U.S. patent application number 10/914818 was filed with the patent office on 2005-01-13 for method and device for sampling and analyzing interstitial fluid and whole blood samples.
Invention is credited to Chambers, Garry, Chatelier, Ron, Hodges, Alastair.
Application Number | 20050010137 10/914818 |
Document ID | / |
Family ID | 24137712 |
Filed Date | 2005-01-13 |
United States Patent
Application |
20050010137 |
Kind Code |
A1 |
Hodges, Alastair ; et
al. |
January 13, 2005 |
Method and device for sampling and analyzing interstitial fluid and
whole blood samples
Abstract
The invention disclosed in this application is a method and
device for combining the sampling and analyzing of sub-dermal fluid
samples, e.g., interstitial fluid or whole blood, in a device
suitable for hospital bedside and home use. It is applicable to any
analyte that exists in a usefully representative concentration in
the fluid, and is especially suited to the monitoring of
glucose.
Inventors: |
Hodges, Alastair; (Blackburn
South, AU) ; Chatelier, Ron; (San Diego, CA) ;
Chambers, Garry; (San Diego, CA) |
Correspondence
Address: |
NUTTER MCCLENNEN & FISH LLP
WORLD TRADE CENTER WEST
155 SEAPORT BOULEVARD
BOSTON
MA
02210-2604
US
|
Family ID: |
24137712 |
Appl. No.: |
10/914818 |
Filed: |
August 10, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10914818 |
Aug 10, 2004 |
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10166487 |
Jun 10, 2002 |
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10166487 |
Jun 10, 2002 |
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09536235 |
Mar 27, 2000 |
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6612111 |
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Current U.S.
Class: |
600/583 ;
600/584; 604/309 |
Current CPC
Class: |
A61B 5/150022 20130101;
A61B 5/150503 20130101; A61B 5/15113 20130101; A61B 5/14532
20130101; A61B 5/150358 20130101; A61B 5/150389 20130101; A61B
5/150213 20130101; A61B 2562/0295 20130101; A61B 5/15105 20130101;
A61B 2010/008 20130101; A61B 5/15142 20130101; A61B 5/14865
20130101; A61B 5/14546 20130101; A61B 5/150221 20130101; A61B
5/1519 20130101; A61B 5/15117 20130101; A61B 5/14514 20130101; A61B
5/150755 20130101 |
Class at
Publication: |
600/583 ;
600/584; 604/309 |
International
Class: |
A61B 005/00 |
Claims
1. A fluid sampling device comprising a body, the body comprising a
dermal layer penetration probe having a penetrating end and a
communicating end, an analysis chamber having a proximal and distal
end, the analysis chamber having a volume, and a pre-chamber having
a volume and a first and second end, wherein the pre-chamber is
interposed between the penetration probe and the analysis chamber
such that the first end of the pre-chamber is adjacent the
communicating end of the penetration probe and the second end of
the pre-chamber is adjacent the proximal end of the analysis
chamber, wherein the penetration probe is in fluid communication
with the analysis chamber such that fluid can flow from the
penetration probe toward the analysis chamber, and wherein a
capillary force exerted by the analysis chamber is greater than a
capillary force exerted by the pre-chamber.
2.-54. Canceled
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a method and device for
combining the sampling and analyzing of interstitial fluid or whole
blood samples which is suitable for hospital beside and home
use.
BACKGROUND OF THE INVENTION
[0002] The management of many medical conditions requires the
measurement and monitoring of a variety of analytes in bodily
fluid. Historically, the measurement of analytes in blood has
required an invasive technique, such as a venipuncture or finger
puncture, to obtain blood for sampling purposes. An example of an
analyte which is routinely tested by obtaining a blood sample
through an invasive technique is glucose. In order to control their
condition, diabetics must monitor their glucose levels on a regular
basis. Invasive techniques used to obtain a blood sample for
analysis have the disadvantage of being painful, which can reduce
patient compliance in regular monitoring. Repeated testing, e.g.,
on a fingertip, can result in scar tissue build-up which makes
obtaining a sample in that region more difficult. Moreover,
invasive sampling procedures pose a risk of infection or disease
transmission.
