CA2469969A1 - Devices, system and methods for extracting bodily fluid and monitoring an analyte therein - Google Patents

Abstract

A system for extracting a bodily fluid sample (e.g., an interstitial fluid [ISF]
sample) and monitoring an analyze therein includes a disposable cartridge and a local controller module. The disposable cartridge includes a sampling module adapted to extract a bodily fluid sample and an analysis module adapted to measure an analyze (e.g., glucose) in the bodily fluid sample. The local controller module is in electronic communication with the disposable cartridge and is adapted to receive and store measurement data from the analysis module. An ISF extraction device includes a penetration member configured for penetrating and residing in a target site of a user's skin layer and, subsequently, extracting an ISF sample therefrom. The device also includes a pressure ring(s) adapted for applying pressure to the user's skin layer in the vicinity of the target site. The device is configured such that the pressure ring(s) is capable of applying pressure in an oscillating manner whereby an ISF glucose lag of the ISF sample extracted by the penetration member is mitigated. A method for extracting ISF includes providing an ISF fluid extraction device with a penetration member and a pressure ring(s). Next, a user's skin layer is contacted by the pressure ring(s) and penetrated by the penetration member. An ISF sample is then extracted from the user's skin layer while pressure is being applied in an oscillating manner by the pressure ring(s). The oscillating pressure mitigates an ISF glucose lag of the extracted ISF sample extracted.

Description

13EVICES9 SYST'El~S A i'~IETI~Il7I~S FC~It EX:~'I~.C~'IN~ Bt,~D~ILY
FI, 11If3NIT~I~l~~ AN ANAT,YTE "I'IEIEItEIN
B.r~C~I~~U ~F' INVEN'fId~N
1. Field of the Invention ~Q001~ 'The present invention relates, in general, to medical devices and their associated methods and, in particu.iar, to devices, systems and methods for extracting bodily fluid and monitoring an analyte therein.

2. Description of the lZelated A.rt (0002 In recent years, efforts in medical devices for monitoring analytes (e.g., glucose) in bodily i~uids (e.g., blood and interstitial fluid) have beea~ directet~.
toward developing devices and methods ~srith reduced user discomfort and/or pain, simplifying monitoring methods and developing devices and methods that allow continuous or semi-continuous monitoring. Simplification ofmonitoring methods enables users to self monitor such analytes at home or in other locations without the help of health care professionals. A reduction in a user's discomfort and/or pain i,~
particularly important in devices and methods designed for home use in order to encourage frequent and regular use. Tt is thought that if a blood glucose monitoring device and associated method are relatively painless, users will monitor their blood glucose levels more frequently and regnzlarly than otherwise.
X0003] In the context of blood glucose monitoring, continuous or semi-continuous monitoring devices and methods are, advantageous in that they provide enhanced insight into blood glucose concentration trends, the effect of food and medication on blood glucose concentration and a user's overall glycemic contral. In practice, however, continuous and semi-continuous monitoring devices ca.n have drawbacks. For example, during extraction of an interstitial. fluid (ISF) sample from a target site (e.g., a target site in a user's skin Iayer), ISF flow rate can decay over time.
Furthermore, after several hours of continuous ISF extractioa~, a user's pain and/or discomfort can increase significantly and persistent blez~ishes can be created at the target site.
[0004 Still needed in the field, therefore, is a device and associated method for the monitoring of an analyte (e.g., glucose) in a bodily fluid such as ISF) that is simple to employ, creates relatively little discomfort and/or pain in a user, and facilitates continuous or semi-continuous monitoring without unduly increasing a user's pain or creating persistent blemishes.
SLT~II~I~' t)F II~~YE:~T'TI~l~
[0005) Systems for the extraction of a bodily fluid sample and monitoring of an analyte therein according to embodiments of the present invention are simple to employ, create relatively little pain and/or discomfort in a user, and facilitate continuous and semi-continuous monitoring without unduly increasing a user's pain or creating persistent blemishes. In addition, ISF extraction devices according to embodiments of the present invention also create relatively little pain and~'or discomfort in a user and facilitate continuous and serxai-continuous monitoring without unduly increasing a user's pain or creating persistent blemishes. lVioreover, methods according to the present invention facilitate continuous or serrai-continuous monitoring without unduly increasing a user's pain or creating persistent blemishes.
00006] A system for extracting a bodily fluid sample and rr~onitoring an analyte therein according to an exemplary embodiment of the present invention includes a disposable cartridge and a local controller module. ~'he disposable cartridge includes a sampling module adapted to extract a b~dily Iluid sample (e.g., an 1SF sample) from a body and an analysis module adapted to measure an analyte for example, glucose) in the bodily fluid sample. In addition, the local controller module is in electronic communication with the disposable cartridge and is adapted to receive and store measurement data (e.g., a current signal) from the analysis module.

[0007] The sampling module of systems according to embodiments of the present invention can optionally includes a penetration member configured for penetrating a target site of a user's skin layer and, subsequently, residing in the user's skin layer and extracting an ISF sample therefrom. The sampling module also optionally includes at Ieast one pressure ring adapted for applying pressure to the user's skin layer in the vicinity of the target site while the penetration member is residing in the user's skin layer, In addition, if desired, the sampling module can be configured such that the pressure a~ing(s) is capable of applying pressure to the user's skin layer in an oscillating manner whereby an ISF glucose lag of the ISF
sample extracted by the penetration member is mitigated.
[OOO~j The disposable nat~rrre of the disposable cartridge renders systems according to the present invention. simple to employ. In addition, when a pressure ring is operated in an oscillating manner according to the present invention, continuous and semi-continuous monitoring is facilitated while simultaneously minimizing a user's pain and the creation of persistent blemishes.
[0009j An interstitial fluid (ISF) extraction device according to an embodiment of the present invention includes a penetration ncamber (e.g., a thin-walled needle with a bore) configured for penetrating a target site of a user's skin Layer and, subsequently, residing in a user's skin layer and extracting an ISF
sample therefrom. The ISF extraction device also includes at least one pressure ring (e.g., three concentrically arranged pressure rings) adapted for applying pressure to the user's skin layer in the vicinity of the target site while the penetration member is residing in the user's skin layer. The ISF extraction device is configured such that the pressure rings) is capable of applying the pressure in an oscillating manner whereby an 1SF glucose lag of the ISl~ sample extracted by the penetration member is mitigated.
[0010] Since the penetration member of ISF extraction devices according to embodiments of the present in vention can reside in a user's skin layer during extraction of an ISF sample, tl~e ISF extraction devices are s;i~nple to employ. In addition, since the ISF extraction device is configured to apply pressure in an oscillating manner, continuous and semi-continuous monitoring is facilitated while minimizing a user's pain and the creation of persistent blemi;>hes.
Application of pressure in an oscillating manner by the pressure rings) can also optimize Mood flow to the vicinity of the target site such that 1SF glucose lag is minimized.
[Q011] ~4 method for extracting interstitial fluid (ISF) according to an en~abodiment of the present invention includes providing an ISF fluid extraction device with a penetration member and at least one pressure ring. I~lext, a user's skin layer is contacted by the pressure ring and penetrated by the penetration member. An ISF
sample is then extracted from the user's skin layer via the penetration member while applying pressure to the user's shin layer in an oscillating manner using the pressure ring(s). The oscillating manner, by which the pressure is applied, serves to mitigate an ISF glucose lag of the ISF sa.~nple extracted by the penetration rnernbei-and/or to facilitate continuous or semi-continuous extraction of an ISF sample for an extended tune period {e.g., an extended tune period in the range of one hour to 24 hours).
~I~IEF DISC PTIfJN ~F ~~'I~GS
[0012] 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 principles of the invention are utilized, and the accompanying drawings of which:
[~C113] FIG. 1 is a simplified block diagram depicting a system for extracting a bodily fluid sample and monitoring an analyte therein according to ara exemplary embodiment of the present invention;
[OOI4] FIG. 2 is a simplified schematic diagram of an ISF sampling module according to an exemplary er;abodiment of the present invention being applied to a user's skin layer, with the dashed arrow indicating a rnechanis~al interaction and the solid arrows indicating ISF llow or, when associated with element 28, the application of pressure;

