Catalysts for body fluid sample extraction

The present invention relates to devices, arrangements, and methods that facilitate sampling, collection, and analysis of body fluids. In some embodiments, the invention may be directed to a cartridge that can be used with an integrated body fluid sampling and monitoring device.

In the description that follows, some structures and / or methods will be referred to. However, the following references should not be understood as acknowledging that these structures and / or methods constitute prior art. Applicants expressly reserve the right to prove that such structures and / or methods do not deem the prior art appropriate.

According to the American Diabetes Association, diabetes is the fifth most life-threatening illness in the United States, killing more than 213,000 people each year and bringing the total cost of diabetes to $ 132 billion in 2002. It was estimated to exceed. For every $ 10 of health care costs, $ 1 is spent on diabetes and its complications. The risk of developing type I juvenile diabetes is virtually higher than that of all other chronic pediatric disorders. Since 1987, mortality from heart disease, stroke, and cancer has declined, while mortality from diabetes has increased by 45 percent.

A crucial factor in managing diabetes is frequent monitoring of blood glucose. Currently, there are several systems for self-monitoring by patients. Most fluid analysis systems, such as systems that analyze blood samples to determine glucose content, include separate multi-components such as separate incisions, transports, and quantified portions. These systems are large, complex, and confusing to the user. These systems require significant user intervention to perform repetitive tests.

Several attempts have been made to integrate some or all of these functions. For example, a device has been developed that includes an array of disposable inspection strips. This device integrates only transport and quantification functions.

Another device attempts to integrate all three of the above functions. However, this device is useless and the user must replace the inspection strips and lancets for each inspection. This device is also very large and requires considerable user intervention. For example, the device has a separate member for creating and transporting the sample. Scratches are created by the lancet and inspection strips collect the sample. This system uses several complex mechanisms to bring the test strips to a location where they can be sampled. Finally, this device is not configured for fingertip testing.

Another device distributes one piece at a time, including an array of quantified pieces, but without the ability for automated incision or sample transport.

Yet another device includes an array of lancets and possibly a disposable insert capable of containing inspection strips. However, this device is large, cumbersome, and not wearable. This device can be expensive.

Furthermore, in these devices where such integration has been attempted, one or more mechanisms for driving the skin penetration member are provided within the reusable part of the device, but of the cartridge. Not provided inside. These drive mechanisms are overly complex and large, making it impractical to incorporate them into disposable cartridges.

In summary, most current systems that are not integrated involve a number of components that are inconvenient and make it difficult to perform inspections inconspicuously. Other current devices are somewhat integrated, but still may require significant user intervention, are prominent, overly complex, oversized, and complete the test. Requires two or more devices.

<p num="0011"> The present invention provides body fluid sample and monitoring devices and methods that can address one or more of the drawbacks noted above in connection with conventional arrangements and devices.</p><p num="0012"> Although not a requirement, the invention can provide devices, arrangements, and techniques that possess one or more of the following advantages:</p><p num="0013"> Convenience and simplicity-According to the principles of the invention, the user can carry a single disposable cartridge that can complete multiple tests.</p><p num="0014"> Reduced risk of infection and cross-contamination-Cartridges formed in accordance with the present invention allow the user to access new lancets and inspection debris for each inspection event, and contaminated articles are self-contained receptors. Ensure that it is housed and stowed inside a similarly operating cartridge.</p><p num="0015"> Reduced Environmental Contamination of Reagents-Conventional systems protect test strips from environmental contamination by storing them in plastic vials or other containers. As soon as this container is opened, all debris is exposed to the environment. This exposure can result in deterioration of the reagents contained in the test strips. According to the present invention, each reagent-containing test strip can be shielded from the environment in a chamber formed inside the cartridge.</p><p num="0016"> Improved reliability-In order to deliver the sample to the analytical section (eg, test strips), the present invention can automatically transfer the sample body fluid to the analytical section without relying on user intervention.</p><p num="0017"> Automatic Calibration and Accuracy Verification-Conventional systems typically require the user to enter a calibration code for each new set of inspection strips. This procedure can be confusing and often inaccurately performed or ignored by the user. According to the present invention, calibration information is provided on each cartridge and is automatically read by the device when the cartridge is inserted into an integrated scale or device. Similarly, each cartridge may contain one or more analysis points that act as controls. For example, when a control representing a known concentration of a sample is read and analyzed, the results obtained by the integrated scale are then compared to this known concentration. Any deviation from that concentration can be addressed and corrected, for example, by updating and modifying the algorithm used to calculate the concentration of the sample contained in the sample body fluid.</p><p num="0018"> Algorithm and Software Automatic Update Capabilities-The cartridges of the invention can be used to automatically update the software, firmware, algorithms, and / or analytical methods when the cartridge is inserted into an integrated scale or device. It can contain readable information (eg, in the form of a chip).</p><p num="0019"> As used herein, "fingers" or "fingers" means fingers or toes. "Finger fluid" means exudation of fluid from wounds created on the fingers or toes and includes the incision site on the instep or palm side of the terminal fingertip.</p><p num="0020"> As used herein, "alternative site" means a site on the body other than the fingers, such as the palm, upper arm, or thigh. "Alternative site fluid sampling" means exudation of fluid from an incision site on the surface of the body other than the fingers or toes, and includes the incision site on the palm, upper arm, or thigh.</p><p num="0021"> As used herein, "body fluid" includes whole blood, intestinal juice, and mixtures thereof.</p><p num="0022"> As used herein, "integrated device" or "integrated measuring instrument" refers to body fluid sampling, body fluid transport, sample quantification, and samples contained within body fluid samples. Means a device or scale that contains all the components necessary to perform a quantity display.</p>

<p num="0023"> According to one aspect, the present invention relates to an arrangement comprising a housing and a plurality of sampling and analysis portions built therein, such that each of the sampling and analysis portions penetrates the skin. A skin-penetrating member having a configured first end and a lumen communicating with the first end, an actuator actionably associated with the skin-penetrating member, and a sample fluid-communication with the lumen of the skin-penetrating member. It is provided with a quantification member.</p><p num="0024"> According to another aspect of the invention, the invention relates to an integrated measuring instrument or device having the above identified arrangement.</p><p num="0025"> The following description of preferred embodiments can be read in conjunction with the accompanying drawings in which similar numbers refer to similar elements.</p>

According to the first aspect of the present invention, an arrangement and technique for sampling and analyzing a body fluid are provided for measuring the concentration of a target sample contained in the body fluid. Target specimens include, but are not limited to, glucose, bilirubin, alcohol, regulated substances, toxins, hormones, proteins and the like. These arrangements and techniques are suitable for use when sampling body fluids from fingers or alternative sites.