[0003] An alternative is to sample interstitial fluid rather than
whole blood. Interstitial fluid is the fluid that fills the space
between the connective tissue and cells of the dermal layer of the
skin. An application where interstitial fluid has been shown to be
an appropriate sampling substitute for plasma or whole blood is in
the measurement of glucose concentration (J. Lab. Clin. Med. 1997,
130, 436-41).
[0004] In the patents U.S. Pat. No. 5,879,367, U.S. Pat. No.
5,879,310, U.S. Pat. No. 5,820,570 and U.S. Pat. No. 5,582,184 are
disclosed methods of sampling using a fine needle in conjunction
with a device to limit the penetration depth to obtain small
volumes of interstitial fluid for the purpose of glucose
monitoring. However, there is no method disclosed for analyzing the
drawn samples that is suitable for home use or hospital bedside
use.
SUMMARY OF THE INVENTION
[0005] It is desirable to be able to measure the concentration of
analytes in humans or other animals without having to draw a blood
sample by conventional methods. It is further desirable to be able
to do so with an inexpensive disposable device that is simple
enough for home or hospital bedside use.
[0006] The invention provides a suitable alternative to
conventional sampling devices and methods that is less invasive
than traditional whole blood sampling techniques and that requires
a considerably smaller sample volume than is required in the
conventional venipuncture or finger puncture sampling methods.
Because of the smaller sample volume required, a smaller wound is
necessary to obtain the sample. In the conventional finger stick
method, a drop of blood is formed on the tip of a finger, then the
sensor sample entrance is wetted with the drop. Because the sample
comes into contact with the skin surface, contamination of the
sample by material on the skin surface is possible. The devices and
methods disclosed herein do not require forming a blood drop on the
surface of the skin, and therefore have less risk of sample
contamination.
[0007] In one embodiment of the present invention, a fluid sampling
device is provided which includes a body, the body including a
dermal layer penetration probe having a penetrating end and a
communicating end, and an analysis chamber having a proximal and
distal end, the analysis chamber having a volume, wherein the
penetration probe is in fluid communication with the analysis
chamber such that fluid can flow from the penetration probe toward
the analysis chamber. The analysis chamber can have at least one
flexible wall which can be compressed to reduce the volume of the
analysis chamber. The penetration probe-can include, for example, a
needle, a lancet, a tube, a channel, or a solid protrusion and can
be constructed of a material such as carbon fiber, boron fiber,
plastic, metal, glass, ceramic, a composite material, mixtures
thereof, and combinations thereof. The penetration probe can
include two sheets of material in substantial registration, having
a protrusion on each sheet, wherein the sheets are spaced apart
such that liquid can be drawn between the sheets by capillary
action. The two sheets of material can extend into the device so as
to form a pre-chamber. The penetration probe can be positioned
within a recess in the proximal end of the device, and the recess
can be configured to substantially align with a shape of a selected
dermal surface.
[0008] In a further embodiment, the device can further include a
pre-chamber having a volume and a first and second end, wherein the
pre-chamber is interposed between the penetration probe and the
analysis chamber such that the first end of the pre-chamber is
adjacent the communicating end of the penetration probe and the
second end of the pre-chamber is adjacent the proximal end of the
analysis chamber. The volume of the pre-chamber can be greater than
or equal to the volume of the analysis chamber. The pre-chamber can
have at least one flexible wall that can be compressed to reduce
the volume of the pre-chamber. The pre-chamber can also include a
valve at the first end capable of substantially sealing the
pre-chamber from the penetration probe.
[0009] In another embodiment, the device further includes a
compressible bladder in communication with the analysis chamber,
the compressible bladder being capable of applying a positive or a
negative pressure to the analysis chamber.
