Abstract:
The determination of analyte concentration in physiological samples is of ever increasing importance to today&#39;s society. Such assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in the diagnosis and management of a variety of disease conditions. In the present application, a method is described which may be used for the manufacture of medical devices which include an integrated lancet and sensor.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     The present invention relates, in general, to medical devices containing an integrated lancet and sensor and, more particularly, to a process for manufacturing the medical devices.  
         [0002]     The determination of analyte concentration in physiological samples is of ever increasing importance to today&#39;s society. Such assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in the diagnosis and management of a variety of disease conditions. Analytes of interest include glucose for diabetes management, cholesterol for monitoring cardiovascular conditions, drugs for monitoring levels of therapeutic agents, and identifying illegal levels of drugs, and the like. In response to this growing importance of analyte concentration determination, a variety of analyte concentration determination protocols and devices for both clinical and home testing have been developed.  
         [0003]     In determining the concentration of an analyte in a physiological sample, a physiological sample must first be obtained. Obtaining and testing the sample often involves cumbersome and complicated procedures. Unfortunately, successful manipulation and handling of test elements, such as test strips, lancing members, meters and the like is to a great extent dependent on the visual acuity and manual dexterity of the user, which in the case of people with diabetes is subject to deterioration over the course of the disease state. In extreme cases people that have significant loss of sight and sensation, testing procedures can become significantly difficult and require additional assistance from ancillary devices or personnel.  
         [0004]     A typical procedure for making a glucose measurement with the use of a test strip involves the following actions or steps (but not necessarily in the order given): (1) removing supplies from a carrying case, (2) removing a lancing device loading cap or door, (3) removing and disposing of a used lancet from the lancing device, (4) inserting the lancet in the lancing device, (5) twisting off a protective cap from the lancet, (6) replacing the lancing device cap, (7) cocking the lancing device, (8) opening a test strip vial/container, (9) removing a strip from the container and inserting or interfacing it with a meter, (10) holding a lancing device to the skin, (11) firing the lancing device, (12) removing the lancing device from the skin, (13) extracting a sample, (14) applying sample to the test strip and obtaining results of the measurement; (15) disposing of the test strip, (16) cleaning the test site, and (17) returning supplies to the carrying case. Of course, certain glucose measurement systems and protocols may involve fewer or more steps.  
         [0005]     One manner of reducing the number of actions is by the use of integrated medical devices that combine multiple functions in order to minimize the handling of sensor and/or lancing components that may lead to contamination of the components and/or injury to the user. An example of such an integrated medical device that includes a test strip and lancet is described in International Application No. PCT/GB01/05634 (published as WO 02/49507 on Jun. 27, 2002) and U.S. patent application Ser. No. 10/143,399, both of which are fully incorporated herein by reference.  
         [0006]     Technological advancements have been made in test strip fabrication in which both sensor and lancing functions and the structures to provide such functions are provided on a single fully integrated medical device, as described in the aforementioned U.S. patent application Ser. No. 10/143,399. Integrated medical devices are typically in the form of strips. Web-based methods can be used to make such fully integrated medical devices which are singulated after fabrication prior to being collectively packaged in a cartridge, magazine, cassette or the like. Examples of web-based methods for making such medical devices are disclosed in U.S. patent application Ser. No. 10/142,409 and European Patent Application EP 1360932 A1, both of which are fully incorporated herein by reference. These web-based methods, however, require expensive equipment that requires substantial manufacturing floor space. In web-based methods, the alignment of the sensor and lance can also change during the manufacturing process. The sensor and lance must, however, be precisely aligned to ensure proper function of the integrated medical device.  
         [0007]     Still needed in the field, therefore, is an inexpensive and simple method of fabricating an integrated medical device containing a lancet and a test strip. This method should also produce integrated medical devices in which the sensor and lance are precisely aligned.  