[0015] FIG. 3 is a simplified block diagram of an analysis module and local controller module according to an exemplary embodiment the present invention;
[001b] FIG. 4 is a simplifZed block diagram of an analysis module, local controller module and remote controller module according tc> an exemplary embodiment of the present invention;
[0017] FIG. 5 is a simplified block diagram of a remote controller module according to an exemplary embodiment of the present invention;
[OOlg] FIG. 6 is a top perspective view of a disposable caz-tridgc and local controller module according to an exez~zplary embodiment of the present invention;
[0019] FIG. 7 is a bottom perspective view of the disposable caztridge and local controller module of FIG. 6;
(0020] FIG. ~ is a perspective view of a system according to another exemplary eznbodirnent of the present invention with the disposable cartridge and local controller module attached to an arm of a user;
[0021] FIG. 9 is a simplified cross-sectional side vie~x~ of an extraction device according to an exemplary embodiment of the present invention;
(0022] FIG. I O is a perspective view of a portion of an extraction device according to yet another exemplary embodiment of the present invention;
[002] FIG. 11 is a simplified cross-sectional side viE;w of the extraction device of FIG. 10;
[0024] FIG. I2 is a graph showing perfusion as a function of time for a test conducted using the extraction device of FIG. 9;
(0025] FIG. 13 is a flow c~iagrain illustrating a sequezace of steps in a process according to one exemplary embodiment of the present invention; and [0026] FIG. 1~1 is a siz~plified cross-sectional side view of a portion of an extraction device according a f~rtl~er embodiment of the present invention.
DETAILEL1 15ES'>>~'IZII''flOl~ L3F ~'IIE II~i~E~T'IG1V
j0027] .A system lU for exaracting a bodily fluid sample ~e.g., an ISF sample) and monitoring an analyte (for example, glucose) therein according to an exemplary embodiment of the present invention includes a disposable cartridge 12 encompassed S