[0010] In yet another embodiment, the pre-chamber and the analysis
chamber can be capable of exerting different capillary forces. The
capillary force exerted by the analysis chamber can be greater than
the capillary force exerted by the pre-chamber. The differential
capillary force can be derived, at least in part, from a difference
between the pre-chamber height and the analysis chamber height. In
this embodiment, the interior surface of the pre-chamber can
include at least first and second pre-chamber walls spaced apart at
a first distance to define a pre-chamber height, and the interior
surface of the analysis chamber can include at least first and
second analysis chamber walls spaced apart at a second distance to
define an analysis chamber height, wherein the height of the
analysis chamber is less than the height of the pre-chamber.
[0011] In yet another further embodiment, at least one of the
chambers can include a substance capable of enhancing or
diminishing the capillary force exerted by the chamber. The
substance can include, for example, a polymer, a resin, a powder, a
mesh, a fibrous material, a crystalline material, or a porous
material. Suitable substances include polyethylene glycol,
polyvinylpyrrolidone, a surfactant, a hydrophilic block copolymer,
and polyvinylacetate.
[0012] In a further embodiment, the device further includes a
releasable actuator capable of supplying a force sufficient to
cause the penetration probe to penetrate a dermal layer. The
actuator can be external to or integral with the body, and upon
release propels the body toward the dermal layer.
[0013] In a further embodiment, the analysis chamber can include an
electrochemical cell including a working electrode and a
counter/reference electrode and an interface for communication with
a meter, wherein the interface communicates a voltage or a
current.
[0014] In yet another embodiment of the present invention, a method
for determining a presence or an absence of an analyte in a fluid
sample is provided including the steps of providing a fluid
sampling device as described above; penetrating a dermal layer with
the penetration probe; substantially filling the analysis chamber
with a fluid sample by allowing the sample to flow from the
penetration probe toward the analysis chamber; and detecting a
presence or an absence of the analyte within the analysis chamber.
The sample can include, for example, interstitial fluid and whole
blood. A qualitative or quantitative measurement of a
characteristic of the sample can be obtained in the detecting step.
The characteristic of the sample can include, for example, a
reaction product of the analyte, such as a color indicator, an
electric current, an electric potential, an acid, a base, a reduced
species, a precipitate, and a gas. The analyte can include, for
example, an ion such as potassium, an element, a sugar, an alcohol
such as ethanol, a hormone, a protein, an enzyme, a cofactor, a
nucleic acid sequence, a lipid, a pharmaceutical, and a drug.
Cholesterol and lactate are examples of substances that can be
analyzed.
[0015] In a further embodiment, the flow of sample toward the
analysis chamber can be driven by a driving force, e.g., capillary
force or a pressure differential. Where the analysis chamber has a
flexible wall, the wall can be compressed to reduce the volume of
the analysis chamber prior to penetrating the dermal, then the
compression released to form a partial vacuum in the analysis
chamber. Where the fluid sampling device further includes a
compressible bladder, the bladder can be compressed to reduce its
volume, then after penetration of the dermal layer the compression
can be released to form a partial vacuum in the compressible
bladder and analysis chamber.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 shows a top view (not to scale) of one embodiment of
a sampling device illustrating an arrangement of the penetration
probe, pre-chamber, and analysis chamber.
[0017] FIG. 2 shows a cross section (not to scale) along the line
A-A' of FIG. 1.
[0018] FIG. 3 shows a top view (not to scale) of one embodiment of
a sampling device illustrating an arrangement of the penetration
probe, pre-chamber, and analysis chamber wherein the proximal edge
of the device forms a recess.
[0019] FIG. 4 shows a top view (not to scale) of one embodiment of
a sampling device illustrating an arrangement of the penetration
probe, pre-chamber, and analysis chamber.
[0020] FIG. 5 shows a cross section (not to scale) along the line
B-B' of FIG. 4.
[0021] FIGS. 6a and 6b (not to scale) depict an embodiment of the
invention wherein the device is loaded in a releasable actuator to
facilitate penetration of a dermal layer by the penetration probe.
FIG. 6a depicts the device loaded in the actuator, wherein the
actuator is in the cocked position, ready to be triggered. FIG. 6b
depicts the device and actuator after triggering.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0022] Introduction
[0023] The following description and examples illustrate various
embodiments of the present invention in detail. Those of skill in
the art will recognize that there are numerous variations and
modifications of this invention that are encompassed by its scope.