       SUMMARY OF THE INVENTION  
       [0008]     In one embodiment of the present invention a method of assembling integrated medical devices includes the steps of providing a medical device assembly apparatus including a body having a proximal end, and a distal end, a detachable clamping bar, and a pusher plate. In this embodiment of the present invention, the proximal end of the assembly apparatus includes a plurality of recesses for receiving and removably retaining a plurality of test strips at least partially therein. In this embodiment of the invention, the method includes loading a test strip containing a top layer of heat-seal adhesive into each recess, placing a plurality of dermal tissue penetration members on top of the test strips, securing the plurality of dermal tissue penetration members with the clamping bar to minimize movement, urging the test strips into alignment with the dermal tissue penetration members using the pusher plate, heating the dermal tissue penetration members to a predetermined temperature to adhere the strips to the dermal tissue penetration members and removing the medical devices from the assembly apparatus for further processing. In the method of one embodiment of the present invention, heat is applied evenly across the dermal tissue penetration members to ensure complete adhesion between the strips and the dermal tissue penetration members. In one embodiment of the method according to the present invention, the dermal tissue penetration members are connected by a bandolier. In one embodiment of the method according to the present invention, the predetermined temperature is between 95° C. and 150° C.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]     A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (wherein like numerals represent like elements), of which:  
         [0010]      FIG. 1  is an exploded perspective view of an integrated medical device assembly apparatus according to an embodiment of the present invention;  
         [0011]      FIGS. 2A and 2B  are perspective and side views, respectively, of a medical device that can be used with exemplary embodiments of the assembly apparatus according to the present invention;  
         [0012]      FIGS. 3A and 3B  are cross-sectional side views of a portion of the medical device assembly apparatus of  FIG. 1B  along A-A′ in the direction of the arrows, representing exemplary embodiments of assembly apparatus recesses.  
         [0013]      FIGS. 4A and 4B  are perspective and exploded perspective views, respectively, of an integrated medical device assembly apparatus according to another exemplary embodiment of the present invention;  
         [0014]      FIG. 5  is a flow chart illustrating a sequence of steps in a process for manufacturing an integrated medical device using the assembly apparatuses according to exemplary embodiments of the present invention;  
         [0015]      FIGS. 6A-6H  are schematic, perspective views depicting stages of a process for manufacturing medical devices according to present invention; and  
         [0016]      FIGS. 7A-7I  are schematic perspective views depicting stages of a process for manufacturing medical devices according to the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0017]      FIG. 1  is an exploded perspective view of a medical device assembly apparatus  100  according to an exemplary embodiment of the present invention. Assembly apparatus  100  includes a body  102 , a detachable clamping bar  103  with a plurality of locating pins  104 , and a detachable test strip pusher plate  106  with a plurality of spring-loaded protrusions  107 . Assembly apparatus  100  is generally rectangular in shape and can be formed of metal or any material that can withstand a temperature ranging from about 95° C. to 150° C.  
         [0018]      FIGS. 2A and 2B  are perspective and side views, respectively, of an exemplary integrated medical device  200  that can be manufactured using assembly apparatus  100  according to one aspect of the present invention. Integrated medical device  200  includes a test strip  204  and a dermal tissue penetration member  202 . Test strip  204  has a reaction area  205  and electrical contacts  206  that terminate on a proximal end  210  of integrated medical device  200 . Electrical contacts  206  are made of any suitable conductive material, such as gold, silver, platinum or carbon. Dermal tissue penetration member  202  includes a lancet  220  adapted to pierce a user&#39;s skin and draw blood into reaction area  205 . Dermal tissue penetration member  202  is adhered to test strip  204  by an adhesive layer  214 . This adhesive layer  214  can be heat seal or pressure sensitive adhesive. Lancet  220  includes a lancet base  222  that terminates at the distal end  212  of the assembled test strip. Further descriptions of integrated medical devices that can be manufactured using assembly apparatus  100  according to the present invention are in the aforementioned International Application No. PCT/GB01/05634 and U.S. patent application Ser. No. 10/143,399. In addition, dermal tissue penetration member  202  can be fabricated, for example, by a progressive die-stamping technique, as disclosed in the aforementioned International Application No. PCT/GB01/05634 and U.S. patent application Ser. No. 10/143,399.  
         [0019]     Referring again to  FIG. 1 , body  102  of assembly apparatus  100  includes a first side  108 , a second side  110 , a first end  112 , a second end  114 , an upper surface  116  and a lower surface  118 . At first side  108  is a plurality of protrusion guides  119  which may be, for example hollow, tubular-shaped for the plurality of protrusions  107  to move through. The function of protrusions  107  is to move through protrusion guides  119  thereby pushing strips positioned in recess  120  into alignment with dermal tissue penetration members  202  during the manufacturing process, as will be described in more detail below (see  FIGS. 5 and 6 E). The cross section of protrusion guides  119  are shaped to accommodate the cross-sectional shape of protrusions  107 .  
