U.S. patent application number 11/858642 was filed with the patent office on 2008-01-10 for devices and methods for accessing and analyzing physiological fluid.
This patent application is currently assigned to LifeScan, Inc.. Invention is credited to Borzu SOHRAB.
Application Number | 20080009768 11/858642 |
Document ID | / |
Family ID | 29249849 |
Filed Date | 2008-01-10 |
United States Patent
Application |
20080009768 |
Kind Code |
A1 |
SOHRAB; Borzu |
January 10, 2008 |
Devices and Methods for Accessing and Analyzing Physiological
Fluid
Abstract
Systems, devices and methods for determining the concentration
of physiological fluid analytes are provided. The subject systems
have a plurality of biosensor devices present on a disposable
cartridge. Each biosensor device includes a biosensor and a skin
penetration means. In practicing the subject methods, a movement
means of the device is used to move each biosensor device in a
first direction that provides for penetration of the skin-piercing
means into a skin layer followed by movement of the biosensor in a
second direction that provides for removal of the skin-piercing
means from the skin layer, where this movement profile provides for
physiological fluid access and analyte concentration determination
by the analyte sensor means. The subject systems, devices and
methods for using the same find use in determining the
concentration of a variety of different physiological fluid
analytes, and are particularly suited for use in detection of
physiological fluid glucose concentration.
Inventors: |
SOHRAB; Borzu; (Los Altos,
CA) |
Correspondence
Address: |
PHILIP S. JOHNSON;JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Assignee: |
LifeScan, Inc.
Milpitas
CA
|
Family ID: |
29249849 |
Appl. No.: |
11/858642 |
Filed: |
September 20, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10143253 |
May 9, 2002 |
|
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11858642 |
Sep 20, 2007 |
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Current U.S.
Class: |
600/583 |
Current CPC
Class: |
A61B 5/150022 20130101;
A61B 5/157 20130101; A61B 5/15153 20130101; A61B 5/150442 20130101;
A61B 5/15126 20130101; A61B 5/150419 20130101; A61B 5/150213
20130101; A61B 5/150809 20130101; A61B 5/150824 20130101; A61B
5/15146 20130101; A61B 5/150305 20130101; A61B 5/150969 20130101;
A61B 5/150862 20130101; A61B 5/15159 20130101; A61B 5/150358
20130101 |
Class at
Publication: |
600/583 |
International
Class: |
A61B 5/157 20060101
A61B005/157 |
Claims
1. A system comprising: a housing including a plurality of devices,
each device comprising: (i) a skin-piercing member configured to
access physiological fluid beneath a skin surface; (ii) a biosensor
configured to measure a characteristic of the accessed
physiological fluid, the skin-piercing member being integrated with
the biosensor via a physiological fluid transfer pathway; and the
housing having a ramped surface and an advancing member configured
to move each device so that the skin-piercing member cooperates
with the ramped surface to deflect the skin-piercing member and
penetrate the skin surface at an oblique angle relative to the skin
surface.
2. The system according to claim 1, wherein each device comprises a
planar configuration wherein the skin-piercing member extends
therefrom.
3. The system according to claim 2, wherein the skin-piercing
member extends substantially within a same plane as the planar
configuration.
4. The system according to claim 3, wherein each device defines a
biosensor having a test strip configuration and the skin-piercing
member extends from the biosensor.
5. The system according to claim 2, wherein the skin-piercing
member extends in a direction substantially transverse to the
device.
6. The system according to claim 5, wherein each device defines a
frame having a biosensor portion and a skin-piercing portion spaced
apart from each other.
7. The system according to claim 1 wherein each device comprises an
angled configuration having a distal end defining the skin-piercing
member and a proximal end defining the biosensor.
8-9. (canceled)
10. A system comprising: a housing, the housing having a
skin-facing portion; an aperture within the skin-facing portion; a
cartridge receivable within the housing, the cartridge comprising a
plurality of devices, each device comprising: (i) a skin-piercing
member configured to access physiological fluid beneath a skin
surface; (ii) a biosensor configured to measure a characteristic of
the accessed physiological fluid, the skin-piercing member being
integrated with the biosensor via a physiological fluid transfer
pathway; the housing further comprising a ramped surface; an
advancing member configured to move each device so that the
skin-piercing member cooperates with the ramped surface to deflect
the skin-piercing member towards the aperture and pierce the skin
surface; and a meter disposed within the housing, the meter
configured to measure a characteristic of the physiological fluid
by applying a signal to the biosensor and receiving a resulting
signal from the biosensor.
11-15. (canceled)
16. The system according to claim 10, wherein the advancing member
is configured to move each device relative to the aperture in a
forward and a reverse direction.
17. The system according to claim 10, wherein the advancing member
is configured to rotate the cartridge.
18. The system according to claim 10, wherein a motor is configured
to move the advancing member.
19-25. (canceled)
26. The system according to claim 1, wherein the plurality of
devices is provided in a cartridge, the cartridge comprising a
frame and a plurality of torsion bars attached to the frame,
wherein each device is operatively attached to a torsion bar.
27. The system according to claim 26, wherein each torsion bar
allows the device to be movable relative to the frame.
28. The system according to claim 27, wherein each torsion bar
allows the device to rotate at least partially about an axis
defined by the torsion bar.
29. The system according to claim 28, wherein the axis of rotation
is perpendicular to a path along which the cartridge is caused to
travel.
30. The system according to claim 26, wherein the cartridge
comprises a disk configuration and wherein a serial arrangement of
the plurality of devices is about a circumference of the
cartridge.
31-36. (canceled)
37. A method for accessing a physiological fluid sample of a host
and measuring the concentration of an analyte within the
physiological fluid, comprising: (a) providing a cartridge in
planar apposition to a skin surface of the host, the cartridge
comprising a plurality of devices; (b) moving the cartridge in a
first direction, thereby causing an advancing member to cause a
skin-piercing member to penetrate a skin surface at an oblique
angle relative to the skin surface (c) transferring the
physiological fluid from the skin-piercing member to the biosensor
via a physiological fluid pathway; and (d) moving the cartridge in
a second direction to cause the advancing member to retract the
skin-piercing member from the skin surface.
38. The method according to claim 37, further comprising repeating
steps (b), (c) and (d) for each device of the plurality of
devices.
39. The method according to claim 38, wherein the step of repeating
occurs according to a predefined time schedule.
40. A method for accessing a physiological fluid of a host,
comprising (a) providing a system including a housing having a
skin-facing portion; an aperture within the skin-facing portion; a
cartridge receivable within the housing, the cartridge comprising a
plurality of devices, each device comprising: (i) a skin-piercing
member configured to access physiological fluid beneath a skin
surface; (ii) a biosensor configured to measure a characteristic of
the accessed physiological fluid, the skin-piercing member being
integrated with the biosensor via a physiological fluid transfer
pathway; the housing further comprising a ramped surface; an
advancing member configured to move each device so that the
skin-piercing member cooperates with the ramped surface to deflect
the skin-piercing member towards the aperture and pierce the skin
surface; and a meter disposed within the housing, the meter
configured to measure a characteristic of the physiological fluid
by applying a signal to the biosensor and receiving a resulting
signal from the biosensor, wherein the skin-facing portion of the
housing is in contact with a section of a skin surface; (b) moving
the cartridge in a first direction to cause an advancing member to
permit the skin-piercing member to move towards the aperture in the
housing and penetrate the skin surface; (c) transferring the
physiological fluid from the skin-piercing member to the biosensor
via the physiological fluid pathway; and (d) moving the cartridge
in a second direction to cause the advancing member to retract the
skin-piercing member from the skin surface.
41. The method according to claim 40, further comprising repeating
steps (b), (c), and (d) for each device of the plurality of
devices.
42. The method according to claim 40, further comprising the step
of measuring the analyte concentration.
43. The method according to claim 42, further comprising the step
of displaying the analyte concentration following the measurement
step.
44. The method according to claim 41, wherein the step of repeating
occurs according to a predefined time schedule.