Accordingly, the description of a preferred embodiment should not
be deemed to limit the scope of the present invention. Methods and
devices for optimizing sampling of fluid samples are discussed
further in copending U.S. patent application no ______, filed on
even date herewith, entitled "METHOD OF PREVENTING SHORT SAMPLING
OF A CAPILLARY OR WICKING FILL DEVICE," which is incorporated
herein by reference in its entirety.
[0024] The invention disclosed in this application is a method and
device for combining the sampling and analyzing of a fluid sample
from sub-dermal tissue in a device suitable for hospital bedside
and home use. The fluid sample can comprise, but is not limited to,
interstitial fluid or whole blood samples obtained from an animal.
Any fluid sample obtained from sub-dermal tissue of a plant or an
animal can sampled and analyzed, thus the invention has broad
application in the fields of human medicine, veterinary medicine,
and horticultural science. The device and method are applicable to
any analyte that exists in a usefully representative concentration
in the fluid sample. For clarity, the present disclosure will
discuss the application to glucose monitoring. However, it is to be
understood that the invention is not limited to the monitoring of
glucose, and that other analytes, as discussed below, can also be
measured.
[0025] The method utilizes an integrated sampling and analyzing
device 10 incorporating a penetration probe 12 capable of
penetrating a patient's dermal layers to extract an interstitial
fluid or whole blood sample, and a method for transferring the
sample from the penetration probe 12 to analysis chamber 20. In one
embodiment, the device 12 can be a one-shot disposable device which
can be inserted into a meter which communicates with the analysis
chamber 20 to perform the analysis of the sample and present and
optionally store the result.
[0026] In the device 10, a penetration probe 12 for penetrating the
subject's dermal layers to collect an interstitial fluid or whole
blood sample is integrated with an analysis chamber 20. A property
of sampling interstitial fluid is that it can take from several to
tens of seconds to collect sufficient sample to analyze. This is
often not desirable for an analysis chamber 20 wherein the analyte
undergoes a reaction as part of the analysis process, as it can be
difficult to obtain an accurate start time for the test as well as
achieve an even reacting reagent distribution in the sample. In a
second aspect of the current invention a method is disclosed for
collecting the sample in a pre-chamber 14 and, when full,
transferring the sample quickly to an analysis chamber 20.
[0027] In this disclosure, unless a different meaning is clear from
the context of its usage, "proximal" refers to a region or
structure of the device situated toward or adjacent to the dermal
surface to be penetrated, and "distal" refers a region or structure
of the device situated toward the opposite (non-proximal) end of
the device. For example, the penetration probe 12 is at the
proximal end of the device.
[0028] The Penetration Probe
[0029] The penetration probe 12 can be any device capable of
penetrating the patient's dermal layers to the desired extent and
capable of transporting a sample to a pre-chamber 14 or analysis
chamber 20. The penetration probe 12 comprises two ends, as
illustrated in FIG. 1. The penetrating end 11 of the penetration
probe 12 is the end inserted into the dermal layer. The
communicating end 13 of the penetration probe 12 is the end which
is in communication with either the pre-chamber 14 or the analysis
chamber 20.
[0030] One or more protrusions 12 with at least one sharp edge or
point are suitable as the penetration probe 12. The penetration
probe 12 can be fabricated from materials including plastic, metal,
glass, ceramic, a composite material (e.g., a composite of ceramic
and metal particles), or mixtures and combinations of these
materials. The penetration probe 12 can be in the form of a solid
protrusion, a needle, a lancet, a tube or a channel. The channel
can optionally be open along one or more of its elongated sides. As
illustrated in FIG. 2, a preferred embodiment of the penetration
probe 12 is two sheets 30 of material formed so as to have a
sharply pointed protrusion 12 on each sheet 30 in substantial
registration, with the sheets 30 spaced apart such that liquid can
be drawn between the sheets 30 by capillary action. In a
particularly preferred embodiment, the two sheets 30 of material
extend to and overlap with the analysis chamber 20 to form a
pre-chamber 14 for sample collection.