within flee dashed box), a Iocal controller module 14, and a rE.rnote c~antrolier module 16, as illustrated in FIG. 1.
[002g) In system 10, disposable cartridge I2 includes a sampling module 18 for extracting the bodily fluid sample (namely, an ISF sample) from a body (B, f~r example a user's skin layer) and an analysis module 20 for n~uasuring an ar~alyte (i.e., glucose) in the bodily fluid. Sampling module 18 and analysis module 20 can be any suitable sampling and analysis modules known to those of skill in the art.
Fxamples of suitable sampling and analysis modules are described in Inte:national Application hCT/GI301/05634 (International F"ublication Number W~ 02/9507 A1), which is hereby fully incorporated herein by reference. I-Iowever, in system 10, sampling module 18 and analysis module 20 are both configured to be disposable since they are components of disposable cartridge 12.
[0029] As depicted ire FIG. 2, the particular sampling module 18 of system 10 is, however, an ISF sampling module that includes a penetration rnerriber 2'?
for penetrating a target site (TS) of body B anal extracting an ISF sample, a launching mechanism 24 and at least one pressure ring 28. ISF sampling module 18 is adapted to provide a continuous or semi-continuous flow of ISF to analysis module 20 for the monitoring (e.g., concentration measurement) oø' an analyte (:>uch as glucose) in the;
ISF sample.
[0030] During use of system 10, penetration member 22 is inserted into the target site (i.e., penetrates the target si3:e) by operation of launching mechanism 24.
For the extraction of an ISF sarrpl.e from a user's skin layer, penetration member 22 can be inserted to a maximurrn insertion depth in the range of,, for example, 1.5 mrr~, to 3 mm. In addition, penetration member 22 can be configured to optimize extraction of an ISF sample in a continuaus or semi-continuous manner. In this regard, penetration member 22 can include, for example, a 25 gauge, thin-wall stainless stee needle (not shown in FIGS. 1 or 2) with a bent tip, wherein a fa~lcrum for the tip bend is disposed between the needle's tip and the needle's heel. Suitable needles for use in penetration members according to the present invention are described in U.S.
Patent Application Publication US 20Q3/006(3784 A1 (Application IVo. 1/185,605).
[OO~IJ Launching mechanism 24 can optionally include a hub (not shown in FIf'rs. 1 or 2) surrounding penetration member 22. Such a hub is configured to control the insertion depth of penetration member 22 into the target site. Insertion depth control can be beneficial during the extraction of an ISF sample by preventing inadvertent lancing of blood capillaries, which are located relatively deep in a user's skin layer, and thereby eliminating a resultant fouling of an extracted ISF
sample, clogging of the penetration f~ember or clogging of an analysis module by blood.
Controlling insertion depth c,an also serve to minimize pain and/or discom~~°ort experienced by a user during use of system 10.
[00~2J Although FICi. 2 depicts launching mechanism 24 as being included in sampling module 18, launching ~nc;chanism 24 can optionally be included ire disposable carsridge 12 or in local controller module 14 of system 10.
Furthermore, to simplify employment of system l fl by a user, sampling module 1 ~ can be fovrmed as an integral part of the analysis ~nod~zls~ 20.
~0033J In order to facilitate the extraction. of a bodily fluid (e.g., ISF) from the target site, penetration member 2 2 can be arranged concentrically within at least one pressure ring 28. Pressure rings) 28 can be of aa~y suitable shape, including but not limited to, annular. In addition, pressure rings) 28 can be conlagured to apply an oscillating mechanical force (i.e., pressure) in the vicinity of the target site while the penetration member is residing in the user's skin layer. Such oscillation can be achieved through the use of a biasing element (not shown in FICrs. 1 or 2), such as a spring or a retention block. The structure and function of a pressure rings) in sampling modules (and ISF extraction devices) according to the present invention are described in more detail below with respect to FIC'rs. 9-12.
~0034J wring use of system 10, pressure ring 28 is applied in the vicinity of the target site ~'S, prior to penetration of the target site by penetration member 22, in order to tension the user's skin layer. Such tension servca to stabilize the user's skin layer and prevent tenting thereof' during penetration by the pen etrating member.
A.lternativeiy, stabilization of the user's skin layer prior to pen etration by the penetrating member can be achieved by a penetration depth control element (not shown) included in sampling module 18. Such a penetration depth control element rests or "floats" on the surface of the user's skin layer, and acts as a limner for controlling penetration depth (also refeared to as insertion depth). Examples of penetration depth control elements and tlmir use are described! in LJ.S, patent ' application Serial No. 10/-~ [attorney docket ~o. LFS-5002], which. is hereby fully incorporated r~erein by reference. If desired, the penetration member can be launched coincidentally witl-~ application of the pressure rings) to the user's skin Layer, thereby enabling a simplification of the launching mechanism.
[0035] Gnce penetration member 22 has been launched and has penetrated the target site 'I'S, a needle (not shown in FIGS. 1 or 2) of penetration member 2,2 will reside, for example, at an insertion depth in the range of about 1,5 mim to '~
mm below the surface of the user's skin layer at the target site. The pressure rings) applies/apply a farce on the user's skin layer (indicated by the downward pointing arrows of FIG. 2) that pressurizes ISF in the vicinity of the target site. A
sub-dermal pressure gradient induced by the pressure rings) 28 results/result in flow of ISF up the needle and through the sampling module to the analysis mode le (as indicated by the curved and upward pointing arrows of FIG. 2).
~003b) ISF flow through a penetration member's needle i.s subject to potential decay over time due to depletion of ISF near the target site and due to relaxation of the gasser's skin layer under the pressure rings) 28. however, in systems according to the present invention, pressure rings) 28 can be applied to the us~rx-'s skin layer in an oscillating manner (e.g., with a predetermined pressure ring(s;) cycling routine or with a pressure ring cycling routine that is controlled via ISF flow r ate measurement and feedback) while the penetration member is residing in the user's skin layer in order to minimize ISF flow decay. In addition, during application of pressure in an oscillating manner, there can be time periods during which the pressure applied by the pressure rings) is varied or the local pressure gradient is removed and the net outflow of ISF
from the user's skin layer is eliminated.
[0037] Furthermore, alternating the application of a plurality of pressure rings to the user's skin layer in the vicinity of the target site c.an sers~e to control the flow of ISF through the sampling and analysis modules and limit the time that any given portion of the user's skin layer is under pressure. By allowing a user's skin.
layer to recover, the application of pressure in an oscillating manner also reduces blemishes on the user's skin and a user's pain and/or discomfort. An additional beneficial effect of applying pressure rings) 28 in an oscillating manner is that ISF glucose lag (i.e., the difference between glucose concentration in a user's ISF and glucose concentration in a user's blood) is reduced.
[0038] ~nce apprised of the present disclosure, one skilled in the art can devise a variety of pressure ring cycling routines that serve to reduce ISF
glucose lag, a user's pain/discomfort andlor the; creation of persistent skin ~lernishes.
For example, the pressure rings) 28 can be deployed (i.e., positio ed such that pressure is applied to a user's skin layer in the vicinity of a target site} for a period of from 3D
seconds to 3 hours and can then be retracted (i.e., positioned such that pressure is not being applied to the user's skin layer) for a period ranging from 30 seconds to 3 hours.
Moreover, it has been determined that ISF glucose lag and a user's pain/discomfort are significantly reduced when the amount of time during which pressure is applied (i.c., the time period during which at least one pressure ring is deployed} is in the range of about 30 seconds to about 10 minutes and the ar~aount of time during which pressure is released (i.e., the time period during which the at least one pressure ring is retracted) is in the range of about 5 minutes to 10 minutes. f~ particularly beneficial pressure ring cycle includes the application of pressure for one minute and the release of pressure for 1 D minutes. Since different amounts of tune are used for applying and releasing pressure, such a cycle is referred to as an asymmetric pressure ring cycle.
[0039] Pressure ring cycling routines can be devised such that the following concerns are balanced: (i) having the pressure rings) deployed for a time period that is sufficient to extract a desired volume of bodil;, fluid, (ii) iraucing a physiological response that mitigates ISF glucose lag, and (iii) minimizing user discomfort and the creation of persistent blemishes. In addition, pressure ring cyeling routines can also be devised to provide for semi-continuous analyte measurements that occur, for example, every 15 minutes.
[0040] Fressure rang(s) 28 can be formed of any suitable material known to those of skill in the art. For exarn;ple, the pressure rings) 28 can be composed of a.
relatively rigid material, including, but not limited to, acrylonitrile butadiene styrene plastic material, injection moldable plastic material, polystyrene material, metal or combinations thereof. The p~-essu~re ring{s) 28 can also be composed of relatively resiliently deformable material, including, but not limited to, elastomeric materials, polymeric materials, polyurethane matcrials, latex materials, ;silicone materials or combinations thereof.
[0041] tin interior opening defined by the pressure rings) 28 can be in any suitable shape, including but not limited to, circular, square, triangular, ~-shape, U-shape, hexagonal, octagonal and crenellated shape.
[0042] ~Jhen pressure ring>{s) 28 is being employed to~ minimise 1SF~ flow decay andlor control the flow of ISF through the sampling and analysis modules, penetration member 22 remains deployed in (i.e., residing in) the target site of the user's skin layer while the pressure rings) 28 is/are in use. I-Iowever, when pressure rings) 28 are being employed to mitigate ISF glucose lag, the penetration member 22 can intermittently reside in the raser's skin layer. Such intermitte~xt residence of the penetration member 22 can occur either in or out of concert with the application of pressure by the pressure rings) 28.
[0043] Refernng to Fib. 3, analysis module 20 of system 10 includes a distribution ring 302, a plurality of~micro-t~luidic networks 30~~ and a plurality of electrical contacts 306. Each of micro-ftuidic networks 302 includes a first passive valve 308, a glucose sensor 3108 a waste reservoir 312, a second passive valve and a relief valve 316. Micro-fluid networks 304 include channels with a cross-sectional dimension in the range of, for example, 30 to X00 micrometers. For monitoring (e.g., measuring) gluc,c~se in a flowing ISF sample, a plurality (n) of essentially identical micro-fluidic :networks 304 (also referred to as sensor branches 304) can be included in analysis rrnodule 20. Distribution ring 302, first passive valve 308, waste reservoir 312, second passive valve 314 and a relief valve 315 are configured to control ISF flow through anailysis module 2(l.
[0044] ~lny suitable gluco.ce sensor known to those of'skill in the art can be employed in analysis modules according to the present invention. C3Iucose sensor 310 can contain, for example, a redox reagent system including an. enzyme and a redox active compounds) or mediator(s). A variety of different mediators are known in the art, such as ferricyanide, phenazine ethosulphate, phenazine methosulfate, pheylenediamirie, 1-methoxy-phenazine methosulfate, 2,6-dirnzethyl-l,4-benzoquinone, 2,5-dichloro-1,4-be;nzoquinone, ferrocene derivatives, osmium bipyridyl complexes, and rutheniu~rrE complexes. Suitable enzymes for tl~e assay of glucose in whole blood include, but are not limited to, glucose oxidase and dehydrogenase (both NAD and I~QQ based). Other substances that may be present in the redox reagent system include buffering agents (e.g., citraconate, citrate, rnalic, malefic, and phosphate buffers),° divalent canons (e.g., calcium chloride, and magnesium chloride); surfactants (e.g., Triton, li~acol, Tetroni.c:, Silwet, ~onyl, and Platonic); and stabilizing agents (e.g., albumin, sucrose, trehalose, mannitol and lactose).
[0045] In the circumstance that glucose sensor 310 is a~~ electro-chemical based glucose sensor, glucose sensor 310 can produce an electrical current signal in response to the presence of glucose in an ISF sample. Local controller module 14 can then receive the electrical current signal (via electrical contacts 30t) and cordvert it into ISF glucose concentration.
]0046] System 10 can be employed for the continuous and/or semi-continuous measurement (monitoring) of glucose in an ISF sample for a period of eight hours or more. I-iowever, conventional glucose sensors that can be economically ma.ss-produced provide an accurate measurement signal for a lifetirr~e of only about one hour. In order to overcome this problem of limited sensor lifetime, a plurality of micro-fluid networks 304, each containing an identical gluco sP sensor 31.0, are provided in analysis module 20. Each of these glucose sensors is employed in a consecutive manner to provide continuous and/or semi-continuous monitoring for a period of more than ~ne hour.
[004'7] The consecutive usE; of identical glucose sensors (each for a limited period of time, such as one hour) enables a. continuous or sem.i.-continuous measurement of glucose. 'The consecutive use of identical glucose sensors can be implemented by guiding an incoming flow of ISF from a sampling module towards a glucose sensor 310 for a period of time, followed by interrupting the ISF flow to that glucose sensor and switching the ISF flow to another glucose sensor. This consecutive use of glucose sensors can be repeated until each glucose sensor included in an analysis module has been ~.se;d.
[0048] '.E hhe switching of the ISF flaw to consecutive gla~cose sensors can be accomplished, for example, by the following procedure. Upon initialization of analysis module 20, an ISF sample from sampling module 18 is distributed via distribution ring 302 to "n" sensor branches 304. However, the flow of ISF is halted at an inlet end of each sensor bra.nc;h by the first passive valve 308 of each sensor branch. To start the measurement of glucose, a selected sensor branch is activated by opening the relief valve 316 of that sensor branch. 'The process of opening a selected relief valve can be electrically controlled by local controller module I4, which communicates with analysis module 20 via electrical contacts 306. Upon opening of a relief valve 316, gas (e.g., air) that is initially present in the sensor branch 304 (which is hermetically sealed) escapes ar an outlet end of' the sensor branch 304, and, as a result, ISF will flow into that sensor branch 304. As the relief valves 316 of the other sensor branches 304 remain closed., the ISF is allowed to flow only into the selected sensor branch 304.