         [0020]     Adjacent to protrusion guides  119  is a plurality of recesses  120  and groove  122  which may be, for example elongate in shape on upper surface  116  running from first end  112  to second end  114  (i.e., in the X direction of  FIG. 1 ) substantially parallel to first side  108 . Adjacent to groove  122  are a plurality of locating pin receiving holes  126 . The function of locating pin holes  126  is to align and secure clamping bar  103  through locating pins  104  to body upper surface  116 , as will be described in more detail below (see  FIGS. 5, 6C  and  6 D).  
         [0021]     Recesses  120  each contain at least one recess wall  129  approximately perpendicular to groove  122  (i.e., in the Y direction, see  FIG. 1 ). Recess  120  is configured (e.g., sized, shaped and/or orientated) to receive and to removably retain a test strip  204  (illustrated in  FIGS. 2A and 2B  as part of integrated medical device  200 ) at least partially therein. The number of recesses  120  can range from 10 to 100 and more usually ranges from 20 to 50. The width of recess  120  (i.e., in the X direction) is marginally larger (e.g., about 1-3%) than the width of test strip  204  such that test strip  204  fits snugly therein. This snug fit beneficially minimizes side-to-side movement of the strip during the integrated medical device assembly process (see  FIG. 5 ) such that alignment between test strip  204  and dermal tissue penetration member  202  in the X direction is maintained.  
         [0022]     Recesses  120  can be formed by processes known to those skilled in the art including, but not limited to, spark erosion and electrical discharge machining (EDM). Types of EDM include, for example, wire, sinker and small hole EDM. Cross-sectional side views of recess  120  are shown in  FIGS. 3A and 3B . Recess  120  includes at least one rounded inner corner  130  bounded by recess wall  129  and a recess base surface  131 . An exemplary embodiment of recess  120  is shown in cross-section in  FIG. 3A . In this embodiment, test strip  204  within recess  120  contacts a region on corner  130  but does not contact recess base surface  131 . In other words, test strip  204  is held remote from recess base surface  131  by corner  130  which may be, for example a rounded inner corner.  FIG. 3B  illustrates another exemplary embodiment of recess  120  in which corners  130  are wire eroded to form a depression of approximate semi-circular cross section bounded by recess wall  129  and recess base surface  131  to allow test strip  204  to lie flat within recess  120 . This beneficially allows close contact of test strip  204  with recess base surface  131 , ensuring complete and even adhesion between test strip  204  and dermal tissue penetration member  202  during the heat seal step in process  500  (see  FIGS. 5, 6F  and  6 G).  
         [0023]      FIGS. 4A and 4B  are perspective and exploded perspective views, respectively, of a medical device assembly apparatus  400  according to another exemplary embodiment of the present invention. Assembly apparatus  400  includes a body  402 , a detachable clamping bar  403  with a central locating pin  404 , two outer locating pins  405  and a detachable spring-loaded test strip pusher plate  406 . Assembly apparatus  400  is generally rectangular in shape and can be formed of metal or any material that can withstand a temperature ranging from about 95° C. to 150° C.  
         [0024]     Assembly apparatus body  402  includes a first side  408 , a second side  410 , a first end  412 , a second end  414 , an upper surface  416  and a lower surface  418 . Second side  410  can include a stepped shape for securing assembly apparatus  400  in a heat-sealing apparatus prior to the integrated medical device assembly process. Adjacent to first side  408  is an elongate recess-containing member  420  and groove  422  on upper surface  416  running from first end  412  to second end  414  (i.e., in the X direction, see  FIGS. 4A and 4B ) substantially parallel to recess-containing member  420 . Adjacent to groove  422  are outer locating pin slots  424  near to each of first and second ends  412  and  414 . Also adjacent to groove  422  in substantially the center of body  402  is a central locating pin receiving hole  426 . The function of outer locating pin slots  424  and central locating pin receiving hole  426  is to align and secure clamping bar  403  through central locating pin  404  and outer locating pin  405  to body upper surface  416 , as will be described in more detail below (see  FIGS. 5, 7E  and  7 F).  
         [0025]     Recess-containing member  420  includes a plurality of recesses  428  each containing at least one recess wall  429  approximately perpendicular to groove  422  (i.e., in the Y direction, see  FIGS. 4A and 4B ). Recess  428  is configured (e.g., sized, shaped and/or orientated) to receive and to removably retain a test strip  204  (illustrated in  FIGS. 2A and 2B  as part of integrated medical device  200 ) at least partially therein. The number of recesses  428  can range from 10 to 100 and more and usually ranges from 20 to 50. The width of recess  428  (i.e., in the X direction) is marginally larger (e.g., about 1-3%) than the width of test strip  204  such that test strip  204  fits snugly therein. This snug fit beneficially minimizes side-to-side movement of the strip during the integrated medical device assembly process (see  FIG. 5 ) such that alignment between test strip  204  and dermal tissue penetration member  202  in the X direction is maintained.  
