispensed through the microneedle, with resulting promotion of cellular healing or poisoning of malignant cells. The microneedle is readily removed and discarded, or reused after sterilization. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention is illustrated in the drawings in which like element numbers represent like parts in each figure, including: 
         FIG. 1  is a side view of one embodiment of the present invention, illustrating a microneedle having a manipulative end connected with means for fluid flow, a cell parameter monitoring source, and one or more therapeutic treatment sources; 
         FIG. 2  is a perspective view of the microneedle of  FIG. 1 , illustrating a needle body in which a plurality of microtubes extend to a microneedle insertion end; 
         FIG. 3A  is a side perspective view of the microneedle insertion end having a plurality of microtube distal ends disposed therein; 
         FIG. 3B  is a side view of  FIG. 3A , illustrating and internal diameter of the insertion end from which a staggered grouping of microtube distal ends extend; 
         FIG. 4  is a side view of an optical fiber and detector in communication with one of the plurality of microtubes illustrated in  FIG. 2 ; 
         FIG. 5  is a schematic diagram of means for fluid flow including flow pump and fluid source in communication with at least one microtube as illustrated in  FIG. 2 ; 
         FIG. 6A  is a cross-sectional view of a human female breast in which the microneedle insertion end is positioned in target cell tissue into which a plurality of microtubes and/or microfibers distal ends extend; 
         FIG. 6B  is an exploded view of a manipulative end of the microneedle of  FIG. 6A , from which a plurality of microtubes and/or microfibers proximal ends extend; 
         FIG. 7A  is a cross-sectional view of a human male reproductive system in which the microneedle insertion end is positioned in target cell tissue into which a plurality of microtubes and/or microfibers distal ends extend; 
         FIG. 7B  is an exploded view of a manipulative end of the microneedle of  FIG. 7A , from which a plurality of microtubes and/or microfibers proximal ends extend; 
         FIG. 8A  is a cross-sectional view of a human knee joint in which the microneedle insertion end is positioned adjacent to torn tissue into which a plurality of microtubes and/or microfibers distal ends extend; and 
         FIG. 8B  is an exploded view of a manipulative end of the microneedle of  FIG. 8A , from which a plurality of microtubes and/or microfibers proximal ends extend. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring now to  FIGS. 1-8B , a multiple channel needle and delivery system  10  is disclosed, including a microneedle  20  sized for insertion into cell tissue within a patient without significantly disrupting a patient&#39;s dermal surface  12  or underlying tissue layers proximal of a target cell tissue  14  or a target tumor mass  16 . The microneedle  20  includes a distal insertion end  24  having an elongated and tapered end opening  26  (see  FIGS. 2 ,  3 A and  3 B), thereby readily allowing positioning of the insertion end  24  and end opening  26  within the target cell tissue  14 , a tumor mass  16 , or an internal organ or joint (see  FIGS. 6-8B ). The microneedle  20  includes a proximal end, identified herein as a manipulative end  28 , which is maintained exterior of the target cell tissue  14  during positioning of the insertion end  24 . The manipulative end  28  is sized in internal diameter (ID) to receive therein one or more microtubes  48 ,  48 ′, and/or one or more microfibers  30 ′,  32 ′,  34 ′,  36 ′. The manipulative end  28  can be coupled with a stopper or spacer  22  inserted therein and having an insertion end  22 ′ and a proximal end  22 ″, serving as a block from exiting of tissue fluids from the manipulative end  28 , and serving to maintain grouping of the plurality of microtubes and microfibers within the microneedle  20  during insertion through the patient&#39;s tissue layers and during positioning at the target cell tissue  14 . 
     The microtube  48 ,  48 ′ proximal ends are extended outwards from the manipulative end  28  for a sufficient distance to connect with means for fluid flow including a micropump  40  and at least one fluid flow source, thereby maintaining fluid communication between the micropump  40  and fluid flow source and at least one fluid flow microtube  48 ,  48 ′ extended through a needle body interior  28 ′. The needle body includes a cross-section having a cylindrical, oval or multi-sided cross-section, extends a sufficient length to join the manipulative end  28  and insertion end  24 . The main portion of the needle body  20  includes an OD  20 ″ of up to about 150 micrometers (hereinafter, microns), and an ID  28 ″ of up to about 120 microns. Additional embodiments for the main portion of the needle body  20  provide an alternative OD  20 ″ of between about 80 microns to about 120 microns, and an alternative ID  28 ″ of between about 70 microns to about 110 microns. The distal insertion end  24  forms an elongated and tapered end opening  26  with a cross-sectional dimension diminishing from about 110 microns to a distal end a cross-sectional dimension of about 70 microns. The needle body  20  is manufactured of a biocompatible material known to those skilled in the art, such as heat-treatable stainless steel, carbon steel, or carbon based materials. 