[0049) The pressure of the ISF is sufficiently large to breach first passive valve 308 and will, therefore, flow towards glucose sensor 310. A measurement signal is subsequently created by glucose sensor 310 and communicated electronically via electrical contacts 306 to the local controller module 14 (as depicted by the dashed arrows in FI(3. 3). ISF continues fJ.owing and enters waste reservoir 312, the volurme of which is predetermined such fta.t it can contain an amount a~f ISF
equivalent to that needed through the glucose sensor"s lifetime. For example, at the average f7.ow rate of about 50 nanoliters per minute and a glucose sensor lifetime of one hour, the volume of waste reservoir 312 would be approximately 3 microliters. ~ second passive valve 314 is located at the end of the waste reservoir 3 I2. The second passive valve 3 I4 is configured to stop the flow of ISF.
[0050] The procedure then continues by opening of a relief valve 316 of another sensor branch 304. Upon selectively opening this relief valve 31~
{which can be accomplished via communication by the local controller module 14), ISF will flow into the corresponding sensor branch 304 after breaching the first passive valve 308 located in that sensor branch. Thereafter, the glucose sensor 310 of that sensor branch will provide a measurement signal to analysis module 20.
[0051] This procedure is repeated until all sensor branches 304 of analysis module 20 have been used. For a system to provide about eight hours of continuous glucose monitoring, about eight sensor branches 304 will be required in analysis module 20. It will be appreciated by those skilled in the art, however, that the analysis module 20 of disposable cartridge 12 is not limited to eight sensor branches and that, therefore. the system can be designed to measure ISF glucose levels for longer (or even shorter) than eight hours.
[0052] Local controller module 14 is depicted in simplified block form in FICI

4. Local controller module 14 includes a mechanical controller 402, a first electronic controller 404, a first data display 406, a local controller algorithm 408, a first data storage element 410 and a first RF link 412.
l '~

[OOS3j Local controller ra~odule 14 is configured such that it can be electrically and mechanically coupled to disposable cartridge 12. 'fhe mechanical coupling provides for disposable cartridge 12 to be reanovably attached to (e.g., inserted int~) local controller module 14. Local controller module 14 and disposable cartz-idge I1 are configured such that they carp be attached to the skirg of a user by, for example, a strap, in a manner which secures the combinatior~~ of the disposable cartridge 12 and local controller module 14 onto thsv user's skin.
[0054] ~uu~-ing use of system 10, first electronic controller 404 controls the measurement cycle of the analysis module 20, as described above.
Gonarnunication between local controller rnociule 1 ~l and disposable cartridge 13 takes place via electrical contacts 306 of analysis module 20 (see FIG. 3). Elc;ctrical contacts 306 can be contacted by contact pins i08 (see FIG. 7) of the local contrs~ller module 14.
Electrical signals are sent by the local controller nodule 14 to analysis module ZO to, for exarraple, selectively open relief valves 316. Electrical signals representing the glucose concentration of an ISF sample are then sent by the analysis module to the local controller module. First elecl:ronic controller 404 interprets these signals by using the local controller algorithrr~ 408 and displays measurement data on a first data display 406 (which is readable by the user). In addition, rraeas~.~rernent data (e.g., I~:~F
glucose concentration data) can be stored in first data storage ~;ler~-aent 409.
[0055] Prior to use, an unu:~ed disposable cartridge I2 is inserted into local controller module 14. This insertic'n provides for electrical co~rckmunication between disposable cartridge 12 and local controller Hnodule 14. ~ mechanical controller 40:2 in the local controller module 14 securely holds tl-xe disposable cartridge 1~
~n place during use of system 10.
[0056] After attachrr~ent of a local controller module aru disposable cartridge combination to the skin of the user, and upon receiving an activation signal from the user, a measurement cycle is initiated by first electronic controlh:r 404.
Clpon such initiation, penetration member 22 i;9 launched into the user's skim layer to start ISF

sampling. The launching can be initiated either by first electronic controller 404 or by mechanical interaction by the user.
[OOS7j First IZF link 412 of local controller module I4 is configured to provide bi-directional communication bet~v~ecn the local controller module and a rerrzote controller module 16, as depicted by the jagged arrows ofFIGs. 1 and 4. The local controller module incorporates a visual indicator (e.g., a multicolor L~I3) indicating the current status of the system.
[0058j Local controller module 14 is configured to receive and store measurement data from, and to interactively communicate with, disposable cartridge 12. For example, local controller module 14 can be configerred to convert a measurement signal from analysis nnodule 20 into an ISF or blood glucose concentration value.
[0059) FIG. 5 shows a simplified block diagram depie~ting remote controller module 16 of system 10. Remote controller module 16 includes a second electronic controller 502, a second RF link 504, a second data storage element 506, a second data display 508, a predictive algorithm 510, an alarm 512, a blood glucose measurement system (adapted t~ measure blood glucose utilizing blood glucose strip S16) and a data carrying element 5'.IB.
[0060] Second electronic controller 502 is adapted to control various components of remote controller module 16. Second RF link 504 is conf gored for bi-directional communication with the Local controller module 14 (e.g., second R.F Link 504 can receive ISF glucose concentrati~n related data from Local controller module 14). Data received via second lie link 504 can be validated arrd verified by second electronic controller 502. Furthermore, the data so received carr also be processed and analyzed by second electronic controller 502 and stored in second data storage element 506 for future use (e.g., future data retrieval by a user or for use in predictive algorithm 510). Second data display 508 ofremote controller ~modulc 16 Call be, for example, a graphic LCD display configured to present :neasurerncnt data in a convenient format to a user and to present an easy to use interface for further data management.
(0061] The local controller module I4 is adapted to comrraunicate via second DF link 5~4 to a remote controller module I6. Functions of remote controller module I6 include the displaying, storing and processing of glucose measurement data in a presentable and convenient formavt for the user. Demote contr~Iler module I6 can also provide an (audible, visual and/or vibratory) alarm via alarm S I Z for warning the user of deleterious glucose concentrations. A further function of remote controller module I6 is to measure a user's blood ghacose concentration using blood glucose measurement system 514 and a single use blood glucose measurement strip S 16.
Blood glucose values measured by blood glucose measurement system 514 can be used to verify blood glucose values calculated by predictive augorithrn 51 ~.
Demote controller module I6 can also be configured to provide for user specific data (e.g., event tags, state of mind and medical data) to be entered and parsed.
[0062) Remote controller module 16 is configured as a portable unit and to communicate with local controller module 14 (e.g., to neceivirg glucose measurement data from local controller module I4). Demote controller module I6, therefore, provides a user with a simple and convenient platform for managing glucose monitoring-related data (e.g., stoning, displaying and processing of glucose monitoring-related data) and can be used to fine tune therapy (i.e., insulin administration). Functions of the remote controller module 1 b can include the gathering, storing and processing of I~F glucose data and the display of the blood glucose value calc~zlated from ISy glucose data. By incorporating such functions in remote controller module 16, rattrer than local controller modals I4, the size and complexity of Local controller nncedule I4 are reduced. However, if desired, the remote controller module functions described above can be alternatively performed by the local controller module.