45-50. (canceled)
51. A system comprising: a housing, the housing including a
skin-facing portion and an aperture within the skin-facing portion;
a cartridge receivable within the housing, the housing including a
plurality of devices, each device comprising: (i) a skin-piercing
member configured to access physiological fluid beneath a skin
surface; (ii) a biosensor configured to measure a characteristic of
the accessed physiological fluid, the skin-piercing member being
integrated with the biosensor via a physiological fluid transfer
pathway; an advancing member configured to move the cartridge
within the housing so that each device is positioned relative to an
aperture, the advancing member having a clip configured to hold the
biosensor; and a meter disposed within the housing, the meter
configured to measure a characteristic of the physiological fluid
by applying a signal to the biosensor and receiving a resulting
signal from the biosensor.
Description
FIELD OF THE INVENTION
[0001] The field of this invention is analyte concentration
detection, particularly physiological fluid access and the
determination of one or more analyte concentrations thereof.
BACKGROUND OF THE INVENTION
[0002] Analyte detection in physiological fluids, e.g., blood or
blood derived products, physiological fluid, etc., is of ever
increasing importance to today's society. Analyte detection assays
find use in a variety of applications, including clinical
laboratory testing, home testing, etc., where the results of such
testing play a prominent role in diagnosis and management in a
variety of disease conditions. Analytes of interest include glucose
for diabetes management, cholesterol, and the like. In response to
this growing importance of analyte detection, a variety of analyte
detection protocols and devices for both clinical and home use have
been developed.
[0003] In determining the concentration of an analyte in a
physiological sample, a physiological sample must first be
obtained. Obtaining the sample often involves cumbersome and
complicated devices which may not be easy to use or may be costly
to manufacture. Furthermore, the procedure for obtaining the sample
may be painful. For example, pain is often associated with the size
of the needle used to obtain the physiological sample and the depth
to which the needle is inserted. Depending on the analyte and the
type of test employed, a relatively large, single needle or the
like is often used to extract the requisite amount of sample.
[0004] The analyte concentration determination process may also
involve a multitude of steps. First, a sample is accessed by use of
a skin-piercing mechanism, e.g., a needle or lancet, which
accessing may also involve the use of a sample collection
mechanism, e.g., a capillary tube. Next, the sample must then be
transferred to a testing device, e.g., a test strip or the like,
and then oftentimes the test strip is then transferred to a
measuring device such as a meter. Thus, the steps of accessing the
sample, collecting the sample, transferring the sample to a
biosensor, and measuring the analyte concentration in the sample
are often performed as separate, consecutive steps with various
device and instrumentation.
[0005] Because of these disadvantages, it is not uncommon for
patients who require frequent monitoring of an analyte to simply
become non-compliant in monitoring themselves. With diabetics, for
example, the failure to measure their glucose level on a prescribed
basis results in a lack of information necessary to properly
control the level of glucose. Uncontrolled glucose levels can be
very dangerous and even life threatening.
[0006] Advances have been made in analyte detection technology to
overcome the disadvantages of the above described testing
protocols. A primary advancement is the integration of the means
for accessing physiological fluid and the means for testing the
fluid for the presence and/or concentration of the analyte of
interest, e.g., glucose. More specifically, such integrated devices
include a biosensor having a skin-piercing element, such as a
microneedle, integrated therewith. Such exemplary devices are
disclosed in, for example, the following U.S. patent applications:
Ser. No. 09/923,093; the application having Attorney Docket No.
LIFE-035, entitled "Physiological Sample Collection Devices and
Methods of Using the Same" and filed on the same day herewith; the
application having Attorney Docket No. LIFE-058, entitled "Analyte
Test Element with Molded Lancing Blade" and filed on the same day
herewith; and the application having Attorney Docket No. LIFE-073,
entitled "Methods of Fabricating Physiological Sample Collection
Devices" and filed on the same day herewith.
[0007] Despite such advancements, there is a continued interest in
the development of new devices and methods for use in the
determination of analyte concentrations in a physiological sample.
Of particular interest would be the development of analyte
concentration determination systems having integrated fluid
accessing and testing functions, and methods of use thereof, that
are automated in order to minimize manipulation by the user,
convenient, easy and discrete to use, involve minimal pain, and
enhance portability.
SUMMARY OF THE INVENTION
[0008] Systems, devices and methods for accessing physiological
fluid and determining the concentration of one or more analytes
thereof. The subject systems provide a cartridge device containing
a plurality of single-use biosensor/skin-piercing/fluid access
devices. The cartridge devices of the present invention have a flat
or planar construct, and preferably have a disk shape but may have
an elongated shape. The biosensor/skin-piercing/fluid access
devices are provided within the cartridge in a serial
configuration, preferably equally spaced from each other, parallel
to a path along which the cartridge is caused to move or rotate. In
disked shaped cartridges, such serial arrangement is about a
circumference of the cartridge.
[0009] The subject systems further include a housing structure
within which a cartridge is operatively loaded. The housing
structure preferably has a skin-facing portion and/or surface which
appositions a loaded cartridge loaded within to a section of the
user's skin. The housing is preferably configured so as to be
maintained against the skin for extended periods. To this end, the
housing may have a "watchband" configuration to be worn on a limbic
region, e.g., a wrist or forearm, of the user, or may have a
configuration, such as a substantially planar configuration, for
adhesive contact with a suitable location, e.g., torso, thigh, hip,
etc., on the user's body.
[0010] Each biosensor/skin-piercing/fluid access device has a
biosensor integrated with a skin-piercing or lancing element for
piercing, cutting or lancing the skin and, in some embodiments,
also includes a fluid collection channel or transfer pathway for
transferring the sampled physiological fluid within the skin to the
biosensor portion of the device. The biosensors may have an
electrochemical, photometric or colorimetric configuration by which
to perform a measurement on the sampled fluid. In some embodiments,
the biosensor devices have a generally planar configuration wherein
at least one skin-piercing member extends from the biosensor
device. In certain of these embodiments, the skin-piercing member
extends substantially within the same plane as the planar biosensor
device, while in other embodiments, the skin-piercing member
extends in a direction substantially transverse to the planar
configuration of the biosensor device. More specifically, in some
embodiments, the biosensor devices are configured as test strips
wherein the skin-piercing element extends from a member or
component, e.g., a substrate, an electrode or spacer layer, of the
test strip. Certain other embodiments provide a frame member having
a planar configuration having a biosensor pad or strip and a
micro-lancing element mounted on and integrated to the same planar
surface, but are spaced apart from each other to facilitate the
function of that particular device. In still other embodiments, an
angled structure is provided which extends distally into at least
one microneedle formation and which supports a biosensor chamber at
a proximal end thereof.
[0011] The subject systems further include a meter housed within
the housing structure for analyzing the physiological fluid
obtained by the biosensor/skin-piercing/fluid access devices.
Connectors or contacts are provided to operatively couple the
biosensor devices with the meter whereby the meter provides the
requisite signals to the biosensor devices to perform the assay
measurement and includes means for determining the value of such
measurement.
[0012] The subject system further provides means for operatively
moving, e.g., advancing and reversing, a subject cartridge relative
to an aperture in the housing structure for exposing and concealing
an individual biosensor/skin-piercing/fluid access device through
the aperture to an access site on the user's skin. Alternately, at
least a portion of the apertured housing structure is moveable to
expose and unexposed an individual biosensor/skin-piercing/fluid
access device. Such movement of the cartridge places the exposed
biosensor devices in operative connection, via connectors and
contacts, to the meter.
[0013] While the biosensor devices translate along with the
cartridge device, in some embodiments, each biosensor device is
operatively attached to the cartridge device so as to be movable
relative to the cartridge device so as to optimize the angle by
which the skin is to be pierced by the skin-piercing means, thereby
reducing pain to the patient and trauma to the skin. Such movement
involves deflection and/or rotation of a biosensor device about an
axis which extends radially or perpendicular to the path through
which the biosensors are caused to travel upon translation of the
cartridge device. The movement of the biosensor devices relative to
the cartridge is primarily accomplished passively such as by
components fixed within the housing structure relative to the
cartridge for advancing or deflecting each individual
biosensor/skin-piercing/fluid access device through the housing
aperture towards an access site on the user, penetrating the access
site with the skin-piercing element and then withdrawing or
retracting the device from the access site. Such components include
but are not limited to ramp structures and clip mechanisms.