         [0026]     Recess-containing member  420  is securely attached to body  402  by means or processes known to those skilled in the art including, for example, bolting, dowelling and welding. Recess-containing member  420  is fabricated separately from body  402  so that recesses  428  can be formed by processes known to those skilled in the art including, but not limited to, spark erosion and electrical discharge machining (EDM). Types of EDM include, for example, wire, sinker and small hole EDM. The exemplary embodiments of recess  428  shown in  FIGS. 3A and 3B  can also be used in assembly apparatus  400 .  
         [0027]     Referring again to  FIGS. 4A and 4B , pusher plate  406  includes a plate proximal side  432  facing recess-containing member  420 , a plate distal side  434 , a first end  436  and a second end  438 . Plate proximal side  432  includes a resiliently deformable band  440  along the entire length of plate  406  from first end  436  to second end  438  and extending to approximately half the height and width of pusher plate  406 . Deformable band  440  contacts test strips  204  as pusher plate  406  is urged against recess-containing member  420 , as will be described below (see  FIGS. 5 and 7 G).  
         [0028]     Deformable band  440  can be formed of any resiliently deformable material known to those skilled in the art including, but not limited to, Styrofoam materials, elastomeric materials, silicone materials, latex materials, polymeric materials, polyurethane materials and any combination thereof. Deformable band  440  is detachably adhered to pusher plate  406  with semi-permanent adhesive to allow for removal when deformable band  440  is no longer functional, is soiled or is damaged. Any suitable adhesive known to those skilled in the art can be employed for this purpose including, but not limited to, pressure sensitive adhesives, cold-seal adhesives, heat-seal adhesives and releasable adhesives available from, for example, 3M, Basic Adhesives and Avery Dennison.  
         [0029]     Referring to  FIG. 4B , pusher plate  406  further includes at least one outer screw  442  with a spring  444  in surrounding relation to outer screw threads  445  and at least one inner screw  446 . A non-threaded outer screw plate hole  450  allows movement of pusher plate  406  relative to outer screw  442 . Outer screw  442  is anchored in recess-containing member  420  through an outer screw threaded body hole  452  that is aligned with non-threaded screw plate hole  450 . Inner screws  446  can move through the width of pusher plate  406  by threaded inner through screw hole  448 . Outer screw(s)  442  and inner screw(s)  446  are positioned inward from plate first end  436  and second end  438  approximately one quarter and one third of the length, respectively, of pusher plate  406  running in the X direction. Outer screw  442  and inner screw  446  are also positioned in pusher plate  406  below deformable band  440  such that movement of pusher plate  406  with respect to recess-containing member  420  on outer screw  442  and inner screw  446  is not impeded by deformable band  440 . Outer screw threaded body holes  452  are also included in recess-containing member  420  for receiving outer screws  442 . Outer screws  442  are screwed into recess-containing member  420  through outer screw threaded body holes  452  to a depth sufficient to allow movement of plate pusher  406  away from recess-containing member  420  and to allow compression of springs  444 . Inner screws  446  can touch but do not penetrate recess-containing member  420 .  
         [0030]      FIG. 5  is a flow chart illustrating a sequence of steps in a process  500  for manufacturing a plurality of integrated medical devices according to an exemplary embodiment of the present invention. Process  500  is described below utilizing  FIGS. 6A-6I  and  7 A- 7 I (schematic, perspective views depicting various stages of process  500 ). Process  500  will first be described utilizing assembly apparatus  100  shown in  FIGS. 6A-6I  and then will be described utilizing assembly apparatus  400  shown in  FIGS. 7A-7I .  
         [0031]     Process  500  includes first providing an assembly apparatus  100 , as set forth in step  510  of  FIG. 5  (see  FIG. 1 ). The provided assembly apparatus  100  includes a body  102 , a clamping bar  103  with a plurality of locating pins  104 , and a pusher plate  106  with a plurality of protrusions  107  which may be, for example, spring-loaded. Body  102  further includes a first side with a plurality of hollow protrusion guides  119  for the protrusions  107  to move therethrough. Adjacent to protrusion guides  119  is a plurality of recesses  120  configured to receive and to removably retain test strips  204  at least partially therein.  