[0063] In order to facilitate a measurement of the blood glucose Ieve1 m a blood sample (ES), blood glucose measurement system 514 i.s provided as an integral part of the remote controller module 16. The blood glucose measurement system makes a meas~xren~ent with a blot>d glucose strip S I6, on which a blood sample (e.g., a drop of blood) has been placed. The resulting blood glucose measurement can be compared to glucose values calculated by predictive algorithm S 1I,'.
[0064] Remote controller rr~odule I 6 can optionally incorpo~°ate a communication port, such as a serial communication port (not shown in FIG. 5).
Suitable communication ports are known in the art, for example, an RS23~ (IEEE
standard) and a Universal Serial I3us. Such communication ports can be readily adopted for exporting stored data to an external data management system.
Remote controller module I 6 also incorporates a programmable memory portion (mot shown in T'IG. 5), such as a reprograrrLSnabIe flash memory portion, that can be programmed via a communication port. A purpose of such a memory portion is to facilitate updates of an operating system and/or other software element of the reyraote controller module via communication through the corrnnunication part.
[0065) The remote controller module I6 can further include a con.~rnunication slot (not shown) for receiving a data carrying element 518 and communicating therewith. data carrying element S I8 can be any suitable data carrying element known in the art, such as a 'SIh~' data carrying element, also known as "smart-clasp."
[0066) T3ata carrying element S I 8 can be provided with a disposable cartridge 12 and can contain disposable e~arty-idge production lot specific data, such as calibration data and Iot identification number. 'The remote controller module 16 can read the data contained on data. carrying element S I8 and such data can be employed in the interpretation ofthe ISIF glucose data received from the local controller module 14. Alternatively, the data on data carrying element 5 I8 can be communicated to the local controller module 14 via second RF link 504 and can be used in data analysis performed by the local controller module I4.
1 ~r [0067] 'fhe second electronic controller 502 of remote; controller module I 6 is configured to interpret data, as yell as to perform various algorithms. ~ne particular algorithm is predictive algoritt~rn 510 for predicting near future (within 0.5-I hour) glucose levels. As there is a time difference ("lag time") between changes of glucose concentration in the blood of the user and the corresponding change of glucose concentration in the ISF of the user, predictive algorithm 5 I O uses a series of mathematical operations perforanea3 on the stored measurement data to take into account user specific parameters reelecting ~ndgvldual lag time relationships.
The outcome of the predictive al~orithrn 510 is an estimation of the blood glucose level based on the ISF glucose level. If the predictive algorithm 5 i 0 predicts low glucose levels, a signal can be raised and alarm S I ~ activated to warn the user of a predicted physiological event such as hypoglycemia or risk of corraa. As will be appreciated by those skilled in the art, the alarm S I2 may be comprised of any suitable signal including an audible, visual or vibratory signal, warning either the user directly or the user's health care provider. An audible signal is preferred, as it will wake up a sleeping user encountering a hypoglyce~~nic event.
[006g] Tlae difference between an ISF glucose value (concentration) at any given moment in time and a blood glucose value (concentration) at the same moment in time is referred to as the ISF glucose Iag. ISF glucose lag ~;an be conceivably attributed to both physiological and mechanical sources. ~'he physiological source of lag in ISF glucose is related to tl3e time it takes for glucose to diffuse between the blood and interstices of a user's skin layer. The mechanical source of lag is related to the method and device used to obtain an ISF sample.
[0069] Embodiments of devices, systems and methods according to the present invention mitigate (reduce or minimize) ISF glucose lag due to physiological sources by applying and releasing pressure to a user's skin layer in an oscillating manner that enhances blood flow to a target area of the user's skin layer. ISF
extraction devices that include pressure rings) according to the present invention (as described in detail below) apply and release pressure in this manner. Another approach to account for lag in ISF glucose is to employ an algorithm (e.g., predictive algorithm 510) that predicts blood glucose concentration based on measured ISF
glucose concentrations.
[007a~ Predictive algo:°ithrn 51 (3 can, for c;xarnple, tal~~~ the general form:
Predicted blood glucose = f(ISF';~9 rate, rnanraternr, interaction terms) where:
i is an integer of value between ~ and 3;
j, n, and m are integers of value between l and 3;
k and p are integers of value 1 or 2;
ISF, is a rneas~red ISF glucose value with the subscript (ij indicating which ISIS value is being referred to, i.e., 0 = current value, 1 = one value back, 2 =
two values back, etc.;
rated as the rate of change aetween adjacent ISf values with the subscript (i) referring to which adjacent ISF values are used to calculate the rate, i.e., 1 = rate between current ISF value and the previous ISF value,1= rate between the ISp' values one previous and two previous relative to the current I SF value, etc.;
and ma"ratem is the moving average rate between adjacent averages of groupings of ISF values, with the, subscripts (n) and (m) referring to (n) the number of ISF values included in the moving average and (rn) the time position of the moving adjacent average values relative to the current values as follows.
[01771) The general form ofthe predictive algorithm is.a linear combination of all allowed terms and possible cross terms, with coefficients fir the terms atad cross terms determined through regressian analysis ofrneasured ISF values and blood glucose values at the time of the ISF sample acquisition. Further details regarding predictive algorithms suitable for use in systems according to the present invention are included in U.S. Patent Application I~io. (Attorney U~ochet I~lo. L.FS-50(3',0, which is hereby incorporated by reference.
[00'72] As will also be appreciated by those skilled in the art, the outcome of the predictive algorithm can be used to control medical devices such as insulin delivery puynps. A typical example of a parameter that can be determined based on the algorithm outcome is the voluyne of a bolus of insulin to be ad~ni~aistered to a user at a particular point in time.
[0073] T'he combination of local controller module 14 and disposable cartridge 12 can be configured to be worn on the skin of a user in ~rder to simplify sampling and monitoring of ISF e;~tracted from the user's skin layer (see F'I~s. 6-8).
[0074] ~uring use of the system embodiment of FI~s. 1-10, disposable cartridge 12 is located within and controlled by local controller module 14.
In addition, the combination of disposable cartridge 12 and local controller module I4 is configured to be worn by a user, preferably on the upper part of the user's arm or forearm. '.Che local controller nodule I4 is in electrical communication with the disposable cartridge I2 for purposes of measurement control and for receiving measurement data from the analysis module.
[0075] Referring to FIB. 6, local controller module 14 includes a first data display 406 and a pail of straps 602 for attachment of the local controllea~
module 14 to the arm of a user. FIB. f~ also depicts disposable cartridge I2 prior to insertion into local controller module I4.
[0076] fICp. 7 shows a bottom view of the local controller module 14 prior to the insertion of the disposable cam~idge 12 into an insertion cay~ity 704 provided in local controller module I4. The disposable cartridge 12 and local controller module 14 are configured such that disposable cartridge 12 is secured within the insertion cavity 704 by mechanical force. In addition, the local controller module 14 and the disposable cartridge I2 are in electrical communication via a set ofmolded contact pads 70b that are provided on disposable cartridge I2. These molded contact pads 706 are in registration with a set of contact pins 708 provided within the insertion cavity 704 of the local controller module I4 when the disposaEble cartridge is inserted into insertion cavity 704.