[0014] The subject systems may further include a controller, such
as in the form of a microprocessor, for controlling the function of
the meter and the movement of the cartridge and the biosensor
devices, and for storing data related thereto. The controller is
programmable whereby the assay protocol and the timing thereof may
be customized according to software algorithms. Such algorithms
provided for the "continuous" monitoring of concentration of an
analyte in a user, i.e., for automatically measuring the
concentration of an analyte in a user according to a predetermined
scheduled, e.g., at two or more points over a given time period.
The systems may also provide for the user to implement an assay "on
demand," thereby overriding the continuous monitoring protocol.
Such analyte concentration measurements are stored by the
microprocessor or other memory storage means for immediate or later
retrieval by the user or a physician. The subject systems may
further include a display means for displaying the results of the
assay and other relevant information. In certain embodiments, such
systems include means for communicating with external devices for
the transfer and receipt of information and data related to the
assay results, the assay protocol, the user, the disposable
cartridge, etc.
[0015] In practicing the subject methods, assay protocols are
implement which involve accessing physiological fluid by piercing
the user's skin with the skin-piercing element, collecting the
accessed physiological fluid to within the biosensor and measuring
the one or more target analytes within the physiological fluid.
Each assay protocol involves the advancement or movement of the
cartridge or an aperture associated therewith in a first direction
that causes the skin-piercing element of an integrated biosensor
device to penetrate the skin, followed by movement of the cartridge
or aperture in a second direction that provides for removal of the
skin-piercing element from the skin, where this movement profile
provides for physiological fluid access and analyte concentration
determination by the biosensor. Advancement of the cartridge or
aperture may be performed manually by the user or driven by a motor
controlled by the controller. Such advancement and skin-penetration
may be done automatically according to a preprogrammed scheduled or
at the will of the user.
[0016] The subject systems, devices and methods for using the same
find use provide a repeatable fluid accessing and sampling
interface between a biosensor and a target skin site for
determining a chemical characteristic of the sampled fluid,
typically, the concentration of a variety of different
physiological fluid analytes, and most typically the concentration
of glucose. The subject system and devices can be used in the
continual measurement of an analyte of interest without the
problems experienced with implantable analyte sensors. For example,
because single-use substantially painless analyte measurement means
are employed, user irritation and pain are avoided. Furthermore,
the individual measurement means employed need not be calibrated
prior to use. In addition, with respect to the glucose the subject
devices and methods can not only be employed to rapidly and
accurately detect the occurrence of a hypo or hyperglycemic event
without host participation or intervention, but they can also be
employed to readily predict the occurrence of hypo and
hyperglycemic conditions, and therefore provide for improved
management of blood glucose metabolism associated disease
conditions. As such, the subject invention represents a significant
contribution to the art.
[0017] These and other objects, advantages, and features of the
invention will become apparent to those persons skilled in the art
upon reading the details of the methods and systems of the present
invention which are more fully described below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1A is an exploded view of an embodiment of an
electrochemical biosensor/skin-piercing/fluid access device
suitable for use with the cartridge devices and systems of the
present invention. FIG. 1B is a perspective view of the assembled
device of FIG. 1A.
[0019] FIG. 2A is an exploded view of an embodiment of a
calorimetric or photometric biosensor/skin-piercing/fluid access
device suitable for use with the cartridge devices and systems of
the present invention. FIG. 2B is a perspective view of the
assembled device of FIG. 2A
[0020] FIG. 3 illustrates yet another embodiment of an
electrochemical biosensor/skin-piercing/fluid access device
suitable for use with the cartridge devices and systems of the
present invention.
[0021] FIG. 4 illustrates another embodiment of an electrochemical
biosensor/skin-piercing/fluid access device suitable for use with
the cartridge devices and systems of the present invention.
[0022] FIG. 5A illustrates another embodiment of a
biosensor/skin-piercing/fluid access device suitable for use with
the cartridge devices and systems of the present invention. FIG. 5B
is a magnified view of the skin-piercing element of the device of
FIG. 5A.
[0023] FIG. 6A is a top view of an embodiment of the system of the
present invention having a user-friendly, portable configuration.
FIG. 6B is a side view of the system of FIG. 6A taken along lines
B-B. FIG. 6C is a bottom view of the systems of FIG. 6B taken along
lines C-C. FIG. 6D illustrates the system of FIGS. 6A, 6B and 6C in
an open condition, revealing a cartridge device of the present
invention operatively positioned within the housing go the subject
system.
[0024] FIG. 7A is a schematic representation of one embodiment of a
cartridge device of the present invention. FIG. 7B is a view of an
enlarged cut-away portion the cartridge device of FIG. 7A
operatively engaged with a bottom portion of a system housing
having an embodiment of a biosensor movement means of the present
invention.
[0025] FIGS. 8A to 8F provide a schematic representation of one
embodiment of a biosensor movement means of a system of the present
invention and the step-by-step movement of a
biosensor/skin-piercing/fluid access device of FIGS. 1, 2 or 3 on a
cartridge of the present invention.
[0026] FIGS. 9A to 9G provide a schematic representation of another
embodiment of a biosensor movement means of a system of the present
invention and the step-by-step movement of a
biosensor/skin-piercing/fluid access device of FIG. 4 on a
cartridge of the present invention,
[0027] FIGS. 10A to 10C provide a schematic representation of the
step-by-step movement of a cartridge of the present invention
employed with the biosensor/skin-piercing/fluid access device of
FIG. 4.
[0028] FIG. 11A illustrates "wristband" embodiment of the subject
system. FIG. 11B illustrates a "waistband" embodiment of the
subject system which is used with and in communication with a
remote control device.
DETAILED DESCRIPTION OF THE INVENTION
[0029] Before the present invention is described, it is to be
understood that this invention is not limited to the particular
embodiments described, as such may, of course, vary. It is also to
be understood that the terminology used herein is for the purpose
of describing particular embodiments only, and is not intended to
be limiting, since the scope of the present invention will be
limited only by the appended claims.
[0030] Where a range of values is provided, it is understood that
each intervening value, to the tenth of the unit of the lower limit
unless the context clearly dictates otherwise, between the upper
and lower limit of that range and any other stated or intervening
value in that stated range is encompassed within the invention. The
upper and lower limits of these smaller ranges may independently be
included in the smaller ranges is also encompassed within the
invention, subject to any specifically excluded limit in the stated
range. Where the stated range includes one or both of the limits,
ranges excluding either or both of those included limits are also
included in the invention.
[0031] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar or equivalent to those described
herein can also be used in the practice or testing of the present
invention, the preferred methods and materials are now
described.
[0032] It must be noted that as used herein and in the appended
claims, the singular forms "a", "an", and "the" include plural
referents unless the context clearly dictates otherwise. Thus, for
example, reference to "a test strip" includes a plurality of such
test strips and reference to "the device" includes reference to one
or more devices and equivalents thereof known to those skilled in
the art, and so forth.
[0033] The publications discussed herein are provided solely for
their disclosure prior to the filing date of the present
application. Nothing herein is to be construed as an admission that
the present invention is not entitled to antedate such publication
by virtue of prior invention. Further, the dates of publication
provided may be different from the actual publication dates which
may need to be independently confirmed.
[0034] The present invention will now be described in detail. In
further describing the present invention, exemplary integrated
biosensor/skin-piercing/fluid access devices suitable for use with
the present invention are described first. Next, the subject
systems and cartridge devices are described followed by a
description of the various methods of using the subject systems and
devices as well as methods for controlling the testing of
physiological sample characteristics will then be described.
Finally, a brief description is provided of the subject kits, which
kits include the subject cartridges and/or systems for use in
practicing the subject methods.