[0031] When interstitial fluid is sampled, the penetration depth
can be controlled by limiting the length the penetration probe 12
protrudes from the proximal surface 34 of the sampling device 10 to
less than the thickness of the dermal layer. In a preferred
embodiment, the length of the protrusion 12 will be less than 2 to
3 mm, more preferably about 1.5 mm. After penetration to a suitable
depth corresponding to the length of the protrusion 12, contact
between the surface of the dermal layer and the surface 34 of the
analyzing device prevents further penetration. For other uses, such
as in sampling interstitial fluid from regions having a thick
dermal layer, or for veterinary uses, it can be desirable for the
length of the protrusion 12 to be greater than 3 mm. Accordingly,
the invention contemplates protrusions 12 of any length, wherein
the length is sufficient to sample interstitial fluid. When whole
blood is sampled, a slightly longer penetration probe 12 should be
used, i.e., one having a length greater than 2 to 3 mm.
[0032] The diameter or width of the penetration probe 12 depends
upon the design of the penetration probe 12. Suitable diameters or
widths are those which provide sufficient sample flow. In the case
of a protrusion 12 forming a sharp edge or point, or a tube or
channel, the minimum diameter or width is typically greater than
about 10 .mu.m. When the penetrating means 12 comprises two sheets
30 in substantial registration, each having a sharply pointed
protrusion 12, the two protrusions 12 are typically spaced from 1
mm to 10 .mu.m apart.
[0033] The penetration probe 12 can be located on any suitable part
of the test strip 10, i.e., an edge 34, a corner 42, or one of the
flat surfaces 44. Protection can be provided to the penetration
probe 12 by locating it within a recess formed in the distal edge
34 of the test strip 10, as shown in FIG. 3, or in a depression on
the surface 44 of the test strip 10. In a preferred embodiment, the
recess in the distal edge 34 of the test strip 10 can be configured
to substantially align with the shape of a selected dermal surface,
e.g., a fingertip. However, the recess can be configured in other
suitable shapes, e.g., a square recess, a V-shaped recess, a curved
recess, a polygonal recess, and the like. In a preferred
embodiment, the penetration probe 12 does not protrude past the
proximal-most portion of the proximal edge 34 or surface 44 of the
device 10, but when pressed against the skin, the skin deforms into
the recess and is punctured by the penetration probe 12. Such an
arrangement aids sampling by compressing the area of the skin
around the sampling point. The penetration probe 12 can form an
integral part of another component of the test strip 10, e.g., a
side of the pre-chamber 54, as shown in FIG. 2. Alternatively, the
penetration probe 12 can comprise a separate part which is attached
to or incorporated into the test strip 10 by any suitable means,
e.g., adhesive, thermal bonding, interlocking parts, pressure, and
the like. The penetration probe 12 can be retractable or
non-retractable.
[0034] Penetration itself can be accomplished by any suitable
means, including inserting the penetration device 12 manually or by
means of a releasable actuator 84 such as, for example, a
spring-loaded mechanism 84 as depicted in FIGS. 6a and 6b. Such a
spring-loaded mechanism 84 incorporates a spring 86 which is
compressed and held in place by a trigger 88 which can release the
force compressing the spring 86 when the triggering mechanism is
activated. The trigger 88 can be activated manually, or the device
84 can incorporate a pressure sensor which indicates that
sufficient pressure has been applied to obtain the sample, thereby
activating the trigger 88. In one embodiment, the distal end of the
device 10 is placed in the spring-loaded mechanism 84 such that
when the force compressing the spring 86 is released by activating
the trigger 88, force is transferred to the device 10, which is
ejected from the mechanism 84, thereby inserting the penetrating
probe 12 into the dermal layer.