[0077] FiG. 8 shows the lo~~al controller module 14 after insertion of the disposable cartridge 12 into local controllcr module 14 and attachment of the combination of the disposable cartridge and local controller module onto the arm of ~
user. FIG. 8 also depicts a remote controller module 16 located within I~F' communication range of the local controller module 14.
[0078] FIG. 9 is a cross-sectional side view of an interstitial fluid (ISF) extraction device 900 according to an exemplary embodiar~ent: of the present invention. ISF extraction device 900 includes a penetration rrrernber 902, a pressure ring 904, a farst biasing member 9f~ (i.e., a first spring) and a second biasing member 908 (namely, a second spring).
j00°79] Penetration member 902 is configured for penE;tration of a user's skin layer at a target site and for the subsequent extraction of ISF therefrom.
Penetration member 902 is also configured to remain ire (reside in) the use;r's skin layer during i;he extraction of ISF therefrom. penetration member 902 can, for example, remain in the user's skin layer for more than one hour, thus allowing a cont:ia~uous or serni-continuous extraction of ISF. Gnce apprised of the present disclosure, one skilled in the art will recognize that the penetration member can reside i.n the user's skin layer for an extended period of time dn'' 8 hours or more.
[0080] Pressure ring 904 is configured to oscillate between a deployed state and a retracted .state. When pressure ring 904 is in the deployed state, it applies pressure to the user's skin layer smrrounding the target site, wlliIe the penetration member is residing in the use.r's skin layer in order to (i) facil:itate the extraction of ISF from the user's skin layer and (ii) control the flow of ISF through ISF
extraction device 900 to, for example, an analysis module as described above. When pressure ring 904 is in a retracted state, it applies either a minimal pressure or no pressure to the user's skin Layer surrounding the target site. Since pressure ring 904 can be oscillated between a deployed state: and a retracted state, the time that any gimen portion of a user's skin layer i s under pressure can be controlled, thereby providing for the user's skin layer to reoover andl reducing pain and blemishes.

[0081] Pressure ring 904 typically has, for exarr°aple, an outside diameter in the range of 0.08 inches to 0.5f~ inches and a wall thickness (depicted as dimension "~" in FI~i. 9) in the range of 0.02 inclfes to 0.04 inches [0082] First biasing element 90b is configured to urge pressure ring 904 against the user's skin layer {i.e., to place pressure ring 904 into a deployed state) and to retract pressure ring 904. Second biasing element 90S is configured to lau.~ach the penetration member 902 such that the penetration member penetrates the target site.
[0083] The pressure {force] applied against a user's shin layer by tile pressure ring(sj can be, for example, in the range of from about 1 to 1.'>0 pounds per square inch (PSI, calculated as force per c~rosswsectional pressure ring area). In this regard, a pressure of approximately 50 PST has been deterallined to be lzeneficial with respect to providing adequate ISF $low while minimizing user pain/discorofort.
(0084] In the embodiment of FIG. 9, penetratiorf mergner 902 is partially housed in a recess of the oscillating pressure ring 904, the deJ~th of the recess determining the maximum penetration depth of the penetration member 902.
Although not explicitly shovrn ire :FIG. 9, the penetration member 902 and t;he oscillating pressure ring 904 can be moved relative to one,ana~ther and applied to a user's skin layer independent of each other.
(0085] During use of ISF extraction device 900, the oscillating pressure ring 904 can be deployed for stabilizing the user's skin layer and to isolate and pressurize a region of the target area and thus t:o provide a net positive pressure t~
pror~aote flow of ISF through penetration member 902.
[0086] If desired, ISF extraction device 900 can eontain a penetration depth control element (not shown) for limiting and controlling the depth of needlf:
penetration during lancing. l~xamples of suitable penetration depth control elements and their use are described in I1.S. patent application Serial t~Io.

~Attomey Docket No. LFS-500?_~, which is hereby fully incorporated herein by reference.
(0087] During use of ISF extraction device 900, a system that includes ISF
extraction device 900 is placed against a user's skin layer with the pressure ring 904 facing the skin (see, for example, FIG. 8). The pressure ring 904 is urged against the skin to create a bulge. The bulge is then penetrated (e.g., lanced) by the penetration member 902. An ISF sample is subse~uentiy extracted from the bulge while the penetration member 902 remains totally or partially within the skin.
[0088] The flow rate of the ISF sample being extracted is initially relatively high but typically declines over time. After a period in the range of ~
seconds to ~
hours, pressure ring 904 can he retracted to allow the skin to recover for a period of about 3 seconds to 3 hours. 1'ressvre ring 904 can then be re-deployed for a~
period in the range of about 3 seconds to about 3 hours and retracted for about 3 seconds to 3 hours. This process of deploying and retracting pressure ring; 904 proceeds until ISF
extraction is discontinued. The deployment and retraction cycles are preferably asymmetric in that different periods oi' tune are used for each cycle.
X0089] FIGS. 10 and 11 are cross sectional and perspective views, respectively, of an ISF extraction device 9S0 according to another exemplary ernbodirnent of the present invention. ISF extraction device 950 includes a penetration member 952 and a plurality of concentrically arranged pressure rings 954, 9548 and 954C. ISF
extraction device 950 also includes a plurality of first biasing elements 956A, 9568 and 9560 fox urging the pressure rings 954A, 9S4B and 9560, respectively, toward and against a user's skin layer, a second biasing element 958 for launching the penetration member 952, and a penetration depth control element 960.
X0090] During use, ISF extraction device 950 is positioned such that pressure rings 9S4A, 954B and 954C are facing a user's skin layer. This can be accomplished, for example, by employing ISF extraction device 950 in a sampling module of a 2~

system for extracting bodily fluid as described above and placing the system against the user's skin layer.
[0098] Pressure ring 954A is then urged against the user's skin layer by biasing element 956A, thereby creating a bulge Pn the user's skin layer that gill subsequently be lanced ~i.e., penenrated) by penetration rnemtrer 952. While pressure ring 954A is in use ~i.e., deployed), pressuie ring 954B and pressure ring 954C can be maintained in a retracted position by biasing elements 956B and 956t,, respectively.
[0092) ISF can be extracted from the bulge forrr~ed in user's skin layer while the penetration lnember 952 resides totally or partially within flee user's skin Layer.
After about 3 seconds to 3 hours, the pressure ring 954A can be retracted to allow the user's skin layer to recover for a time period in the range of abcaut 3 seconds to 3 hours. After retracting the pressure ring 954A, pressure ring 954B can be deployed to apply pressure on the user's skin layer. VV~ile pressure ring 954B is an use (:i.e., deployed), pressure ring 954A and pressure ring 954C can be maintained in a retracted position by biasing elements 95bA and 9560, respectively. After a time period of about 3 seconds to 3 hours, pressure ring 9548 can be retracted for a time period in the range of 3 seconds to 3 hours, followed by the deployment of pressure ring 9540.
Pressure ring 9540 maintains pressure on the user's skin layer ror a time period in the range of 3 seconds to 3 hours and is then retracted for a time period in the range of 3 seconds to 3 hours. While pressure ring 9540 is in use (i.e., deployed), pressure ring 954A and pressure ring 954B can be maintained in a retracted position by biasing elements 956A and 956B, respectively. This process of cycling between deployment and retraction of pressure rings 954A, 954B anal 954C can pr~~ceeds until fluid extraction has ended. As with the embodiment shown in FIG. 9, the deployment and retraction cycles in the multiple pressure ring embodiment of lFnGs. 1 Q and 11 are preferably asymmetric in that different periods of time are used for each cycle.
[0093] Those skilled in the art will also recognize that a plurality of pressure rings in ISF extraction devices according to the present invention can be deployed in any order and that one is not Limited to the deployment and retraction sequence described above. For example, a sequence can be used in which pressure ring 954B or 9540 is applied before pressure ring 954th. Further, more than one pressure ring can be deployed simultaneously. For e;xarnple, the embodiment sll~~'wn in FIGS. 10 and 11 can deploy alI three pressure rings sirnt~ltaneousl~;~ such that the pressure rings function as a single pressure ring.
(0094] For the embodiment shown in FIGs. 10 and 11, the pressure applied against the user's skin can, for example, range from about 0.1 to 150 pounds per square inch (1'Sl) for each of the foiurality of pressure rings.
(0095] T he pressure rings 9541, 954B and 954; can have, for example, outer diameters of in the range of 0.08 to 0.560 inches, 0.1 to 0.9 inches and 0.16 to 0.96 inches, respectively. The wall thickness of each pressure ring can be, for example, in the range of 0.02 to 0.04 inches.
(0096] An inner-most pres;~ure ring of extraction devises according to an alternative embodiment of the present invention can, if desired, be a flat ring (see FIG.
140 for the purpose of keeping tl~e needle in the user's skin layer while applying negligible pressure to keep blood flowing to the area. FIG. 14 shows a cross-sectional side view of a portion of an interstitial fluid (ISF) extraction device 970 according to an alternative exemplary embodiment ofthe present invention. 15:~ extra.ction device 970 includes a penetration member 972% a pressure ring 974, a. flat pressure ring 975, a first biasing member 976 (i.e., a first spring) for biasing the pressure ring 974 and a second biasing member 978 (namely, a second spring) for bia;>ing the flat pressure ring. .
]0097] In this alternate emi~odin~cnt, the flat pressure ring surrounds the needle (i.e., the penetration ~nembe,r 972) and contains a hole of sufficient size to just allow the needle to pass through. The flat pressure ring preferably has a diameter of 0.02 to 0.56 inches.