[0035] In the following description, the present invention will be
described in the context of analyte concentration measurement
applications; however, such is not intended to be limiting and
those skilled in the art will appreciate that the subject devices,
systems and methods are useful in the measurement of other physical
and chemical characteristics of biological substances, e.g., blood
coagulation time, blood cholesterol level, etc.
Exemplary Biosensor/Skin-Piercing/Fluid Access Devices
[0036] Various different embodiments of
biosensor/skin-piercing/fluid access devices (also referred to
herein as biosensor devices) may be employed with the present
invention. Biosensor/skin-piercing/fluid access devices suitable
for use with the present invention typically have a biosensor
component in the form of a test strip or pad, such as an
electrochemical, colorimetric or photometric test strip, and have a
skin-piercing component in the form of a microneedle or a
micro-lancet. Referring now to FIGS. 1A, 1B, 2A, 2B, 3, 4, 5A and
5B, there are shown such exemplary devices.
[0037] FIGS. 1A and 1B illustrate such an exemplary biosensor
device 2 which is disclosed in the copending U.S. patent
application referenced above having Attorney Docket No. 035, herein
incorporated by reference. Biosensor device 2 includes an
electrochemical test strip configuration and a microneedle 6
integrated therewith. The biosensor is defined by an
electrochemical cell generally having two spaced-apart and opposing
electrodes 3 and 5, respectively referred to herein as bottom
electrode 3 and top electrode 5. At least the surfaces of
electrodes 3 and 5 facing each other are comprised of a conductive
layer 8 and 16, respectively, such as a metal, deposited on an
inert substrate 4 and 18, respectively. The spacing between the two
electrodes is a result of the presence of a spacer layer 12
positioned or sandwiched between electrodes 3 and 5. Spacer layer
12 preferably has double-sided adhesive to hold electrodes 3 and 5
together. Spacer layer 12 is configured or cut so as to provide a
reaction zone or area 9. A redox reagent system or composition is
present within reaction zone 9, and specifically selected to
interact with targeted components in the fluid sample during an
assay of the sample. The redox reagent system is deposited on the
conductive layer of top electrode 5 wherein, when in a completely
assembled form (shown in FIG. 1B), the redox reagent system resides
within reaction zone 9. With such a configuration, bottom electrode
3 serves as a counter/reference electrode and top electrode 5
serves as the working electrode of the electrochemical cell.
However, in other embodiments, depending on the voltage sequence
applied to the cell, the role of the electrodes can be reversed
such that bottom electrode 3 serves as a working electrode and top
electrode 5 serves as a counter/reference electrode.
[0038] Microneedle 6 is integrally formed with and extends from and
in the same plane as bottom electrode 3 and terminates distally in
a sharp tapered tip 24 which facilitates penetration into the
user's skin. Microneedle 6 further provides a space-defining
configuration in the form of a concave recess 20 within its top
surface. Such recess creates a corresponding space within skin
tissue upon penetration of microneedle 6 into the skin. This space
acts as a sample fluid collection reservoir or pooling area wherein
fluid released upon penetration is pooled within the space prior to
transfer into the electrochemical cell. Optionally, microneedle 6
may further include an opening 22 in fluid communication with
recess 20 to facilitate the pooling rate of physiological fluid
within the defined pooling area.
[0039] Biosensor device 2 further includes a sample fluid transfer
or extraction pathway or channel 10 which extends from recess 20 to
within the biosensor. At least a portion of the proximal end 10a of
the pathway resides within the biosensor portion of device 2,
specifically within reaction zone 9, and a portion of distal end
10b of pathway 10 resides within microneedle 6. Pathway 10 is
dimensioned so as to exert a capillary force on fluid within the
pooling area defined by recess 20, and draws or wicks physiological
sample to within reaction zone 9. Extending laterally from proximal
portion 10a of pathway 10 to within a portion or the entirety of
the reaction zone 9 are sub-channels 15. Sub-channels 15 facilitate
the filling of reaction zone 9 with the sampled fluid.
[0040] FIGS. 2A and 2B illustrate another suitable embodiment of a
biosensor/skin-piercing/fluid access device 30 which is also
disclosed in copending U.S. patent Application having Attorney
Docket No. LIFE-035. Device 30 has a photometric/colorimetric
biosensor configuration and a microneedle 32 integrated therewith.
The colorimetric or photometric biosensor is generally made up of
at least the following components: a support element or substrate
34 made of either an inert material, such as plastic, or a metal
material, a matrix area 36 for receiving a sample, a reagent
composition (not shown as a structural component) within matrix
area 36 that typically includes one or more members of an analyte
oxidation signal producing system, an air venting port (not shown)
and a top layer 38 which covers at least matrix 36. In other
embodiments, top layer 38 may be a membrane containing a reagent
composition impregnated therein while the matrix area 36 may or may
not contain reagent composition. Further, test strip 30 has a
double-sided adhesive layer 40 situated between substrate 34 and
membrane 38 to hold them together. Double-sided adhesive layer 40
has a cut-out portion 42 which corresponds to the area covered by
matrix 36 and defines an area for deposition of the sampled
physiological fluid and for the various members of the signal
producing system.
[0041] Microneedle 32 is formed with and extends from and in
substantially the same plane as substrate 34 and has a
space-defining configuration in the form of an opening 44 which
extends transverse to a dimension, e.g., width or thickness, of
microneedle 32. As with recess 20 of microneedle 6 above, opening
44 forms an open space within the tissue upon penetration of
microneedle 32 into the skin. Such open space acts as a sample
fluid collection reservoir wherein fluid released upon penetration
is pooled within the space prior to transfer into the
photometric/colorimetric cell.
[0042] Biosensor device 30 hosts a sample fluid transfer or
extraction pathway 46 having a distal end 46b which extends within
a portion of microneedle 32 and terminates at a distal opening 48.
At least a portion of the proximal end 46a of pathway 46 resides
within the biosensor portion of device 30, specifically within
matrix area 36. Pathway 48 is dimensioned so as to exert a
capillary force on fluid within the pooling area defined by opening
44, and draws or wicks physiological sample to within matrix area
36. Extending laterally from proximal portion 46a of pathway 46 to
within a portion or the entirety of matrix area 36 are sub-channels
50, which facilitate the filling of matrix area 36 with the sampled
fluid.
[0043] FIG. 3 illustrates another exemplary biosensor device 60,
disclosed in copending U.S. patent application Ser. No. 09/923,093,
herein incorporated by reference, which is suitable for use with
the present invention. Device 60 has an electrochemical test strip
configuration similar to device 2 of FIGS. 1A and 1B, having a
first electrode 62 with an associated inert substrate 64, a second
electrode 66 with an associated inert substrate 68 and a spacer
layer 70 there between which, collectively, form a reaction zone 72
having an appropriate redox reagent system. Instead of a single
microneedle extending from an electrode or substrate thereof, as
described with respect to the devices of FIGS. 1 and 2, device 60
has a plurality of skin-piercing elements 74 extending from and in
substantially the same plane as spacer layer 70. Skin-piercing
elements 74 may be made of the same material as spacer layer 70 or
of a different material. Skin-piercing elements 74 each have a
fluid channel 76 which extends proximally into spacer layer 70 to
reaction zone 72. Each fluid channel 76 is open to the outside
environment along a substantial length of a first side 78 and a
second side 80 of the respective skin-piercing element and
terminates proximal to distal tip 82 of the skin-piercing element
74. Channels 76 are dimensioned to exert a capillary force for
collecting and transferring physiological sample accessed by the
skin-piercing element 74. While each skin-piercing element is
illustrated having a single fluid pathway 76, a plurality of such
pathways may be used in each skin-piercing element 74.