         [0032]     Next, as set forth in step  520 , a previously fabricated test strip  204  with an exposed upper heat seal adhesive layer is placed in each recess  120  in assembly apparatus  100  (see  FIG. 6A ). Test strips  204  used in this process can be manufactured, for example, by web processes as disclosed in U.S. patent application Ser. Nos. 10/143,999 and 10/142,409 or by screen printing processes as disclosed in International Application No. PCT/GB03/04656 (DDI-5019 PCT; filed on Oct. 30, 2003).  
         [0033]     As set forth in step  530 , a set of 10 to 50 dermal tissue penetration members  202  attached to a common bandolier  154  through tabs  156  is next placed on top of test strips  204  in assembly apparatus  100  such that at least one bandolier hole  158  is aligned with at least one locating pin receiving hole  126  (see  FIGS. 6B-6C ).  
         [0034]     Subsequently, clamping bar  103  is attached to body upper surface  116  by placing locating pins  104  through bandolier holes  158  and locating pin receiving holes  126 , thereby securing bandolier  154  (see  FIG. 6D ), as set forth in step  540 . Locating pins  104  beneficially securely hold bandolier  154  in place to ensure that there is minimal movement of dermal tissue penetration members  202  in the X, Y and Z directions during step  560  (see below).  
         [0035]     As set forth in step  550 , pusher plate  106  is urged toward body  102 , causing test strips  204  to be pushed toward body  102  in the Y direction by protrusions  107  (not shown). Protrusions  107  continue to push test strips  204  until the reaction areas on test strips  204  are aligned with a lancet base  222  (see  FIG. 6E ; strips and lancet base not shown). Movement of protrusions  107  in the Y direction is optionally guided by protrusion guides  119 . Protrusions  107  are spring loaded to accommodate variations in test strip length while ensuring that the strips are fully pushed against lancet base  222 .  
         [0036]     Next, assembly apparatus  100  is placed in a heat sealing apparatus and dermal tissue penetration members  202  are adhered to test strips  204  by a heat sealer  160 , as set forth in step  560  (see  FIGS. 6F-6G ). Any heat sealer known to those skilled in the art can be used in this step. Heat sealer  160  seals 2 to 20 medical devices at a time and more usually seals 5 to 10 at one time. Typical temperature, pressure and dwell times (i.e., time that the heat sealer contacts the dermal tissue penetration member) for heat sealer  160  range from 95-150° C., 15-40 N per lancet, and 1-5 seconds, respectively. The assembled integrated medical devices  200  attached to bandolier  154  (see  FIG. 6H ) are then removed from assembly apparatus  100  for further processing, i.e. for singulation by cutting through tabs  156  that connect dermal tissue penetration member  202  to the bandolier  154 .  
         [0037]     When assembly apparatus  400  is used in process  500 , process  500  includes first providing an assembly apparatus  400 , as set forth in step  510  of  FIG. 5  (see  FIG. 7A ). The provided assembly apparatus includes a body  402 , a clamping bar  403  with a central locating pin  404  and outer locating pins  405  for attaching clamping bar  403  to body  402 , and a pusher plate  406  which may be, for example spring-loaded. Body  402  includes a recess-containing member  420  containing a plurality of recesses  428  for receiving test strips therein. The pusher plate  406  includes an optional resiliently deformable band  440  for contacting the test strips during the manufacturing process. Pusher plate  406  further includes at least one outer screw  442  with a spring  444  in surrounding relation to outer screw threads  445  and at least one inner screw  446 . Pusher plate  406  can move relative to outer screw  442 . Outer screw  442  is anchored in recess-containing member  420  and remains stationary during process  500 . Inner screw  446  moves through pusher plate though a threaded inner screw hole  448  and touches but does not penetrate recess-containing member  420 . In step  510 , pusher plate  406  has been moved away from recess-containing member  420  by turning inner screws  446  clockwise. This allows placement of test strips  204  into recesses  428  (see step  520 ). Turning inner screws clockwise causes inner screws  446  to push against recess-containing member  420 , resulting in movement of pusher plate  406  away from recess-containing member  420  and compression of springs  444 . Pusher plate  406  is now spring-loaded in preparation for assembling integrated medical devices.  
         [0038]     Next, as set forth in step  520 , a previously fabricated test strip  204  with an exposed upper heat seal adhesive layer is placed in each recess  428  in assembly apparatus  400  (see  FIG. 7B ).  