In general, the arrangement of the present invention may comprise a disposable arrangement. This disposable arrangement can be in the form of a cartridge. The invention also includes an integrated scale that comprises a reusable portion as well as a disposable arrangement (eg, a cartridge). The cartridge may include an array of skin-penetrating elements attached to guides, triggers, and / or drive mechanisms. The cartridge may also include a mechanism for transporting a sample of body fluid from the skin surface into other areas of the device. According to some embodiments, at least part of the transport operation is incorporated into the skin penetrating element. The cartridge may also include a sample quantifying member that may be separate from or integrated with the transport member. The sample quantifier may be designed to show detectable changes optically or electrochemically when exposed to the sample of interest. The cartridge may also include one or more skin contactors, possibly a soft silicone footprint. These one or more skin interface members or footprints may optionally be composed of any material that facilitates sample availability by skin conditioning before, during, and / or after perforation. Alternatively, one or more of these skin contactors may be included within the reusable portion of the device. The disposable part may include an energy source. The disposable portion may also include a housing designed to enclose and / or encapsulate the sample medium. The disposable portion may also include or be designed to allow a user-adjustable skin penetration depth. The disposable portion can also include not only a vacuum chamber but also means for providing an airtight seal in contact with the skin. Finally, the disposable portion may contain readable information that can be used for calibration, control, or software update purposes.

Arrangements formed according to one typical embodiment of the present invention are illustrated in FIGS. 1-6. As illustrated in these figures, this arrangement can generally be provided in the form of replaceable cartridges 10. The cartridge 10 includes a housing 12. The housing 12 may be constructed of any suitable material. For example, the housing 12 may be made of a molded polymer material.

The housing 12 may be provided in any suitable form. One optional configuration is illustrated in Figures 1-3. As illustrated, the housing 12 comprises a footprint ring 14. The footprint ring 14 comprises a plurality of holes 16 arranged around its circumference. The footprint ring 14 may optionally include a plurality of footprints 17 that surround each hole 16 and are attached to the footprint ring 14. Each footprint 17 is configured to be placed at a sampling site on the user's skin surface. The footprint 17 can be annular in shape according to the illustrated examples. However, the footprint is not limited to this shape or configuration. Numerous shapes or configurations can satisfy the function of providing a footprint around a site on the surface of the skin where fluid should be exuded, i.e. a sampling site. According to some embodiments, the footprint 17 is composed of a material that facilitates the formation of a seal between the skin and the footprint 17. For example, materials suitable for this purpose include relatively soft rubber elastic materials such as silicone rubber. The footprint 17 can be formed to have any suitable size. For example, the footprint 17 may have an opening having a diameter of about 3-8 mm or a main dimension of about 3-8 mm. Alternatively, a footprint is provided for the same purposes as part of an integrated scale or device in which this arrangement or cartridge 10 can be placed, as described in more detail herein. Can be done.

According to the illustrated embodiment, the housing 12 further comprises a transparent optical window 18. The transparent optical window 18 may be provided, for example, to allow optical communication between the detector and one or more components embedded in the arrangement or cartridge 10.

The housing 12 may further include an upper lid 20. An inner frame 22 may also be provided. The inner frame 22 can help define the plurality of analytical portions 24 at the cartridge interior 10.

One beneficial aspect of the arrangement or cartridge 10 of the present invention is that the arrangement or cartridge 10 can be used to retain information that is readable by the device into which it is inserted. Such information can be used to update the data and / or code used by the device, and can also be used for accuracy verification and calibration purposes. Various mechanisms that may be associated with cartridges are suitable for the accomplishment of this purpose, as will be apparent to those skilled in the art. Two typical mechanisms are illustrated in Figure 3. That is, the cartridge 10 may include a mechanism such as a readable memory chip 21 that holds information and / or code that can be read by the device into which the cartridge 10 is inserted. The mode in which the data and / or code is read from the chip 21 was included on the memory chip, such as electrical contacts and direct optical communication such as radio frequency identification / transmission or infrared radiator and detector systems. It may have any conventional arrangement for reading information. Another mechanism capable of providing data and / or other information to the device into which the cartridge 10 is inserted is illustrated in FIG. 3 as having a barcode 23 or similar optically readable mechanism. The barcode 23 is positioned on the outside of the cartridge so that an optical sensor positioned inside the integrated scale can read the information contained within the bar. Optical sensors and processors inside the integrated device can convert bar patterns into data, as is commonly known in other areas such as over-the-counter scanners. The data read from the barcode is used to access a particular algorithm or look-up table stored inside the memory inside the integrated scale. This data allows the integrated device to be adjusted to any difference when manufacturing disposable cartridges. Suitable sensors / detectors for reading chip 21 and / or barcode 23 are schematically illustrated as element S / D in FIG.