[0044] FIG. 4 illustrates another suitable embodiment of a
biosensor/skin-piercing/fluid access device 90 having an angled
structure. Device 90 includes two piercing/fluid sampling
microneedles 92, each including a flow pathway 96 extending from a
distal opening 94 to a reaction zone or matrix area 100 of a
proximal biosensor 98. The angled structures are typically
elongated structures characterized by the presence of a single bend
located proximal to the center of the elongated structure. The
number of skin piercing structures, and thus the number of flow
pathways, may vary, typically ranging from about 1 to 5, usually
from about 1 to 4 and more usually from about 1 to 3, where the
number of piercing elements typically ranges from 1 to 2 in many
embodiments. The angle of the single bend typically ranges from
about 135.degree. to 150.degree. and more usually from about
140.degree. to 145.degree.. The length from the bend to the very
tip of the elongated angular structures typically ranges from about
2.3 to 3.2 .mu.m and more usually from about 2.6 to 3.0.
[0045] The fluid flow pathways 96 have capillary dimensions that
result in capillary flow of accessed physiological fluid from the
distal openings 94 along the length of the flow pathway to the
biosensor 98. As the flow path is one that has capillary
dimensions, the flow path typically has a diameter at any point
along its length in the range from about 80 to 150 .mu.m. The flow
path may be tubular or have some other configuration, e.g., one
that provides for a cross-sectional shape that is a square,
rectangle, oval, star, etc., where the configuration of the flow
path is not critical so long as it provides for the desired
capillary flow.
[0046] Biosensor 98 typically is made up of a sensor chamber that
includes a transducing means which produces a signal in response to
the presence, and typically concentration of, analyte in
physiological fluid present in the chamber. The chamber located at
the proximal end of device 90 typically has a volume in the range
from about 100 to 300 .mu.L. The transducing means may be any
convenient transducing means that is capable of generating a signal
in response to the presence of analyte in fluid present in the
chamber. While in the broadest sense the transducing means may
produce a signal that is indicative of the presence of analyte, in
many preferred embodiments, the transducing means is one that
generates a signal that is proportional to the amount of analyte in
the physiological fluid.
[0047] One type of transducing means of interest that may be
present in the subject sensors is a photometric transducing means.
Photometric transducing means of interest typically include one or
more reagents of a signal producing system that produces a
detectable product in proportion to the amount of analyte present
in the chamber. The detectable product is then photometrically
detected to provide for a detection of the presence of analyte, and
typically a measurement of the concentration of analyte, that is
present in the fluid inside the chamber. Photometric transduction
means of interest that may be employed in such biosensor devices
include, but are not limited to, those described in U.S. Pat. Nos.
4,935,346; 5,049,487; 5,509,394; 5,179,005; 5,304,468; 5,426,032;
5,563,042; 5,843,692; and 5,968,760; the disclosures of which are
herein incorporated by reference.
[0048] Another type of transducing means of interest that may be
present in the subject sensors is an electrochemical transducing
means. Electrochemical transducing means of interest typically
include an electrochemical cell that includes two electrodes and
one or more reagents of signal producing system, where these
elements work in concert to produce an electrical current in
proportion to the amount of analyte present in the chamber. The
generated electrical current provides for a detection of the
presence of analyte, and typically a measurement of the
concentration of, analyte that is present in the fluid inside the
chamber. Electrochemical transduction means of interest that may be
employed in the biosensor devices include, but are not limited to,
those described in U.S. Pat. Nos. 5,834,224; 5,942,102; and
5,972,199; as well as U.S. patent application Ser. Nos. 09/333,793;
09/497,269 and 09/497,304; the disclosures of which are herein
incorporated by reference.
[0049] FIGS. 5A and 5B illustrate another exemplary embodiment of a
biosensor/skin-piercing/fluid access device 110 suitable for use
with the present invention, which device is disclosed in the
copending U.S. patent Application the referenced above having
Attorney Docket No. 058, herein incorporated by reference. Device
110 includes a planar frame 112, and a blade portion 114 and a
sensor portion 116 mounted on and carried by frame 112. Blade
portion 114 includes an intermediate wedge or raiser member 118
upon which is mounted a blade or lancing element 120 which extends
substantially transverse to planar frame 112. Member 118 serves to
elevate blade or lancing element 120 relative to a skin-facing
surface or face 122 of frame 112. Raiser member 118 has an angled
front surface or ramp portion 124 which allows for smooth
translational movement of device 110 relative to the skin of the
user. A landing area 126 is provided upon which blade 120 is
specifically mounted, the narrow construct of which acts to reduce
frictional forces with the user's skin while increasing the ability
to compress tissue riding over the structure. Blade 120 is provided
with a triangular shape having a larger base and substantially
vertical side portions, however, blade 120 may have any shape whose
geometry is robust enough to avoid break-off. Sensor portion 116 is
spaced apart from blade portion 114 to allow substantially flush
engagement by sensor portion 116 with the cut area of the user's
skin. Sensor portion 116 provides a sensor pad or area 128 for
receiving the access physiological fluid, i.e., interstitial fluid
or blood. Sensor pad 128 may have either an electrochemical or
photometric configuration as described above.
[0050] While specific configurations of
biosensor/skin-piercing/fluid access devices suitable for use with
the systems of the present invention have been illustrated and
described, it is understood that any type of biosensor, e.g.,
electrochemical, photometric, colorimetric, may be employed with
one or more suitable skin-piercing elements or microneedles.
Additionally, while specific shapes of skin-piercing elements and
microneedles have been illustrated and described, any suitable
shape of skin-piercing element may be employed with the biosensor
devices, as long as the shape enables the skin to be pierced with
minimal pain to the patient. For example, the skin-piercing element
may have a substantially flat or planar configuration, or may be
substantially cylindrical-like, wedge-like or triangular in shape
such as a substantially flattened triangle-like configuration,
blade-shaped, or have any other suitable shape. The cross-sectional
shape of the skin-piercing element, or at least the portion of
skin-piercing element that is penetrable into the skin, may be any
suitable shape, including, but not limited to, substantially
rectangular, oblong, square, oval, circular, diamond, triangular,
star, etc. Additionally, the skin-piercing element may be tapered
or may otherwise define a point or apex at its distal end. Such a
configuration may take the form of an oblique angle at the tip or a
pyramid or triangular shape or the like. The dimensions of the
skin-piercing element may vary depending on a variety of factors
such as the type of physiological sample to be obtained, the
desired penetration depth and the thickness of the skin layers of
the particular patient being tested. Generally, the skin-piercing
element is constructed to provide skin-piercing and fluid
extraction functions and, thus, is designed to be sufficiently
robust to withstand insertion into and withdrawal from the
skin.
[0051] In each embodiment, the biosensor/skin-piercing/fluid access
devices are configured so as to provide a repeatable interface with
the physiological fluid access site and with the target skin layer
when operatively employed with the cartridge devices and systems of
the present invention, which are now described in detail.
Systems of the Present Invention
[0052] Referring to FIGS. 6A, 6B, 6C and 6D, there is illustrated a
physiological sample collection and measurement system 200 of the
present invention having a compact, portable structural
configuration. This structure includes an ergonomic housing 202
having a top portion 204 and a bottom portion 206 hinged together
by hinge means 208 which allows top and bottom portions 204 and 206
to be opened apart and closed upon manual activation of depressible
key 226 or the like. FIG. 6D illustrates housing 202 in such an
open condition while FIGS. 6A, 6B and 6C illustrate housing 202 in
a closed condition. Together, top housing portion 204 and bottom
housing portion 206 define an interior compartment into which a
cartridge device 210 of the present invention is operatively loaded
and then removed after use. As will be described in greater detail
below with respect to FIGS. 7A and 7B, cartridge 210 contains or
provides one or more, and typically a plurality of, biosensor/fluid
access devices 220.