(0098] Inclusion of at least one pressure ring in extraction devices according to the present invention provides a number of°benefits. First, oscillating tile pressure rings) between a deployed and retracted state serves to mitigate (i.e., reduce) ISF
glucose lag. Ll~pon retraction of the pressure ring(s), pressure on the user's skin layer is released, and the user's body reacts by increasing blood perfusion to the target site.
'his phenomenon is known as reactive hyperemia and is hypothesized to be a mechanism by which ISF is beneficially replenished in the target site by oscillation of the pressure ring(s)° Such a replenishment of ISF helps mitigating the lag between the ISF glucose and whole blood glucose values.
(0099] Another benEfit of ISF extraction devices according to the present invention is that oscillation of the pressure rings) allows the s kin under the pressure rings) to recover, thus reducing a user's pain, discomfort and the creation of persistent blemishes.
(00100] Moreover, extraction devices with a plurality of pressure rings {e.g., the embodiment of FIGis. 10 and 1 l;~ can be used with at least one pressure ring permanently deployed to facilitate iSF collection while the other pressure rings are oscillated between deployed and retracted states so that differE;nt areas of tlae user's skin layer are under pressure at any given time. Such combination of permanently deployed pressure rings) and osci:(lated pressure rings) further aids in reducing a user's pain/discomfort.
(00101] Still another benefit of ISF extraction devices according to the present embodiment is that the pressure rings) can be used to control the conditions under which a glucose measurement of an extracted ISF sample is conducted. For example, an electrochemical glucose sensor is more accurate and precise if the ISF
sample flow rate past the glucose sensor is constant or static. 'fihe pressure rings) of ISF extraction devices according to the present invention can provide a controlled flow of the extracted ISF sample. For example, retraction of the pressure rings) can stop ISF
sample floau for a time period of t?, l seconds to 6~ minutes to a3.low a glucose concentration measurement to b;,d conducted. Once the glucose concentration measurement is complete, one or more of the pressure rings c:~n be redeployed to continue ISF extraction. In this rrtanner, a serr~i-continuous ISF sample extraction can be accomplished.
[00102] ~nce apprised of the present disclosure, one skilled in the art will recognize that ISF extraction devices according to the present invention can be employed in a variety of systcrns including, hut not Iirnited to, systems for 'the extraction of a bodily fluid sample; and monitoring of an analgrte t;~erein, as described above. For example, the ISF extraction devices can be employed in a sample mod=ale of such systems.
[OOI03j Deferring to FICi. 13, a method 1000 for continuous collection of an ISF sample from a user's skin layer according to an exemplary err~bodient of the present invention includes providing an ISF fluid extraction device, as set forth in step 1010. The ISF fluid extraction device that is provided includes a penetration member and at least one pressure ring (c.g." a single pressure ring or tln-ee concentric pressure rings). The penetration member and pressure rings) can be penetration members and pressure r~ngs, as described above with respect to ISF' extraction devices and systems according to the present invention.
[00104] Next, as set forth in step 1020, the pressure rings) is contacted with a user's skin layer in the vicinity of a target site (e.g., fnger tip derrraal tissue 'target site, a limb target site, an abdomen target site or other target site from which an ISF sample is to be extracted). The pressure ring can be contacted to the user's skin layer using any suitable techniques including, for example, those described above with r°espect to embodiments of systems and devices according to the present isavention.
[OOlOSj The target site of the user's skin layer is then penetrated by penetration member, as set forth in step 1030. Next, ISF is extracted frorm the user's skin layer by the penetration member while pressure is applied to the user's skin layer in an oscillating manner that mitigates an ISF lag of the extracted ISh, as set forth in step 10=l0. The various oscillating ananners, by which pressure is applied, in methods 2~

according to the present invention have been described above with respect to FIGs. 1-12.
(00106] The following examples serve to illustrate beneficial aspects of various embodiments of devices, systems and methods according to il~e present invention.
[00107] Example 1: Impact of an oscillating_pressure ri.n~ on blood perfusion in an area within the oscillating~~ssure ring [OOlOg] Laser Doppler image perfusion data were collected at semi-regular intervals from a 0.25 square centimeter area approximately centered in the inside of a pressure ring attached to a subject's forearm. 'The pressure ring had an outside diameter of 0.53 inches and a wall thickness of 0.03 inches. Baseline data were collected prior to deploying the preasure ring against the subje;it's skin layer. The pressure ring was deployed against. the skin layer for IO minutes with a spring force of 0.5 lbs, retracted from the skin layf;r I'or 3Q minutes, and then this cycle of deployment and retraction was repeated. The pressure ring was subsequently deployed against the skin layer for 5 hours, raised for I hour, and finally deployed against the skin for 1 Q
minutes. The average perfusions in the 0.25 cm sq_ measurement area are shown in the graph of FIG. 12.
[00109] As can be seen in the graph in FIG. I2, deployment of the pressure ring reduced blood perfusion in the area enclosed by the pressure r ng (i.e., blood. perfusion was reduced with the application ofpressure), in comparison t:o the baseline blood perfusion. :~Iowever, removing the pressure ring (i.e., releasing the pressure) not only reversed this effect, but actually increased perfusion beyond the baseline.
Example ~- Impact of an osciilatina pressure rip og_n ISF~ylucose lag (00110] A study was performed to determine the impact of blood Claw on ISF
glucose values during use of an oscillating pressure ring according to exemplary embodiments of the present invention. 'twenty diabetic subjects underwent a 2$

procedure, in which baseline blood perfusion measurements were made on volar and dorsal portions of the subject's forearms. The subjects then participated in a test, in which finger blood samples, control 1SF samples and treated ISF samples vrere collected at 15 minute intervals over a period of 3 to 6 hours. ~.ontrol 1SF
samples were obtained from the subject's forearms without any skin layer manipulation and treated ISF samples were obtainea! by manipulating the subject's skin layer with an oscillating pressure ring. During t:he 3 to 6 hour testing period, blood glucose was influenced by ingestion of a microwave meal and diabetes medications including insulin and oral hypoglycemics such that most subjects experienced a rise and fall in blood glucose.
~OOlllJ The treated 1SF samples were created by applying approximavtely 1S~D
pounds per square inch of pressure with a pressure ring with no sampling for seconds, followed by a 5 rrQinute v~~aiting period ts~ allow blood to perfusc into the sampling target site. BIood perfusion measurements were made with a Moor Laser Doppler Imager (Devon, IJK~ immediately prior to obtaining both control and treated 1SF samples. Laser Doppler irnaging was performed over a 2 square centimeter area centered on the ISF sampling target site.
X00112] iSF glucose measurements were made with a modified ~neTouch~
Ultra° glucose meter and test strip system. A sample of about 1 ~.L of 1SF was extracted from the dermis of the suibject's skin layer by a needle and deposited automatically into a measurement :zone ofthe test strip. urn unrr~odifaed t~ncTouch~
Ultra glucose meter and strip system was used to determine whole blood glucose values from the f nger.
[00113] Lag times in minutes and perfusion measurements are given in Table 1 for each subject.