[0035] Any suitable body part can be used for sampling. In a
preferred embodiment, the sampling area is one which does not have
a high density of nerve endings, e.g., the forearm. Typically, 5 to
15 seconds is required to obtain sufficient sample. Application of
pressure to the sampling area can be needed to extract interstitial
fluid or whole blood. To facilitate the appropriate amount of
pressure being applied, a pressure sensor can be incorporated into
the device 10 which indicates when sufficient pressure has been
applied. Sample acquisition time can be improved by applying
increased pressure to the area surrounding the direct sampling
area. Some of the factors that can affect interstitial fluid or
whole blood sample acquisition include the patient's age, skin
thickness, temperature, and hydration. The amount of interstitial
or whole blood sample collected for testing can preferably be about
0.02 .mu.l or greater, more preferably 0.1 .mu.l or greater, and
most preferably about 0.5 .mu.l or greater.
[0036] In one preferred embodiment, the device 10 can be inserted
into a meter prior to sample acquisition. In such an embodiment,
the meter serves multiple functions, including supporting the
device 10, providing an automated means of initiating sample
acquisition, and indicating when sample acquisition is
complete.
[0037] Transfer of Sample from Penetration probe to Analysis
Chamber
[0038] In a preferred embodiment of the sampling device 10, the
device comprises two parts--the penetration probe 12 and an
analysis chamber 20. In another preferred embodiment, illustrated
in FIGS. 1 and 2, the device 10 comprises the penetration probe 12
and a pre-chamber 14. The pre-chamber 14 can then be integrated
with or can be interfaced to the analysis chamber 20.
[0039] In a further embodiment, the analysis chamber 20 is
integrated with or can be interfaced to a means for facilitating
filling of the analysis chamber 20. This means can comprise a
collapsible or compressible bladder 22, as shown in FIGS. 3 and 4,
which can be used to apply a positive or negative pressure (i.e.,
partial vacuum) to the analysis chamber 20. The compressible
bladder 22 can comprise any chamber with flexible walls that can be
compressed to reduce the volume of the chamber. When the force
compressing the compressible bladder 22 is released, a partial
vacuum is formed which draws sample into the analysis chamber 20.
In a preferred embodiment, the volume of the compressible bladder
22 is sufficiently large so that when the bladder 22 is
substantially fully compressed, the reduction in volume of the
bladder 22 is larger than or equal to the total volume of the
analysis chamber 20, thereby ensuring that the analysis chamber 20
is substantially filled. However, a compressible bladder 22 with a
smaller volume than the analysis chamber 20 can also be effective
in assisting the filling of the analysis chamber 20.
[0040] Alternatively, the analysis chamber 20 itself can be
collapsible or compressible. In such an embodiment, a piston or
other compressing agent, such as a patient's or clinician's
fingers, can first compress then release the analysis chamber 20,
thereby forming a partial vacuum. When the compressing force is
released, the partial vacuum causes the sample to flow from the
penetration probe toward the analysis chamber.
[0041] Pre-chamber
[0042] In a preferred embodiment, as illustrated in FIGS. 1 and 2,
a pre-chamber 14 is provided in the integrated sampling and testing
device 10 for accumulation and storage of the collected sample
prior to its being transferred to the analysis chamber 20. A
pre-chamber 14 is useful when using an analysis method which
requires that the sample fill the analysis chamber 20 in a short
period of time to return accurate results, i.e., a time shorter
than that required to draw sufficient sample from the dermal layer.
In a preferred embodiment, the volume of the pre-chamber 14 is
larger than that of the analysis chamber 20, thus ensuring that
once the pre-chamber 14 is filled, sufficient sample has been
collected to completely fill the analysis chamber 20.