[0053] When properly loaded within the interior compartment of the
housing, the bottom surface of cartridge device 210 is positioned
adjacent the internal side of a bottom wall 212 of bottom housing
portion 206. Preferably, bottom wall 212 has an external surface
configuration which is smooth and contoured as necessary to be
flush against a selected area of the user's skin. Within bottom
wall 212 is an aperture 214, as shown in FIG. 6C, sized and
positioned such that a single biosensor/fluid access device 220 may
be aligned with and exposed through aperture 214 while the
remaining biosensor/fluid access devices 220 are concealed and
protected within bottom wall 210. Associated with aperture 214 are
contact means (not shown), e.g., electrical leads or an analogous
means, for communicating electrical signals between device 220 when
positioned at aperture 214 with a meter or measurement means (not
shown) housed within housing 202. Such electrical signals include
input signals from the meter to the device 220 for initiating the
chemical reaction between a sampled fluid and a reagent within
device 220 in order to determine a chemical characteristic, e.g.,
analyte (e.g., glucose) concentration, of fluid accessed and
sampled from the user's skin by means of a device 220.
[0054] Such measurement means has the necessary construct and
components for compatibility with the type of biosensor employed on
devices 220, e.g., an electrochemical, photometric or calorimetric
sensor. With an electrochemical based measurement system, the
electrochemical measurement that is made may vary depending on the
type of assay measurement and the meter employed, e.g., depending
on whether the assay is coulometric, amperometric or
potentiometric. Generally, the electrochemical measurement will
measure charge (coulometric), current (amperometric) or potential
(potentiometric), usually over a given period of time following
sample introduction into the reaction area. Methods for making the
above described electrochemical measurement are further described
in U.S. Pat. Nos. 4,224,125; 4,545,382; and 5,266,179; as well as
in International Patent Publications WO 97/18465 and WO 99/49307;
the disclosures of which are herein incorporated by reference. With
photometric/colorimetric assays, optical-type meters are used to
perform the assay. Such assays and methods and instruments for
performing the same, are further described in U.S. Pat. Nos.
4,734,360; 4,900,666; 4,935,346; 5,059,394; 5,304,468; 5,306,623;
5,418,142; 5,426,032; 5,515,170; 5,526,120; 5,563,042; 5,620,863;
5,753,429; 5,773,452; 5,780,304; 5,789,255; 5,843,691; 5,846,486;
5,968,836 and 5,972,294; the disclosures of which are herein
incorporated by reference.
[0055] System 200 further includes means for operatively moving
cartridge 210 within housing 202 so as to operatively move
cartridge 210 in order to sequentially position each
biosensor/fluid access device 220 at or relative to aperture 214.
Such cartridge movement involves advancement of cartridge 210 in
one direction, e.g., clockwise, and reversal of cartridge 210 in
the opposite direction, e.g., counter clockwise, relative to
aperture 214 to align a device 220 within aperture 214 and to
remove or conceal a device 220 from aperture 214. Such cartridge
movement means may be a motor-driven system, or the like, or may be
manually driven by the user by means of a ring or lever mechanism
external to housing 202. In a motor-driven system, cartridge 210
may be provided with a drive wheel 232 such that, when cartridge
device 210 is operatively loaded and positioned within housing 202,
drive wheel 232 is engaged with a drive shaft 234 for rotating
cartridge 210 in forward and reverse directions. Drive shaft 234 is
in turn rotated by a drive motor, also located within compartment
230.
[0056] System 200 also includes biosensor movement means (not
shown) associated with cartridge 210 at aperture 214 for applying a
force on each device 220 that is positioned at aperture 214. Such
biosensor movement means moves a device 220 downward from the
bottom surface of the cartridge on which all of the devices 220 are
positioned, and through aperture 214 so as to operatively contact
device 220 with the selected skin area. Such operative contact
involves piercing, cutting or lancing the skin surface with a
skin-piercing element provided on each device 220. Any convenient
means for applying such downward force on a device 220 may be
employed, where representative means include spring means or
analogous mechanical means, and the like, which are described in
greater detail below.
[0057] System 200 further includes a controller having a
microprocessor for controlling operation of the measurement means,
data processing means, automated cartridge movement means, and a
display 218 for displaying measurement data and other related data,
e.g., to inform the user when all of the devices 220 have been
used. The microprocessor may further be associated with a memory
storage means for the short-term or long-term storage of
measurement data. System 200 may further include a communication
module for the bidirectional communication with a remote control
device or and other devices, e.g., by wireless data communication
means, e.g., telemetry means, such as by infrared (IR) transmission
or radio frequency (RF) transmission, for the communication of
assay protocol programs and information and for the immediate or
later retrieval of measurement data and the like. System 200
further provides user control keys 224 on housing 202 to allow the
user to enter or select data or parameters from menus displayed on
the display, or to activate movement of the cartridge and an assay
protocol, which representative data signals are sent to the system
controller. System 200 may further control visual and audible
alarms which alert the user when it is time for an assay to be
performed, when a cartridge needs replacing, when an analyte
measurement is outside of safe range, etc. A power supply and a
battery are also provided to supply electrical power to the
cartridge motor, the microprocessor and all components controlled
by the microprocessor.
[0058] The system components just described may be housed in a
protective, sealed compartment 230 wherein the necessary data or
signal lines may run, for example, from compartment 230 in top
housing portion 204 through hinge 208 to bottom housing portion
206. Alternately, such data or signal lines may be provided within
top housing portion 204 such that they come into contact with
corresponding data or signal lines within bottom housing portion
306 when the housing is in a closed condition.
[0059] Referring now to FIG. 7A, there is shown a representation of
one embodiment of a cartridge device 300 of the present invention
suitable for use with at least the biosensor/skin-piercing/fluid
access devices of FIGS. 1, 2 and 3. Cartridge device 300 has a
cartridge body or frame 302 and a plurality of integrated
biosensor/skin-piercing/fluid access devices 304 (also referred to
herein as biosensor devices) positioned thereon, preferably in a
serial arrangement wherein devices 304 are evenly spaced apart from
each other. The cartridges of the present invention may host any
suitable number of integrated biosensor devices 304 wherein the
number of cartridges generally ranges from about 6 to 10.
[0060] In the annular or disk configuration of FIG. 7A, cartridge
body 302 is defined by concentric frame rings, outer frame ring
302a and inner frame ring 302b. Rings 302a and 302b are fixed
relative to each other by means of a plurality of torsion bars 306
which extend between rings 302a and 302b. Frame 304 is made of any
rigid material such as injection molded plastic such as a
polycarbonate material, while torsion bars 306 are preferably made
of a material having properties and/or dimensions so as to be
flexible or twistable about their longitudinal axis, e.g.,
stainless steel bars having a thickness in the range from about 50
to 75 .mu.m and a width in the range from about 0.5 to 1 mm. Each
integrated biosensor devices 304 is operatively attached to a
torsion bar 306, preferably wherein there is a one-to-one
correspondence between devices 304 and torsion bars 306. Each
torsion bar 306 allows the corresponding attached device to rotate
relative to frame 304 at least partially about the longitudinal
axis defined by the torsion bar. As such, this axis of rotation is
perpendicular to a path along which cartridge 300 is caused to
rotate or travel. Cartridge 300 typically has a diameter ranging
from about 3 to 4 cm, where the distance between the center of the
disk and the biosensor devices typically ranges from about 7 to 9
mm.
[0061] As mentioned above, cartridge device 300 may further include
a drive wheel 308 for attachment to a drive shaft housed within
system 200 in which the cartridge device 300 is to be loaded.
Alternatively, drive wheel 308 may also be separately housed within
the system housing and be configured to receive and engage with
cartridge frame 302. Drive wheel 308 includes a hub 310 and a
plurality of frame bars 312 fixed to inner frame ring 302b.
Rotation of drive wheel 308 causes rotational translation of
cartridge body 302 and, thus, rotational translation of devices 304
about hub 310.
[0062] FIG. 7B illustrates a cut-away portion of cartridge device
300 operatively positioned within a bottom housing portion 314 of a
subject system having an aperture 316. The width of aperture 316 is
sufficient for the biosensor devices 316 to pass through, and
typically ranges from about 3 to 8 mm and usually from about 4 to 6
mm. Components 320a and 320b of a biosensor movement means are
operatively fixed within the system housing and located proximate a
forward side 318a and a reverse side 318b of aperture 316,
respectively. Component 320a has a wedged configuration and
component 320b has a spring-loaded clip configuration. As best seen
in FIGS. 8A-F, biosensor movement component 320a has a top planar
surface 322 and a downward sloping front surface 324, while
biosensor movement component 320b has a top clip member 326
spring-loaded or biased against a bottom clip member 328. Component
320a is positioned on bottom housing portion 314 and under
cartridge device 300 while component 320b is positioned such that
the plane in which cartridge device 300 and biosensor devices 304
rotate passes between clip members 326 and 328.