Another beneficial aspect of this arrangement described above is the availability of one or more analytical portions 24 for calibration and control purposes. In general, one or more analytical parts 24 can be used for checking the accuracy of inspection readings and for automatic system calibration to compensate for any possible variations in the operation of the device. One such technique and arrangement is illustrated in Figures 4A-4B. As illustrated in these figures, one and potentially multiple analytical portions 24 are provided with a hub 32 that includes a control test pad 30'. The control test pad 30'is provided with three separate regions, each of which produces a known reflectance value. That is, a first region X with a first darker color, a second uncolored region Y, and a third brightly colored region. When the control test pad 30'is read by the detector D'through the transparent window 18, the pixels of the detector D'corresponding to each of the regions X, Y, and Z generate a reflectance reading. This detection is shown in Figure 4B. As illustrated in the figure, the reflectance value actually measured by the detector D'can differ from the known reflectance value of the control test pad 30'. This difference can be analyzed and compensated for by any suitable technique. For example, the algorithm used to calculate the sample concentration level can be adjusted to compensate for this difference, thereby producing more accurate results. Such control and calibration operations may be performed after each test or after several tests.

Alternatively, the control fluid can be released into the test pad and reacted with the chemical reagents contained therein. Since the control fluid contains a known concentration of the sample, then the measured concentration of the sample is compared to this known concentration and any differences can be analyzed and compensated for as described above.

Each of the sampling and analysis portions 24 of the illustrated examples comprises a skin penetrating member 26. Each skin penetrating member 26 can take any suitable form. According to the illustrated examples, each skin penetrating member 26 is in the form of a hollow needle, not only the first portion of the portion 26e configured to penetrate the skin, but also the lumen 26l. Has (Fig. 5). It should be understood that alternative skin-penetrating members consistent with the principles of the present invention (eg, solid lancets, etc.) can also be utilized. The at least one skin penetrating member 26 may take any suitable form. For example, the at least one skin penetrating member may include a solid lancet or a hollow needle. According to one embodiment, the skin penetrating member 26 is in the form of a so-called "microneedle". As the name suggests, microneedle is characterized by its relatively small outer diameter. For example, a microneedle may include a skin penetrating member having an outer diameter on the order of 40-200 μm, as the term is used herein. Its inner diameter can vary, but has, for example, an inner diameter on the order of 25-160 μm. Needles can be characterized by being referred to in the art as "gauges". By way of example, and consistent with the above description, microneedles with gauges ranging from 26 to 36 are expressly included by the present invention. Several advantages can be found from the use of such microneedles as skin-penetrating members. In particular, due to its small size, the size of the wound left upon entry into the skin is relatively small, thereby minimizing the pain associated with such needle insertion and allowing for a faster healing process. However, of course, the present invention is not limited to the use of such a microneedle. Thus, for example, according to one possible alternative embodiment, these one or more skin penetrating members may contain a hollow needle having a gauge of about 20-25 gauge or be about 0.018 cm (about 0.007). Includes hollow needles with an inner diameter of (inches) and an outer diameter of about 0.051 cm (about 0.020 inches).

At least one skin-penetrating member can be formed from any suitable material, such as metal, plastic, glass, etc.

Each skin penetration member can be attached to the hub 32. Each hub 32 is then attached to the actuator 28. It should be understood that several different actuators are available according to the principles of the present invention. The actuator can be mechanical, electric, pneumatic or the like. According to the illustrated embodiment, the actuator 28 is in the form of a torsion spring. When activated, the torsion spring drives the hub 32 to allow its attached skin-penetrating member 26 to enter the user's skin through each of the holes 16. According to some examples, each sampling and analysis portion 24 further comprises a sample quantifying member that produces a detectable signal when contacted with a target sample contained within a sample of body fluid. Be prepared. Several suitable members are contemplated. These members can be based on conventional techniques such as photometry or electrochemical analysis. According to the illustrated examples, a assay pad 30 is provided on each hub 32, which generally contains a chemical reagent that causes a chemical reaction that results in a detectable signal when reacting with the target specimen. Contains absorbent material. The test pad 30 is in fluid communication with the lumen 26e of the skin penetrating element 26. As noted above, this signal can be detected optically, electrochemically, or by other suitable means. According to one embodiment, the assay pad 30 produces spots that are optically detected by any suitable arrangement or technique upon reaction with the target specimen. For example, as schematically illustrated in FIG. 5, the test pad 30 may be placed on the outer surface of the hub 32 and held in place by a retaining element or lid 34. The retaining element or lid 34 can take any suitable form, such as a cap that snaps onto the hub 23, or a piece of adhesive. The retaining element or lid 34 is preferably transparent. Therefore, the spots generated on the test pad 30 by the above reaction can be optically observed through the transparent optical window 18 formed along the internal region of the illustrated cartridge housing 12.

Here, various mechanisms that trigger the drive of the hub 32 and the attached skin-penetrating member 26 will be described.

In the typical, non-restrictive arrangement illustrated in FIGS. 5-6, the actuator 28 is in the form of a torsion spring with a rear leg 36 and a front leg 38. The front leg 38 is secured to the hub 32 by any suitable means, such as the illustrated perforations in the hub 32. The hub 32 is further provided with a mechanism for freely capturing the rear leg 36 of the torsion spring. According to the illustrated embodiment, this releasable capture mechanism comprises an open lock groove 40 configured to receive the hind legs 36. When the hind legs 36 are placed inside the releasable capture mechanism, the groove 40, the hind legs 36 and the front legs 38 are compressed toward each other. In this state, the torsion spring has an eccentric force that tries to compress the rear leg 36 and the front leg 38 so as to separate them. Therefore, to drive the skin-penetrating member 26 and the attached hub 32, the hind legs 36 are released from the open lock groove 40 by any suitable mechanism or technique. As illustrated in FIG. 6, the hind leg 36 is squeezed out of direct contact with the groove 40 by moving it in the direction indicated by arrow A. The hind leg 36 is substantially prevented from moving by being trapped inside the inner frame wall W, while the front leg 38 is relatively unrestrained. As a result of the natural eccentric force of the torsion spring that compresses the hind and front legs 36, 38 apart, the hub 32 and the attached skin-penetrating member 26 pass the skin-penetrating member 26 through each hole 16. It is squeezed by a downward movement in an arc so that it enters the surface of the user's skin. The hub 32 can rotate around the pivot or pin 42 when driven.