[00114] TABLE 1 controltreatment area area treatmentcontroltreatment mean rraean to ISF I;s~ overall control blood blood food overalloveralllag Subjectperfusionerfusionerfusionlag lag itigation )I9 units u~Eits atio (min.)(~nin.}(min.) 8 97.1 2I2.9 2.19 30 10 20 9 65.3 17_0.3 2.6I 21 5 X 16 _ 84.0 187.6 2.23 26 4 22 11 50.2 117.3 2.34 22 -S 27 12 68.4 223.5 3.27 12 -2 14 13 95.4 295.2 3.09 30 I.'~ 15 ~

14 62.0 150.3 2.42 47 12 35 51.7 92._8 1.80 50 10 40 _-16 80.0 80.9 1.01 41 ~ ~

17 64.6 107.8 I.67 46 12 34 , 18 101.2 244.4 2.4I 50 11. 39 X

19 86.2 142.4 I .65 27 1 ~i 11 0 II4.8 256.8 2.24 42 16 26 21 1 i8.6198.3 1.67 13 5 8 22 73.2 156.:? 2.I3 25 8 I7 ~' 23 114.7 278.2 2.43 30 8 22 24 94.4 253.6 .69 15 8 7 ~ ~~

16 482.13 2.99 8 - 2 10 I
.2 6 58.7 15I.7 .59 42 9 33 27 114.6 363.3 3.17 29 8 i 21 ~

28 56.3 117.0 2.08 1 10 21 mean: 86.3 203.9 2.32 0.3 8.7 21.7 X 3 !

SD. 28.1 97.2 0.6 2.8 .6 j 9.9 [00115 The data in Table 1 show that ISF glucose lag was mitigated an average of 21.7 minutes, i.e., from a mean of 30.3 minutes ( 12.8 SD) to a mean of 8.7 minutes (6.6 SIB) by use of the oscillating pressure ring. This lag mitigation was accomplished by the application and release of pressure to the ~~abject's skin layer in a manner that caused an elevation of local blood perfusion in the ISF sampling areas by an average of 2.3 times (0.6 SI3) relative to control sampling areas.

00116) While preferred en~bodirnents of the present invention have been shown and described herein, it gill be obvious to those skilled in the art that such embodiments are provided by way of exaanple only. Numerous ~~ariations, changes, and substitutions will now occur to those skilled in the art without departing from the invention.
[t7(911?] It should be understood that various alternatives to the embodiments of the invention described herein ~nay'oe employed in practicing the invention.
It is intended that the following claims define the scope of the in ention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (23)

1. A system for extracting a bodily fluid sample and monitoring an analyte therein, the system comprising:
a disposable cartridge including:
a sampling module adapted to extract a bodily fluid sample from a body; and an analysis module adapted to measure an analyte in the bodily fluid sample; and a local controller module in electronic communication with the disposable cartridge, the local controller adapted to receive measurement data from the analysis module and store the data.

2. The system of claim 1, wherein sampling module is adapted to extract an interstitial fluid (ISF) sample and to measure glucose in the ISF sample.

3. The system of claim 2, wherein the sampling module includes:
a penetration member configured for penetrating a target site of a user's skin layer and, subsequently, residing in the user's skin layer and extracting an ISF sample therefrom; and at least one pressure ring adapted for applying pressure to the user's skin layer in the vicinity of the target site while the penetration member is residing in the user's skin layer, wherein the sampling module is configured such that the pressure ring is capable of applying the pressure in an oscillating manner whereby an ISF
glucose lag of the ISF sample extracted by the penetration member is mitigated.

4. The system of claim 1, wherein the disposable cartridge and local controller are configured to be worn on the body.

5. The system of claim 1 further comprising:
a remote controller module adapted to electronically communicate with the local controller module.

6. The system of claim 5, wherein the remote controller module is configured to receive a glucose test strip and to measure glucose concentration of a blood sample applied to the glucose test strip.

7. The system of claim 5, wherein the remote controller module is adapted to employ a predictive algorithm to predict a blood glucose concentration based on an ISF glucose concentration determined by the local controller module.

8. The system of claim 73 wherein the remote controller module employs an algorithm of the following form:
FBGC = f(ISF i k, rate, ma n rate m p, interaction terms]
where:
PBGC is a predicted blood glucose concentration;
i is an integer of value between 0 and 3;
j, n, and m are integers of value between 1 and 3;
k and p are integers of value 1 or 2;
ISF i is a measured ISF glucose value;
rate j is the rate of change between measured ISF glucose values; and ma n rate m is the moving average rate between averages of groupings of ISF
glucose values.

9. The system of claim 1, wherein the sampling module includes:
a penetration member;
a launching mechanism; and a least one pressure ring.

10. The system of claim 1, wherein the sampling module is adapted to provide a continuous flow of extracted bodily fluid sample to the analysis module.

11. The system of claim 1, wherein the disposable cartridge and local controller module are configured for attachment to the user's skin

12. An interstitial fluid (ISF) extraction device comprising:
a penetration member configured for penetrating a target site of a user's skin layer and, subsequently, residing in the user's skin layer and extracting an ISF sample therefrom; and at least one pressure ring adapted for applying pressure to the user's skin layer in the vicinity of the target site while the penetration member is residing in the user's skin layer, wherein the ISF extraction device is configured such that the pressure ring is capable of applying the pressure in an oscillating manner whereby an ISF
glucose lag of the ISF sample extracted by the penetration member is mitigated.

13. The ISF extraction device of claim 12, wherein the ISF extraction device is configured such drat the pressure ring is capable of applying the pressure in an oscillating manner wherein the pressure is applied for a time period in the range of three seconds to three hours, the pressure is subsequently removed for a time period in the range of three seconds to three hours and then the pressure is re-applied for a period in the range three seconds to three hours.

14. The ISF extraction device of claim 12 further comprising:
at least one first biasing member configured for moving the pressure ring between a deployed state and a. retracted state; and a second biasing member configured for launching the penetration member.

15. The ISF extraction device of claim 12, wherein the penetration member is configured to reside in the user's skin layer for a period of at least 1 hour.

16. The ISF extraction device of claim 12, wherein the at least one pressure ring is a plurality of pressure rings.

17. The ISF extraction device of claim 16, wherein the pressure rings are arranged concentrically.

18. The ISF extraction device of claim 12, wherein the pressure ring and the first biasing element are configured to apply a pressure in the range of 0.1 to 150 pounds per square inch to a user's skin layer.

19. A method for extracting interstitial fluid (ISF), the method comprising:
providing an ISF fluid extraction device that includes a penetration member and at least one pressure ring;
contacting the pressure ring with a user's skin layer;
penetrating the user's skin layer with the penetration member; and extracting an ISF sample from the user's skin layer with the penetration member while applying pressure to the user's skin layer in an oscillating manner using the pressure ring such that an ISF glucose lag of the ISF sample extracted by the penetration member is mitigated.

20. The method of claim 19, wherein the providing step includes providing an ISF fluid extraction device that includes a plurality of pressure rings.

21. The method of claim 20, wherein the providing step includes providing an ISF fluid extraction device with three concentrically arranged pressure rings.

22. The method of claim 19, wherein the extracting step includes applying pressure in an oscillating manner wherein the pressure is applied for a time period in the range of three seconds to tree hours, the pressure is subsequently removed for a time period in the range of three seconds to three hours and then the pressure is re-applied for a period in the range three seconds to three hours.

23. The method of claim 22, wherein the extracting step includes applying pressure in an asymmetric oscillating manner.