[0063] The movement undergone by a biosensor 304a throughout an
assay application is now described with reference to FIGS. 8A-F.
Cartridge device 300, when inactive, is preferably positioned such
that aperture 316 is free and clear of biosensor devices 304 so as
to prevent contamination of the biosensor devices and inadvertent
injury to the user. Furthermore, each device 304 is maintained in a
substantially planar position relative to bottom housing portion
314 by means of the tension placed on the devices 304 by torsion
bars 306. Advancing or rotating cartridge device in the direction
of arrow 330, ie., in a counter clockwise direction with reference
to FIG. 7B, will cause biosensor device 304a to advance or rotate
in the same direction thereby approaching component 320b. As device
304a is advanced, it is caused to wedge between top clip 326 and
bottom clip 328b (see FIG. 8A). As the clip members are biased
against each other, biosensor device 304a is in frictional contact
with component 320b when positioned between the clip members 326
and 328. When biosensor device 304a is sufficiently advanced in the
direction of arrow 332 such that its back or proximal end 334 is
between clip members 326 and 328, component 320b places a slight
upward force or pressure on biosensor device 304a thereby causing
device 304a to rotate about torsion bar 306 and front or needle end
336 of device 304a to deflect downward toward aperture 316 (see
FIG. 8B). As device 304a is advanced further forward, in the
direction of arrow 338, deflected front end 336 is caused to
contact sloped front surface 324 of wedged component 320a (see FIG.
8C), thereby being further forced or deflected in a downward and
forward direction. At this point, such deflection and forward
motion is sufficient to cause the skin-piercing element 340 of
device 304a to pierce the target skin surface of the user (not
shown). During such piercing, physiological fluid, e.g.,
interstitial fluid or blood, is accessed and drawn up into the
biosensor portion of device 304a for testing by the system's
measurement componentry. After sufficient time for accessing and
collecting a sample of physiological fluid has passed, the
cartridge device 300 is caused to move in a reverse direction 342,
e.g., in a clockwise direction, (see FIG. 8D) until device 304a
becomes disengaged from movement components 320a and 320b and is
caused by torsion bar 306 to return to its original planar position
relative to cartridge rings 302a and 302b (see FIG. 8E). Finally,
cartridge 300 is again advanced in a forward direction 346 until
used device 304a completely passes over aperture 316 of FIG. 7B
(see FIG. 8F), at which point cartridge 300 may be locked in place
so as to prevent inadvertent movement and possible injury to the
user. Such process is repeated with each device 304 when an assay
protocol is activated by the user. When all devices 304 are used,
ie., have been employed to perform an assay protocol, the used
cartridge may be removed from the system's housing and properly
disposed of. A replacement cartridge may then be loaded into the
system.
[0064] Referring now to FIGS. 9A-9G, there is shown another
embodiment of a biosensor movement means 400, particularly suited
for use with the biosensor/skin-piercing/access devices of FIG. 4.
The biosensor movement means 400 includes spaced-apart components
402a and 402b present within the housing of the subject systems.
Components 402a and 402b are spaced apart so as to straddle an
aperture 401 within the bottom housing wall, as described above,
and provide surfaces and edges to guide a biosensor device 404
through aperture 401 for operatively contacting a target skin
surface area of a user. Such surfaces and edges match the slope of
the surfaces and the angles of the edges of biosensor device 404.
More specifically, component 402a has an angled surface 410 that
matches the back surface 412 of angled biosensor device 404. Angled
surface 410 typically forms an angle a with the bottom surface 414
of component 402a that ranges from about 40.degree. to 55.degree.,
and more usually from about 45.degree. to 50.degree.. Furthermore,
component 402b has a top surface 406 that engages a bottom surface
408 of the angled biosensor device 404, and has an angled back
surface 416 that matches a front surface 418 of angled biosensor
device 404. Angled back surface 416 typically forms an angle .beta.
with the bottom surface 420 of component 402b that ranges from
about 30.degree. to 50.degree. and more usually from about
25.degree. to 35.degree..
[0065] The movement undergone by biosensor device 404 throughout an
assay application is now described with reference to FIGS. 9A-9G.
As with the embodiment described with respect to FIGS. 7A and 7B,
biosensor device 404 may be operatively attached to a cartridge
(not shown) by way of a tension bar (not shown) or by way of a
rotational pivot attachment to a hub/spoke (see FIGS. 10A-10C) such
that biosensor device 404 is held in an original biased position in
which bottom surface 408 of device 404 is flush with top surface
406 of component 402b. In FIG. 9A, angled biosensor 404 is moved in
a first direction according to arrow 422, across top surface 406 of
component 402b. FIG. 9B shows that as the angled biosensor 404 is
moved across the spacing between components 402a and 402b in the
direction of arrow 424, it drops down into the opening there
between, moving along sloped surface 410 of component 402a. At this
point, the direction of travel of angled biosensor 404 is reversed,
as shown in FIG. 9C, in the forward direction indicated by arrow
426. Because of the downward force applied by the cartridge, angled
biosensor 404 continues to move downward along sloped surface 410
such that bottom surface 408 of angled biosensor 404 becomes flush
with a targeted skin surface exposed through aperture 401.
Continued forward movement of angled sensor 10, in the direction of
arrow 428 (see FIG. 9D), brings front surface 418 of angled
biosensor 404 into contact with inversely sloped surface 416 of
component 402b. This contact forces biosensor 404 further downward
and into the skin surface to the target skin surface, causing the
skin-piercing configurations 430 of biosensor 404 to penetrate the
target skin surface to selected skin layer, e.g., the dermis,
epidermis, subdermis, etc., thereby accessing the physiological
fluid of interest, e.g., interstitial fluid or blood, which fills
the capillary flow path of biosensor 404.
[0066] Following sampling and fluid fill of the capillary flow path
of biosensor 404, biosensor 404 is again moved in the first
direction as shown in FIG. 9E according to arrow 432. Continued
movement of biosensor 404 in the first, reverse direction causes
removal of biosensor 404 from the skin surface/sampling site and
brings biosensor 404 up, out of the opening between components 402a
and 402b, as shown in FIG. 9F and indicated by arrow 434. Once the
angled sensor is brought out of the opening, as shown in FIG. 9G,
the fluid present in the biosensor chamber can be assayed. (Of
course, where desired the fluid can be assayed while the sensor is
still in situ, depending on the preferred sampling/measurement
protocol being employed.) Such process is repeated with each
biosensor device 404 when an assay protocol is activated by the
user. When all devices 404 are used, i.e., have been employed to
perform an assay protocol, the used cartridge may be removed from
the system's housing and properly disposed of. A replacement
cartridge may then be loaded into the system.
[0067] The cartridge movement means of the embodiment described
with respect to FIGS. 4 and 9 is further illustrated in terms of a
representative rotary cartridge device as shown in FIGS. 10A to
10C. In FIG. 10A, rotary or disk cartridge 440 includes 8
individual angled biosensors 442 and is positioned on top of bottom
surface 444 of housing (not shown) having an aperture 446 therein.
In use, cartridge 440 rotates in a first clockwise direction 448 as
shown in FIG. 10A to operatively position a biosensor 442 relative
to the biosensor movement means according to FIGS. 9A and 9B. The
direction of the cartridge rotation is then reversed to a
counter-clockwise direction 450 as shown in FIG. 10B, which brings
the biosensor 442a into the aperture 446 within bottom surface 444
wherein the target skin surface area is pierced and physiological
fluid is accessed an transported to the chamber of biosensor 442a.
Then, the direction of rotation of cartridge 440 is again reversed
to a clockwise direction 452 as shown in FIG. 10C, which withdraws
biosensor 442a out of the skin, followed by subsequent measurement
of analyte in the accessed fluid.