FIGS. 7-10 exemplify other optional embodiments of the trigger mechanism configured according to the principles of the present invention. As illustrated in FIG. 7, the trigger mechanism 50 is provided for the purpose of compressing the rear leg 36 of the actuator 28 and dislocating it from the locking groove 40. According to exemplary and non-limiting embodiments, the trigger mechanism 50 comprises a drive portion 52 such as a motor, solenoid, or servo device and a driven linear actuator arm 54. According to some optional embodiments of the present invention, in order to protect the components housed inside the cartridge from environmental contamination and to facilitate the creation of vacuum pressure in the analytical portion 24. It may be recommended to seal each analytical section. It is noted that the arrangement illustrated in FIG. 7 has an opening 16 corresponding to a hole contained within the footprint ring 14, which is the manner in which the cartridge 10 is described above. Sealed when applied to the surface of the skin. For example, as illustrated in FIG. 7, an opening 55 is provided in the frame 22 to allow the introduction of the linear actuator arm 54. The opening 55 can be sealed by a flexible solid membrane 56. The membrane 56 allows the linear actuator arm 54 to move to the extent necessary to separate the hind leg 36 of the actuator 28 from the lock groove 40, but sufficiently enough that this movement does not penetrate or destroy it. It is flexible.

A similar configuration is illustrated in FIG. However, in the embodiment illustrated in FIG. 8, the opening 55, in combination with a secondary seal 60 placed around the linear actuator arm 54, allows penetration of the linear actuator arm 54. It is sealed by combining a perforated membrane 58 having an opening to be formed. As illustrated, the secondary encapsulant 60 is designed to make firm contact with the perforated membrane 58 when the driven linear actuator arm 54 is inserted into it. Therefore, the sealant is maintained through the opening 55 in the frame 22 for the purposes described above. As further illustrated in FIG. 8, one or more openings 16 in the cartridge can be optionally sealed by any suitable mechanism or member, such as the thin sealing film 17s. The seal 17s allows each chamber to remain fully sealed until it is pierced. The encapsulant can be removed by the user when loading a new disposable cartridge, or can actually be pierced by the skin-penetrating member 26 as it penetrates the user's skin. It should be understood that this aspect of the examples illustrated in FIG. 8 may apply to any of the various examples described in this application.

Other variants of the above arrangement are illustrated in FIGS. 9-10. As illustrated in these figures, the opening 55 in the frame 22 is sealed by a penetrable membrane sealer 62. The perforable membrane sealer 62 usually has a solid structure. However, the perforable membrane sealer 62 is provided with a weakened portion or a perforation 64 (FIG. 10) that facilitates the creation of an opening in the membrane upon contact with the driven linear actuator arm 54. Can be done. When the linear actuator arm portion 54 is inserted from the weakened portion or the perforated portion 64, a passage is formed inside the membrane sealing body 62 through which the passage can be penetrated. However, relatively close contact is maintained between the newly formed opening in the piercing membrane sealer 62 and the linear actuator arm 54. This contact serves to maintain at least a significant sealing effect.

Examples of other alternative methods of the trigger mechanism formed according to the principles of the present invention are illustrated in FIGS. 11-20. As illustrated in FIG. 11, the linear actuator arm 54 moves through the opening 55 in the direction of arrow B. The opening 55 can be sealed by any suitable mechanism or structure, such as any of the sealing mechanisms described above. Linear actuator shown by the broken line in FIG. 11 As shown by the relative position of the arm 54 and the hind leg 36, the arm 54 has an actuator in such a manner that it is pushed out from the engagement with the lock groove 40. An angled ramp surface 66 designed to interact with the hind legs 36 is provided.

Other changes in the arrangement of FIG. 11 are illustrated in FIG. According to this change, the linear actuator arm 54 moves a predetermined distance in the direction of the arrow C, as shown by the relative position of the linear actuator arm 54 and the hind leg 36 shown by the broken line in FIG. A curved or arcuate ramp surface 68, similarly designed to interact with the rear leg 36 of the actuator, is then provided in a manner that pushes it out of engagement with the lock groove. Again, the opening 55 can be sealed by any suitable means, such as any of the sealing structures described above.

Another embodiment of the trigger mechanism formed according to the present invention is illustrated in FIG. According to this embodiment, the pivotable actuator arm 70 is provided to move within the opening 55. The opening 55 can be sealed by any suitable mechanism, such as any of the sealing structures described above. The pivotable arm 70 translates or pivots in the direction indicated by arrow D, thereby causing the actuator hind leg 36 from engaging with the lock groove 40, as shown by the dashed line in FIG. It is configured and arranged to be forcibly removed. The pivotable arm 70 can be driven by any suitable conventional mechanism, such as a motor, solenoid, or servo device.

A trigger mechanism configured according to yet another embodiment of the present invention is illustrated in FIG. According to this embodiment, the linear actuator arm portion 72 having the same structure as the structure of the linear actuator arm portion 54 described in the previous embodiment is provided. However, the linear actuator arm 72 is oriented at a position deviated by 90 ° from the position of the linear actuator arm 54 described above. As illustrated in FIG. 14, the linear actuator arm 72 is positioned to move in the direction of arrow E, thereby directing the second end 36 of the actuator to a position adjacent to the bottom of the lock groove 40. Engage and push this end out of engagement with the lock groove 40, as illustrated by the dashed line in FIG. As with the embodiment described above, the opening 55 can be sealed by any suitable mechanism, such as any of the sealing arrangements described above.