     The microneedle manipulative end  28  includes a sufficient ID  28 ″ to retain therein one or more microtubes  48 ,  48 ′, and/or one or more microfibers  30 ′,  32 ′,  34 ′,  36 ′ grouped in a space efficient bundled configuration within the needle body  20 . Each microfiber includes an outer diameter of between about 40 microns to about 50 microns. Each microfiber includes a proximal end extended from the manipulative end  28  for connection with one or more means for sensing, such as one or more sensing devices including, but not limited to, a light source  30  and photodetector  34 , and/or monitoring devices for assessing pH, oxygen content, temperature, and osmotic balance within the target cell tissue  14 . Each respective microfiber is composed of a biocompatible material chosen by those skilled in the art to facilitate the function of each microfiber (i.e. optical transmission, detecting of pH, oxygen, etc.). The bundled configuration includes any combination of a microtube and a microfiber, or multiple microtubes and multiple microfibers in bundled combinations of three, five, seven, and up to nineteen combined microtubes and microfibers extended through the needle body interior  28 ′ length. Each microtube and microfiber includes distal ends extended proximally of the interior surface  28 ′″ of the insertion end  24  (see  FIG. 2 ). One configuration for the distal ends is illustrated in  FIGS. 3A and 3B , whereas one or more of microtubes and/or microfibers have distal ends extended outwards from the elongated and tapered end opening  26  of the insertion end  24  in order to facilitate interaction between the distal ends and the target cell tissue  14 . In one embodiment, the multiple microtubes extended through the microneedle  20  include at least one fluid flow microtube  48  in fluid connection with the means for fluid flow, such as a micropump and fluid flow source. A second fluid flow microtube  48 ′ is readily incorporated in the plurality of microtubes, with the second fluid flow microtube  48 ′ extending to a second distal flow end disposed at the insertion end  24 , thereby allowing constant or intermittent delivery of secondary treatment fluid into or removal of cell fluids from the target cell tissue  14  in coordination with the primary treatment fluid delivered by fluid flow microtube  48 . The microtubes include an inside diameter of between about 50 microns to about 90 microns, with a smaller ID preferred when five or more microtubes are bundled within the needle body  20 . The microtubes  48 ,  48 ′ are manufactured of a biocompatible material known to those skilled in the art, such as heat-treatable stainless steel, carbon steel, or carbon based materials. 
     The fluid flow source can include a pulsatile micropump  40  and micromixer known to those skilled in the art (see  FIG. 5 ). The pump rate of the micropump  40  is readily adjustable by an operator of the microneedle  20  and by means of input to a microprocessor (MP)  50  (see  FIG. 1 ), having a communication path  52  with micropump  40 , and having communication paths  52 ′,  52 ″ with photodetectors  34 ,  36  of the delivery system  10 , to provide a typical flow rate in a range of between about 1.5 microliters/minute to about five microliters/minute of a primary treatment fluid and/or second treatment fluid through the distal end of the fluid flow microtube  48  for delivery to the target cell tissue  14  or target tumor mass  16 . As illustrated in  FIG. 5 , a pulsatile micropump  40  includes two inlet chambers  42 ,  42 ′, each of about 800 microns in diameter, in which a bubble is created by polysilicon resistors on quartz which act as heaters in each chamber  42 ,  42 ′. Each bubble created serves as a micropiston to drive fluid from each chamber  42 ,  42 ′ and into and through respective microchannels  44 ,  44 ′. The fluid flows through check valves  46 ,  46 ′ which direct fluid flow movement from the inlet chambers  42 ,  42 ′ to the output portion of the micropump  40 , thereby directing fluid flow  20 ′ into and through one or more microtubes  48 ,  48 ′ extended through the microneedle  20  to the insertion end  24 . 
     The embodiments illustrated in  FIGS. 2-3B  include at least a first optical fiber  30 ′ connected with a light source  30  positioned external of the patient. The first optical fiber  30 ′ extends the interior length of the microneedle  20  to an optic fiber end disposed at the insertion end  24 . Paired with the first optical fiber  30 ′ is an optical detector fiber  34 ′ extending from the optic fiber end, through the microneedle  20 , and connected with a photodetector  34  (see  FIGS. 1 and 4 ). In order to increase the optical viewing ability of the microneedle  20 , a second optical fiber  32 ′ can be included and connected with a second light source  32  positioned external of the patient. The second optical fiber  32 ′ also extends the interior length of the microneedle  20  to a second optic fiber end (see  FIGS. 3A and 3B ), which is disposed at the insertion end  24 . Paired with the second optical fiber  32 ′ is a second optical detector fiber  36 ′ extending from the optic fiber end  38 , through the microneedle  20 , and connected with a second photodetector  36  (see  FIG. 1 ). 