[0068] With minor modifications understood by those skilled in the
art, the biosensor configuration described above with respect to
FIG. 5 may be similarly employed with the cartridge embodiments of
FIGS. 7 and 8 or of FIGS. 9 and 10 and their respective cartridge
and biosensor movement means. As such, the cartridge as well as the
corresponding construct of the subject system may be configured in
a number of different ways, so long as the cartridge device can be
manipulated in a forward and reverse direction for performing the
assay protocol, and as along as the biosensor devices can be
operatively manipulated the biosensor movement means of the system
so that the biosensor devices present on the cartridge can pierce
the skin surface and access the physiological fluid therein.
[0069] The device and systems may take a variety of different
configurations. In certain embodiments, the devices are single
integral devices, in which the measurement means, processing means,
display means etc. are all present on the same structure. In yet
other embodiments, one or more of the components may be separate
from the other components. For example, the measurement means may
be separated from the display means, where telemetric communication
or analysis data transmission means, e.g., radio frequency or RF
means, are employed to provide for data communication between the
two or more disparate components of the device.
[0070] One representative subject system embodiment is a
"watchband" embodiment as shown in FIG. 11A, in which the device
500 is configured to be worn around a limbic portion 502, e.g., a
forearm, in a manner analogous to a watch. In this embodiment, all
of the components of the device may be present in one integral
unit, where the unit is maintained in contact with the skin of the
host via an adjustable strap 504 or other retention means.
[0071] Where it is desirable to have a subject system in contact
with a portion of the user that is not readily viewable, e.g., a
portion of the waste or other portion that is typically covered by
clothes or otherwise not readily viewable, a two component system,
as shown in FIG. 11B, may be employed. With such an embodiment, the
cartridge device and measurement means, i.e., the biosensors and
meter, are present within one component, e.g., a "waistband"
component 506, and the display and control means are present on a
second component of the system, e.g., a hand-held, remote control
unit 508. The two components communicate with each other a data
communication means, where the data communication means is
typically a wireless data communication means, e.g., RF telemetric
means.
[0072] In other embodiments of the present invention, the subject
systems do not require a band or strap for attachment, but instead,
may be attached to an appropriate skin area by means of a
biocompatible adhesive.
Methods of the Present Invention
[0073] The subject systems and devices find use in methods of
determining a characteristic of physiological fluid, most
typically, measuring the concentration of an analyte in a
physiological fluid. In practicing the subject methods, a device
having an integrated biosensor and skin-piercing element, such as
the various embodiments described above, is provided and positioned
relative to a target skin surface area of the user. The integrated
biosensor device is caused to move or translate from an initial or
retracted position to a second, extended or skin-contacting
position skin wherein the target surface is pierced, and
physiological fluid is accessed and transported to the biosensor
portion of the device. The translation or movement of the device is
reversed to remove and retract it from the skin.
[0074] When used with the subject cartridge devices described
above, a plurality of such integrated biosensor devices is provided
in operative engagement with the cartridge device. The cartridge
device is provided and positioned planar to a target skin surface
area of the user. A movement means is employed to move or translate
the cartridge in a first direction which acts to move or translate
the biosensor device from an initial or retracted position to a
second, extended or skin-contacting position wherein the target
surface is pierced, physiological fluid is accessed and transported
to the biosensor portion of the device. The movement means is then
activated to move or translate the cartridge device in a second or
reverse direction which acts to move or translate the biosensor
from this second, extended position back to a retracted position.
Such movement of the biosensor device from a retracted to a
skin-contacting position, and visa versa, may be further defined by
deflecting the biosensor device from a substantially planar
position to angled or deflected position for contacting and
piercing the skin.
[0075] When used with the subject system as described above, the
cartridge device is provided within or loaded into a housing
structure having a skin-facing wall having an aperture therein. The
external surface of the skin-facing wall is preferably positioned
flush with the targeted skin surface area of the user. The
cartridge device is positioned within housing structure such that
it is planar with the skin facing surface and wherein the
translation of the plurality of biosensor devices is in a pathway
directly over the aperture. Upon movement or translation of the
cartridge as described above, the movement or deflection of a
particular biosensor device involves passage of at least the
skin-piercing element through the aperture to contact and pierce
the skin surface.
[0076] The subject methods further include providing a meter or
measurement means as described above in operative contact with the
biosensor device for measuring the selected characteristic of the
sampled physiological fluid transferred to the biosensor device
upon accessing the physiological fluid. Upon filling of the
reaction zone or matrix area of the biosensor device with the
sampled physiological fluid, a signal is applied to the biosensor
by the meter componentry of the subject system, and the chemical
characteristic of interest, e.g., analyte concentration, is made
and the resulting measurement data is displayed via a display
provided on the system housing and is stored into memory for
immediate or later retrieval.
[0077] The subject methods, devices and systems find use in a
variety of different applications in which detection of an analyte
and/or measurement of analyte concentration in a physiological
fluid is desired. The subject systems, devices and methods find
particular use in analyte concentration monitoring applications
over a given period of time, as described in copending U.S. patent
application Ser. No. 09/865,826, the disclosure of which is herein
incorporated by reference, where the physiological fluid
sampling/measurement occurs automatically and continuously
according to a predetermined schedule.
[0078] In these monitoring applications, the present invention may
be employed to: (a) continuously monitor an analyte whose
concentration is associated with a disease condition, e.g., hypo-or
hyperglycemia in blood sugar disorders such as diabetes; (b)
continuously monitor an analyte whose concentration is associated
with a non-disease physiological condition of interest, e.g.,
alcohol intoxication, illegal drug use; (c) continuously monitor
the concentration of a therapeutic agent in drug therapy
applications; etc.
[0079] Where the analyte is glucose, the present invention finds
use in a variety of different applications relating to the
treatment and management of glucose associated disease conditions,
e.g., diabetes and related conditions. In these embodiments, the
subject methods and devices find use in providing for "continual"
glucose monitoring, by which is meant that glucose levels in a
patient are measured intermittently and automatically according to
a predetermined schedule. The subject methods can also be employed
to detect and predict the occurrence of hypo- and hyperglycemic
conditions. In such applications, the pattern of continually
monitored analyte concentration measurements can be, employed to
determine whether a patient is experiencing hyper- or hypoglycemia
by comparing the pattern of measurement results stored within the
systems memory storage means to a control or reference pattern. In
addition, one can look at a pattern of measurements and compare it
to an appropriate control or reference pattern to predict the
occurrence of a hypo or hyperglycemic condition. The subject
methods can be part of a more comprehensive therapy protocol
designed to prevent the occurrence of hypo and hyperglycemic
events, e.g., by predicting the occurrence of such events with the
subject methods and device and intervening in blood sugar
metabolism in a manner that prevents the occurrence of the
predicted event.
[0080] The present invention may be employed with a variety of
different types of hosts where analyte monitoring is desired. Hosts
of interest include, but are not limited to mammals. Mammals of
interest include valuable livestock, e.g., horses, cows, sheeps,
etc., pets, e.g., dogs, cats etc., and humans. In most embodiments,
the mammals on which the subject methods are practiced are
humans.
Kits
[0081] Also provided are kits for practicing the subject methods.
In one embodiment, the kits include a system for practicing the
subject invention. The system may be a single integral device or
made up of two or more disparate components, e.g., a remote-control
and display component and a measurement component. The kits may
include a single disposable cartridge device, or two or more
disposable cartridges devices, as described above for use with the
subject system. Finally, the kits typically include instructions
for using the subject systems and for loading and removing
cartridges into and out of the subject system. These instructions
may be present on one or more of the packaging, a label insert,
containers present in the kits, and the like.
[0082] Although the foregoing invention has been described in some
detail by way of illustration and example for purposes of clarity
of understanding, it is readily apparent to those of ordinary skill
in the art in light of the teachings of this invention that certain
changes and modifications may be made thereto without departing
from the spirit or scope of the appended claims.
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