As illustrated in FIGS. 15A-15B, a suitable alternative trigger mechanism is configured by providing a pivotable drive arm 74 that moves in the direction indicated by the arrow F inside the opening 55. sell. When the pivotable drive arm 74 moves in the direction indicated by the arrow F, the second leg 36 is forcibly disconnected from the lock groove 40 in the direction indicated by the arrow G. An angled ramp surface 76 configured to interact with the hind legs 36 of the actuator is provided. The opening 55 can be sealed by any suitable mechanism, such as any of the sealing mechanisms described above.

Other alternative trigger or release mechanisms and arrangements formed in accordance with the present invention are illustrated in FIGS. 16-19. According to this embodiment, the hind legs 36 of the actuator 28 are fixed and held in a lock feature structure 80 (eg, FIG. 18) within a pin or axis 42. The front leg 38 of the actuator 28 is fixed and held by the hub 32. The hub 32, actuator 28, and pin or pivot 42 are mounted inside chamber 81 defined by cell walls 82, 84. According to the illustrated embodiment, the pivot or pin 42, the attached hub 32, and the actuator 28 are held between the cell walls 82, 84 by a retaining groove 90 located in the cell wall. The hub 32 is locked to the position where it was first raised (eg, FIGS. 16-17) by the interaction between the locking feature structure associated with the hub 32 and the locking feature structure associated with the chamber 81. It is positioned inside the chamber 81 so as to. According to this exemplary embodiment, the locking feature structure associated with chamber 81 comprises a pair of protrusions 86, each protrusion extending from each cell wall 82, 84, and locking features associated with hub 32. The structure comprises a pair of laterally spaced grooves or recesses 88 configured to fit freely into the protrusions 86. Numerous changes to the illustrated lock feature structure are contemplated. For example, the positions of the protrusions 86 and the grooves 88 can be replaced. Furthermore, the cooperating protrusions and grooves can have a number of different geometric configurations.

When the hub 32 is positioned in the locked position within the chamber 81, the hind legs 36 and the front legs 38 are biased away from each other, and thus when the lock feature structures 86, 88 (FIG. 19) are disengaged, the skin penetration member 26 The hub 32 and the attached skin-penetrating member 26 are squeezed by an arcuate downward movement so that is penetrated into the surface of the user's skin. Lock feature structures 86,88 are removed by applying force to hub 32, for example, as indicated by arrow F (FIG. 19). Any suitable mechanism, such as those mechanisms previously described herein, can be utilized to apply the force required to disengage the hub.

Another optional trigger mechanism configured according to the principles of the present invention is illustrated in FIG. 20, where the trigger mechanism 50 is attached to a peripheral member that is relatively stationary with one end attached to the hub 32. It is provided for the purpose of cutting the wire or fuse 92 having the other end. According to exemplary and non-limiting embodiments, the trigger mechanism 50 includes a portion 94, both of which may include at least one of a cutting member or heating element capable of cutting the restraining wire or fuse 93. The opening 55 can be optionally sealed by any of the sealing arrangements described above.

Arrangement 10 may constitute at least a portion of a device that functions to only sample body fluids. For example, arrangement 10 can be used to exude fluid in the form of blood droplets that collect on the surface of the user's skin. The blood droplets are then transferred to another separate device, which then transports and / or analyzes the sample for the target specimen. Alternatively, arrangement 10 can exude a sample of bodily fluid from finger D and then transport the sample to a next accessible location for further analysis by a separate device. For example, the sample body fluid can be transported to a reagent-containing pad also incorporated in arrangement 10. The sample then reacts with the reagent to produce a detectable spot or signal. The reagent pad can then be analyzed by a separate instrument using photochemical, electrochemical, or other suitable techniques known to those of skill in the art. During the analysis described above, the reagent pad may remain inside arrangement 10. Alternatively, the reagent pad can be removed from arrangement 10 and inserted into a separate device such as an electrochemical or photometric meter.

According to another aspect of the invention, the arrangements and techniques described above may form at least a portion of the integrated device, as previously described herein. As noted earlier, as used in the present invention, the terms "integrated device" or "integrated measuring instrument" are used to sample body fluids, transport body fluids, quantify samples, and in sample body fluids. Means a device or measuring instrument that includes all the components necessary to display the amount of sample contained in. Therefore, according to the principles of the present invention, an integrated device or instrument may include one or more of the feature structures described earlier herein, or any combination. According to another aspect of the invention, the integrated scale or device may include additional components and / or feature structures as described below.

Although not a requirement, it is understood that the trigger mechanism described above can form part of a separate sampling device or part of an integrated device in which the cartridge 10 is housed. Should be.

One such integrated measuring instrument is illustrated in FIGS. 21-23. As illustrated in these figures, the integrated scale 100 typically includes a housing 112. The integrated scale 100 may further include a footprint 114 of the type described above. The door 116 may be provided on top of the housing 112. The door 116 is connected to the housing 112 via a hinge 118. As illustrated in FIGS. 22-23, the door 116 can be opened to expose the cartridge 10 containing the plurality of skin penetrating elements and analytical portions, as previously described herein. In the illustrated embodiment, the integrated measuring instrument 100 further includes a display 120 for communicating the analysis result of the sample body fluid regarding the presence and / or concentration of the sample contained in the sample body fluid. The integrated scale 100 may further include one or more buttons 122 that may be pressed by the user to link the various functions and interfaces of the integrated scale 100.

FIG. 22 is an example of an integrated scale 100 in which the door 116 is open to expose other details of the internal components of the integrated scale 100. As illustrated in that figure, the housing 112 contains a cartridge 10. In the illustrated embodiment, the cartridge 10 is circular and includes a plurality of skin penetrating elements and analytical portions. The cartridge 10 is mounted around the central hub 122 and is rotatable on it. Therefore, at the time of sampling, the skin-penetrating element is driven through an opening in the housing that is aligned with the footprint 114 to penetrate the user's skin. Once the test is complete, the cartridge 10 will align the unused skin penetration element with the opening in the enclosure and the corresponding opening in the footprint 114 in preparation for the next sampling event. Can be rotated to. It should be understood that the present invention is not limited to the exemplary circular cartridges having the particular configuration shown in the drawings. Without limitation, several alternative cartridge configurations are possible, such as a slidable linear or polygonal configuration (not shown). FIG. 22 also illustrates the presence of a light source 124 located behind the door 116. The light source 124 can take any suitable form, such as a light emitting diode. It should be understood that alternative light sources are also available. The function of the light source 124 is described in more detail below.