         [0039]     As set forth in step  530 , a set of 10 to 50 dermal tissue penetration members  202  attached to common bandolier  454  through tabs  456  is next placed on top of test strips  204  in assembly apparatus  400  such that at least one bandolier hole  458  is aligned with central locating pin receiving hole  426  and at least one outer locating pin slot  424  (see  FIGS. 7C-7D ).  
         [0040]     Subsequently, clamping bar  403  is attached to body upper surface  416  by placing central locating and outer locating pins  404  and  405  through bandolier holes  458  and outer locating pin slots  424  and central locating pin receiving hole  426 , thereby securing bandolier  454  (see  FIGS. 7E-7F ), as set forth in step  540 . Central locating pin  404  fits securely into body  402  of assembly apparatus  400 , whereas at least one outer locating pin  405  fits into outer locating pin slots  424  in body  402 , allowing outer locating pins  405  to move as needed during the manufacturing process. Central locating pin  404  beneficially securely holds bandolier  454  in place to ensure that there is minimal movement of dermal tissue penetration members  202  in the X direction during step  560 . The combination of a fixed central locating pin  404  and moveable outer locating pins  405  beneficially improves the alignment tolerance for the dermal tissue penetration members relative to the test strips by allowing the penetration members to move on either side of the central locating pin rather than moving the entire length of the bandolier. This configuration therefore effectively halves the alignment tolerance in the X direction.  
         [0041]     As set forth in step  550 , test strips  204  are pushed toward body  402  in the Y direction by pusher plate  406  such that the reaction area on test strips  204  are aligned with lancet base  222  (see  FIG. 7G ; strips and lancet base not shown). Movement of pusher plate  406  in the Y direction is achieved by turning inner screws  446  counter-clockwise to release springs  444 . As pusher plate  406  moves in the Y direction, deformable band  440  contacts test strips  204 , subsequently pushing strips into position. Deformable band  440  beneficially accommodates variations in test strip length while ensuring that the strips are fully pushed against the base of lancet  220 .  
         [0042]     Next, assembly apparatus  400  is placed in a heat sealing apparatus and dermal tissue penetration members  202  are adhered to test strips  204  by a heat sealer  160 , as set forth in step  560  (see  FIGS. 7H-7I ). Any heat sealer known to those skilled in the art can be used in this step. Heat sealer  160  seals 2 to 20 medical devices at a time and more usually seals 5 to 10 at one time. Typical temperature, pressure and dwell times (i.e., time that the heat sealer contacts the dermal tissue penetration member) for heat sealer  160  range from 95-150° C., 15-40 N per lancet, and 1-5 seconds, respectively. The assembled integrated medical devices  200  attached to bandolier  154  (see  FIG. 6H ) are then removed from assembly apparatus  400  for further processing, i.e. for singulation by cutting through tabs  156  that connect dermal tissue penetration member  202  to the bandolier  154 .  
         [0043]     Each of the steps of process  500  can be performed, for example, either manually by a user or with the aid of a mechanical and/or electrical device.  
         [0044]     Once apprised of the present disclosure, one skilled in the art will recognize that a variety of medical devices can be beneficially manufactured according to the present invention. Such medical devices include, but are not limited to, integrated medical devices that include a combination of a test strip and a lancet, examples of which are described in the aforementioned International Application No. PCT/GB01/05634 (published as WO 02/49507 on Jun. 27, 2002) and U.S. patent application Ser. No. 10/143,399, both of which are fully incorporated herein by reference. One skilled in the art will also recognize that such test strips may have, but are not limited to, an electrochemical or photometric configuration. For illustrative purposes only, medical devices in various figures of the present disclosure were depicted as having an electrochemical configuration.  
         [0045]     Moreover, those skilled in the art will appreciate that medical devices according to embodiments of the present invention can be adapted for the measurement of, for example, glucose, ketones, glycated albumin, coagulation parameters and cholesterol of a sample.  
         [0046]     In addition, one skilled in the art will also recognize that medical devices according to the present invention may be contained within a combined sample collection and metering system designed for in-situ testing. Examples of such systems designed for in-situ testing are disclosed in International Patent Application No. PCT/US01/07169 (published as WO 01/64105 A1 on Sep. 7, 2001) and International Patent Application No. PCT/GB02/03772 (published as WO 03/015627 A1 on Feb. 27, 2003), each of which is fully incorporated herein by reference.  
         [0047]     It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.