     The plurality of microtubes and/or microfibers bundled within the microneedle  20  further includes an option for a pH sensing fiber to be retractably extended through the needle body interior  28 ′ in order to position a pH assay distal end  38  at the insertion end  24  (see  FIG. 3B ). The pH sensing fiber can be configured as an optical fiber having a pH sensitive film or dye disposed on the distal end  38  (see  FIG. 4 ), or configured as an electrical conductive fiber having a distal end sensitive to ionic concentration changes indicative of the pH within a target cell  14  or tumor mass  16 . The optical fiber and pH sensing fiber configuration allows for optical signals to be continually or intermittently transmitted through the optical fiber until changes in the optical properties of the pH sensitive film or dye on the distal end is detected by detector  34 , thereby indicating a pH change in the target cell  14  or tumor mass  16 . 
     Additional embodiments for the plurality of microtubes and/or microfibers include a thermal fiber extended through the needle body interior  28 ′, and having a heat transfer end positioned distally from the insertion end  24  to provide heat exchange within or adjacent to the target cell  14  or tumor mass  16 . Also, an oxygen sensor fiber  58  can be extended through the needle body interior  28 ′, with an oxygen sensor end extended from the insertion end  24 . In addition, a vibratory fiber  54  can be through the needle body interior  28 ′, with a vibratory distal end positioned distally from the insertion end  24  (see  FIG. 3B ). The vibratory distal end can be activated to provide internal vibration within the target cell  14  or tumor mass  16 , to provide therapy or to selectively destroy the target tissue(s) without chemotherapy. 
     A method of precisely positioning a microneedle having a plurality of microtubes and sensing fibers therein for evaluating and treating target cell tissue is also disclosed. Implementation of the microneedle includes the insertion end being positioned within or adjacent to the target cell tissue, thereby positioning the plurality of microtubes distal ends and associated sensing fibers and fluid flow microtubes within the target cell tissue or adjacent to the target tissue mass. The sensing fibers provide evaluation of the cell tissue parameters by medical personnel, including optically viewing the cell tissue, and/or sensing the pH, oxygen content, temperature, or other significant cell parameters. The fluid flow microtubes provide flow paths for delivery of one or more treatment fluids to the target cell tissue, thereby adjusting the cell tissue internal conditions to preferred levels of pH, oxygen content, temperature, and/or osmotic balance to facilitate healing of diseased and/or damaged cell tissue. Upon the advice by medical personnel after monitoring of the cell tissue parameters with the microneedle, an exact dose of therapeutic medicine, oxygen, vibration, and/or thermal transfer is readily delivered through one or more of the microtubes of the microneedle, with resulting promotion of cellular healing or poisoning of malignant cells. The microneedle is readily removed and discarded, or reused after sterilization. 
     A multitude of applications are readily apparent to one skilled in the medical arts, including positioning of the microneedle in target cell tissue residing in any living organ which is not moving or has been stopped or slowed in movement. An example of one of many applications is illustrated in  FIGS. 6A and 6B  for inserting a microneedle  20  in order to assess and treat targeted cell tissue  14  in a human female breast  60 . Another example of an application is illustrated in  FIGS. 7A and 7B  for inserting a microneedle  20  in order to assess and treat targeted cell tissue  14  in a human male reproductive system  70 . The needle  20  in  FIGS. 7A and 7B  illustrates a needle body including a buckle or bend  20 ′″ engineered and manufactured therein, to facilitate manipulation of the needle body and microtubes therein through a natural orifice and interior channels of a patient during needle into a patient. An additional application is illustrated in  FIGS. 8A and 8B  for inserting a microneedle  20  adjacent to a site of torn tissue  82  in a human knee joint  80 , in order to assess, repair and/or remove the tissue  82 . Further applications for the microneedle  20  include insertion in a shoulder, hip joint, or back vertebrae for repair of torn tissue or for treatment of calcified tissue. The described applications for a multiple channel needle and delivery system  10  are not intended to be all-inclusive, nor limiting to additional applications in humans and applications in mammals. 
     While numerous embodiments and methods of use for this invention are illustrated and disclosed herein, it will be recognized that various modifications and embodiments of the invention may be employed without departing from the spirit and scope of the invention as set forth in the appended claims. Further, the disclosed invention is intended to cover all modifications and alternate methods falling within the spirit and scope of the invention as set forth in the appended claims.