In this regard, the light emitted from the light source 124 is incident on the test pad (eg, 30) and reflected from its surface. When reaction spots are formed on the surface of the test pad, the amount of light reflected from the reaction spots is different from the light reflected from other parts of the reagent pad that do not contain such reaction spots. This reflected light is captured by the detector 126. The detector 126 may include a lens 128 and a photodetector element 130.

The photodetector 130 comprises one or more detector elements. According to one alternative structure, the detector element 130 comprises a plurality of detector elements formed in an array. This array can be of any suitable configuration and, according to one non-limiting example, can be a linear array. The detector element may have any suitable structure. For example, the detector element 130 may include a photodiode, a CCD, or a CMOS-based detector element. The signal transmitted to the detector element 130 is passed to a suitable electronic device built into the housing 112 via a suitable electrical connector such as the flexible ribbon 131 (FIG. 23). The details of electronic devices and signal interpretation are familiar to those skilled in the art. Although not a requirement to enable the practice of the invention claimed in this application, further details regarding the structure, function and arrangement of the analytical part and the components contained therein are provided in "DEVICE FOR FLUID ANALYSIS WITH SAMPLE". EXTRACTION AND The entire content, entitled "TRANSPORT," may be collected from the disclosure contained in US Patent Provisional Application No. 60/721966, which is incorporated herein by reference. Similarly, although not a requirement to enable the practice of the invention claimed in this application, further details regarding the structure, function, and arrangement of the detector 126, as well as its components, are described in "ANALYTE". DETECTION DEVICES AND METHODS WITH HEMATOCRIT / VOLUME CORRECTION AND FEEDBACK CONTROL ", the entire contents of which may be collected from the disclosure contained in US Patent Application No. 11/239122, which is incorporated herein by reference.

An integrated measuring instrument incorporating an arrangement formed according to the present invention can be used not only for finger fluid sampling and analysis, but also for alternative site fluid sampling and analysis that can be performed at any location at the user's discretion. It is configurable.

As is clear from FIGS. 21-23, the integrated measuring instrument 100 is configured for handheld use. However, the present invention is not limited to the handheld device. For example, the present invention also relates to a wearable integrated measuring instrument. An example of such a wearable device is illustrated in FIG. The wearable integrated device 200 illustrated in this figure may generally consist of a functional portion 202 and a body-worn portion 204. The functional portion may comprise an arrangement 10 of the type described herein. The functional part may also have one or more characteristic structures and elements of the handheld integrated scale described above.

As noted earlier, according to some embodiments of the invention, the concentration of the sample contained in the body fluid sample is queried by the test pad with a light source, whereby the detector is the sample and the test pad. It produces a signal indicating the color change caused by the reaction with the reagent contained in the sample, which is then measured using a photometric technique associated with the concentration of the sample contained in the sample. sell.

The present invention relates to a photometric device and an arrangement, and these devices and arrangements can be small, stand-alone, wearable or handheld, and can be inspected multiple times without exchanging inspection components. Techniques and techniques that facilitate incorporation into the types of devices and arrangements described are provided.

According to the first embodiment, a photometric analytical arrangement configured to satisfy at least the objectives noted above is illustrated in FIG. As illustrated in this figure, the arrangement 300 typically comprises a platform or stage 302, multiple assay pads 304 containing chemical reagents, a single light source 306, and a single detector 308. The light source 306 can be provided by any suitable device such as a light emitting diode (LED), as well as the detector of one or more CMOS, CCD, photodiodes, or infrared detector elements. It is possible to include any suitable device such as. According to one embodiment, the detector 308 includes an array of CMOS detector elements.

According to Arrangement 300, these plurality of test pads 304 are provided in a fixed position with respect to the platform or stage 302. Therefore, relative movement between the test pad 304 and the platform 302 is not possible. The light source 306 and the detector 308 are also provided in a fixed position separate from the platform or stage 302. The light source 306 is arranged to guide light towards a particular test pad 304 when aligned with the test pad 304. Similarly, the detector 308 is arranged to receive the light reflected from the test pad positioned in place. Platform 302 is rotatable such that each of the plurality of test pads 304 can be indexed and aligned with light source 306 and detector 308 for analysis, as indicated by the arrows included in FIG. Is.

A variant of Arrangement 300 is shown in Figure 26. The arrangement 400 is configured to share much of the same feature structure as previously described in connection with the arrangement 300 above. According to Arrangement 400, platform 302 is fixed and non-rotatable. Both the light source 306 and the detector 308 are mounted on a second platform or stage 402. Both the light source 306 and the detector 308 are located in a fixed position with respect to the platform 402 so that relative movement between them is not allowed. According to arrangement 400, each of the individual test pads 304 is determined by rotating the second platform 402 in the manner indicated by the arrow visible in FIG. 26, or the light source 306 and the detector. Aligned with 308.

Other optional changes to arrangements 300, 400 are shown in Figure 27. According to Placement 500, Platform 302 is fixed and not mobile. Both the light source 306 and the detector 308 are mounted on the indexing arm 502 in a fixed manner. According to Arrangement 500, the light source 306 and the detector 308 are indexed by rotating the movable indexing arm 502 in the manner indicated by the arrow visible in FIG. 27, or the test pad 304. Aligned with each of the. Therefore, the light source 306 and the detector 308 are brought up to a position located above the selected test pad 304. According to this arrangement 500, light is emitted downward from the light source 306 toward the test pad 308. At least a portion of this light is then reflected approximately upward from the test pad 304 so that it is then received by the detector 308.

In some cases, eliminating the need to move the test pad 304 relative to these components in order to selectively identify or align the light source 306 and detector 308 for analysis. Can be advantageous.

One such arrangement that achieves this goal is illustrated in Figure 28. According to Arrangement 600, each of the plurality of test pads 304 can be individually queried without the need to provide relatively movable components within the system. According to the illustrated arrangement 600, a plurality of optical pipes or similar optical transmission elements 602 are provided to communicate between each of the single static light source 306 and the plurality of test pads 304. The detector 604 is positioned so that it can receive the light reflected from each of the individual test pads 304. To this end, the detector 604 can be partitioned or formed as an array of individual detector elements, as illustrated in FIG. Therefore, the detector 604 comprises a plurality of sections, each of which is directed to receive the light reflected from the selected test pad 304. The light emitted from the light source 306 may be multiplexed or selectively transmitted to a particular test pad 304. This multiplex transmission can be achieved by any suitable technique known to those of skill in the art.

One possible variant of arrangement 110 is shown in Figure 29. According to Arrangement 700, as with Arrangement 600, multiple analytical parts can be queried without the use of relatively mobile components. According to Arrangement 700, all of the test pads 304 are provided with a single light source 306 that simultaneously transmits light. A plurality of detector elements 702, 704, 706 are provided, and each of these detectors is aligned and positioned with the light reflected from each of the test pads 304. Multiple detector elements 702, 704, 706 may be multi-driven or selectively driven to read only the desired test pad 304. This multiple drive can be achieved by any suitable technique known to those of skill in the art.

Typical, but not necessarily limited, fluid sampling and analysis methods or techniques that can be used with any of the above arrangements, devices, or integrated scales are described as follows.

The user loads a new disposable cartridge containing multiple skin penetration members and analytical sections into the integrated scale. The integrated scale then reads the calibration data contained in or on the cartridge. This data can be read in any suitable manner. For example, a barcode that can be optically read by an optical assembly built into the scale can be placed on top of the cartridge. Alternatively, the data may be contained on a chip carried by a cartridge that is read when inserted into the integrated scale. The integrated scale then selects the appropriate look-up table or algorithm to calculate the total glucose readings taking into account the calibration data. The scale can then be placed in ready mode waiting for a trigger to initiate sampling and testing. The user then manually presses a button or trigger to initiate sampling and analysis, or the device is equipped with the instrument properly positioned on the user's skin for sampling and analysis procedures. Make sure you are ready to start. Suitable sensors to achieve this include optical, capacitive, or pressure sensors. The device then activates a promoter that acts to facilitate the exudation of body fluids. According to one alternative embodiment, the facilitator is an inflatable member that applies pressure to the finger. Alternatively, the accelerator is a vacuum pressure that produces a suction force at the sampling site. The sensors present in the scale can be used to monitor and control the positive or negative pressure of the accelerator. After achieving the target pressure for the desired time, a skin penetrating member (eg, a hollow needle) is driven to create a wound site and is pushed into the user's skin. The skin-penetrating member rests in or in direct contact with the wound created at the sampling site at the desired location where it collects a sample of bodily fluid exuded from the wound. The integrated scale may further include a mechanism for detecting whether a sufficient amount of sample has been exuded. Details of such an appropriate detection technique can be found in "ANALYTE". Titled "CONCENTRATION DETECTION DEVICES AND METHODS", the entire contents of which are described in detail in US Pat. No. 7052652, which is incorporated herein by reference. Once the desired fluid volume is obtained, the accelerator is stopped. A sample of body fluid communicates fluidly with a device or mechanism that produces a detectable signal when it reacts with a sample present in this sample body fluid. For example, one such mechanism is an absorbent pad containing a chemical reagent, which, when reacted with a sample, produces a reaction spot that can be detected optically. Using the optical assembly that communicates with the signal generation mechanism described above, the signal generated by the reaction with the sample is detected and the signal is communicated to the support electronic device built in the measuring instrument. The concentration of the target sample (eg, glucose) can then be calculated using these signals as a reference. Additional factors such as sample size, levels of other substances contained in the sample (eg, hematocrit values), etc. can be considered in these calculations. Such an optional calculation technique is entitled "ANALYTE DETECTION DEVICES AND METHODS WITH HEMATOCRIT / VOLUME CORRECTION AND FEEDBACK CONTROL" and is incorporated herein by reference in its entirety. It is explained in more detail in. These calculations quantify the amount of sample contained in the sample body fluid. This quantification is displayed on a suitable indicator built into the scale, which can be easily read by the user. The integrated scale then automatically indexes the disposable cartridge to present a new unused skin penetration member that will be used to perform the next sampling and analysis event. Titled METHODS, the entire content is described in detail in US Pat. No. 7052652, which is incorporated herein by reference in its entirety. Once the desired fluid volume is obtained, the accelerator is stopped. A sample of body fluid communicates fluidly with a device or mechanism that produces a detectable signal when it reacts with a sample present in this sample body fluid. For example, one such mechanism is an absorbent pad containing a chemical reagent, which, when reacted with a sample, produces a reaction spot that can be detected optically. Using the optical assembly that communicates with the signal generation mechanism described above, the signal generated by the reaction with the sample is detected and the signal is communicated to the support electronic device built in the measuring instrument. The concentration of the target sample (eg, glucose) can then be calculated using these signals as a reference. Additional factors such as sample size, levels of other substances contained in the sample (eg, hematocrit values), etc. can be considered in these calculations. Such an optional calculation technique is entitled "ANALYTE DETECTION DEVICES AND METHODS WITH HEMATOCRIT / VOLUME CORRECTION AND FEEDBACK CONTROL" and is incorporated herein by reference in its entirety. It is explained in more detail in. These calculations quantify the amount of sample contained in the sample body fluid. This quantification is displayed on a suitable indicator built into the scale, which can be easily read by the user. The integrated scale then automatically indexes the disposable cartridge to present a new unused skin penetration member that will be used to perform the next sampling and analysis event. Titled METHODS, the entire content is described in detail in US Pat. No. 7052652, which is incorporated herein by reference in its entirety. Once the desired fluid volume is obtained, the accelerator is stopped. A sample of body fluid communicates fluidly with a device or mechanism that produces a detectable signal when it reacts with a sample present in this sample body fluid. For example, one such mechanism is an absorbent pad containing a chemical reagent, which, when reacted with a sample, produces a reaction spot that can be detected optically. Using the optical assembly that communicates with the signal generation mechanism described above, the signal generated by the reaction with the sample is detected and the signal is communicated to the support electronic device built in the measuring instrument. The concentration of the target sample (eg, glucose) can then be calculated using these signals as a reference. Additional factors such as sample size, levels of other substances contained in the sample (eg, hematocrit values), etc. can be considered in these calculations. Such an optional calculation technique is entitled "ANALYTE DETECTION DEVICES AND METHODS WITH HEMATOCRIT / VOLUME CORRECTION AND FEEDBACK CONTROL" and is incorporated herein by reference in its entirety. It is explained in more detail in. These calculations quantify the amount of sample contained in the sample body fluid. This quantification is displayed on a suitable indicator built into the scale, which can be easily read by the user. The integrated scale then automatically indexes the disposable cartridge to present a new unused skin penetration member that will be used to perform the next sampling and analysis event. Titled CONTROL, the entire content of which is described in more detail in US Patent Application No. 11/239122, which is incorporated herein by reference in its entirety. These calculations quantify the amount of sample contained in the sample body fluid. This quantification is displayed on a suitable indicator built into the scale, which can be easily read by the user. The integrated scale then automatically indexes the disposable cartridge to present a new unused skin penetration member that will be used to perform the next sampling and analysis event.

It should be understood that the components, constituents, numbers representing the quantity of reaction conditions, etc. used herein are modified by the word "about" in all cases. The numerical ranges and parameters that describe the broad scope of the subject matter presented herein are approximations, but the numbers given are shown as closely as possible. However, each number inherently contains some error due to the standard deviation found in each of these measurement techniques. None of the elements described in the appended claims are incorporated by the United States Code, Vol. 35, Article 112, Paragraph 6 unless the term "means" is explicitly used.

The present invention has been described in the context of its preferred embodiments, but without departing from the spirit and scope of the appended claims, additions, deletions, modifications, and substitutions not specifically described. Will be understood by those skilled in the art.

<figref num="1">It is a perspective view of the arrangement constructed according to this invention.</figref><figref num="2">It is a perspective view of a part of the arrangement of FIG.</figref><figref num="3">It is an exploded assembly drawing of the arrangement of FIG.</figref><figref num="4A">It is a schematic diagram of the control / calibration mechanism which can be used together with the arrangement of FIG.</figref><figref num="4B">It is a schematic diagram of the control / calibration mechanism which can be used together with the arrangement of FIG.</figref><figref num="5">It is a side view of the skin penetration member, the hub, and the actuator of the arrangement of FIG.</figref><figref num="6">It is a top view of the skin penetration member, the hub, and the actuator of the arrangement of FIG.</figref><figref num="7">It is a side view of the trigger mechanism of the actuator according to one Embodiment of this invention.</figref><figref num="8">It is a side view of the trigger mechanism of the actuator according to the Example by another method of this invention.</figref><figref num="9">It is a side view of the trigger mechanism of the actuator according to another embodiment of this invention.</figref><figref num="10">It is a top view of the optional sealing member for the trigger mechanism of FIG. 9 of the present invention.</figref><figref num="11">It is a top view of the trigger mechanism according to the optional embodiment of this invention.</figref><figref num="12">It is a top view of the trigger mechanism according to another embodiment of this invention.</figref><figref num="13">It is a top view of the trigger mechanism according to still another embodiment of this invention.</figref><figref num="14">It is a top view of the trigger mechanism according to still another embodiment of this invention.</figref><figref num="15A">It is a side view of the trigger mechanism according to another Example of this invention.</figref><figref num="15B">It is a detailed perspective view of the trigger mechanism according to another embodiment of this invention.</figref><figref num="16">It is a perspective view of the trigger mechanism formed according to the other embodiment of this invention.</figref><figref num="17">It is an enlarged perspective view of a part of FIG.</figref><figref num="18">It is an enlarged perspective view of a part of FIG.</figref><figref num="19">It is an enlarged perspective view of a part of FIG.</figref><figref num="20">It is a side view of the trigger mechanism for an actuator according to the embodiment by another method of this invention.</figref><figref num="21">It is a perspective view of the integrated measuring instrument or apparatus which can incorporate the arrangement formed according to this invention.</figref><figref num="22">FIG. 21 is a perspective view of some details of the integrated scale or device of FIG.</figref><figref num="23">It is a perspective view of these parts shown transparently to expose some details built into the integrated scale or device.</figref><figref num="24">FIG. 5 is a perspective view of an alternative embodiment of an integrated device that may include an arrangement formed according to the present invention.</figref><figref num="25">It is a schematic diagram of the optical detection arrangement formed according to one Example of this invention.</figref><figref num="26">It is a schematic diagram of the optical detection arrangement formed according to the Example by another method of this invention.</figref><figref num="27">It is a schematic diagram of the optical detection arrangement formed according to the Example by another method of this invention.</figref><figref num="28">It is a schematic diagram of the optical detection arrangement formed according to another Example of this invention.</figref><figref num="29">It is a schematic diagram of the optical detection arrangement formed according to still another embodiment of this invention.</figref>