[0043] In a preferred embodiment, as illustrated in FIGS. 1 and 2,
the penetration probe 12 opens into the pre-chamber 14 at a first
end, and at the second end the pre-chamber 14 opens to the analysis
chamber 20. The pre-chamber 14 can be free of reagents or other
substances, or can optionally contain one or more substances to
enhance or diminish the capillary force exerted by the walls of the
pre-chamber 14 or to pre-treat the sample prior to analysis. These
substances can include, for example, polymers, resins, powders,
meshes, fibrous materials, crystalline materials, porous materials,
or a mixture or combination thereof. To facilitate effective
filling of the analysis chamber 20, a preferred embodiment utilizes
a pre-chamber 14 and analysis chamber 20 of different heights, as
shown in FIG. 2. Where the analysis chamber 20 is formed so that
its height (typically referring to the smallest chamber dimension)
is smaller than the height of the pre-chamber 14, a capillary force
is generated that is capable of drawing fluid out of the
pre-chamber 14 and into the analysis chamber 20. A first air vent
64 can be formed at the end 70 of the analysis chamber 20 opposite
the opening 62 to the pre-chamber 14, facilitating the filling of
the analysis chamber 20 by allowing air to be displaced from the
analysis chamber 20 as sample enters. Optionally, a second vent 74
can be formed opening into the pre-chamber 14 at the substantially
opposite end 60 of the pre-chamber 14 to where the penetration
probe 12 opens into the pre-chamber 14. This vent 74 provides air
to the pre-chamber 14 to replace the sample as it is transferred
from the pre-chamber 14 to the analysis chamber 20. The vent 74 can
be placed in any suitable position on the test strip 10. In a
preferred embodiment, the vent 74 incorporates a sharp corner,
e.g., at a 90.degree. angle, which functions as a "capillary stop"
to prevent sample from exiting the device 10 through the vent
74.
[0044] In another embodiment, the pre-chamber 14 consists of a
tube, or other shaped chamber, with flexible walls, attached to the
penetration probe 12. In this embodiment, the pre-chamber 14 is
either permanently fixed to the analysis chamber 20 or is placed
next to and aligned with a port to the analysis chamber 20. Such
alignment can occur during use by suitable placement in an external
device such as the measurement meter.
[0045] In one aspect of this embodiment, the pre-chamber 14 further
comprises a valve, defined as a device to control the flow of fluid
sample between the penetration probe 12 and the pre-chamber 14. The
valve can comprise one or more rollers, pistons, or squeezing
devices capable of simultaneously closing off the first end 60 of
the pre-chamber 14, and compressing the pre-chamber 14 such that
the fluid in the pre-chamber 14 is forced towards the second end 62
of the pre-chamber 14 and subsequently into the analysis chamber
20.
[0046] Alternatively, the analysis chamber 20 consists of a tube,
or other shaped chamber, with flexible walls, attached to the
penetration probe 12. In one aspect of this embodiment, the
analysis chamber 20, prior to penetration, is compressed by one or
more rollers, pistons, or other squeezing devices. After the
penetration probe 12 is inserted, the compression is released,
forming a vacuum which pulls sample into the analysis chamber 20.
In such an embodiment, the pre-chamber 14 can not be necessary if
sufficient vacuum is generated for rapid sample acquisition. In
such an embodiment, the device 10 can not require a vent 64, 74 if
such would interfere with forming a vacuum.
[0047] In another embodiment, illustrated in FIGS. 3 and 4, a
pre-chamber 14 of suitable size is formed which opens to the
penetration probe 12 on one end 60 and to the analysis chamber 20
on the other end 62. The end 70 of the analysis chamber 20 opposite
to that opening to the pre-chamber 14 opens to a compressible
bladder 22. The bladder 22 can be formed separately and attached to
the end 70 of the analysis chamber 20. Alternatively, it can be
formed by removing a section on the middle laminate 82 in the test
strip 10, similar to those described in WO97/00441 (incorporated
herein by reference in its entirety), as illustrated in FIGS. 3 and
4.
[0048] In use, the bladder 22 in the strip 10 is compressed by
suitable means prior to the penetration probe 12 being inserted
into the patient. Insertion of the penetration probe 12 can be
confirmed by use of a sensor, such as a pressure sensor, or the
patient can confirm that the penetration probe 12 is inserted
either visually or by touch. In the latter case, the patient
sensing can signal the meter, such as by pushing a button. At this
point, the means compressing the bladder 22 is withdrawn to a
halfway position to draw sample into the pre-chamber 14. When the
pre-chamber 14 is full, as indicated by a suitable sensor, the
meter indicates to the patient to withdraw the penetration probe
12. The compressing means then moves to its fully withdrawn
position and so draws the sample from the pre-chamber 14 into the
analysis chamber 20. In the case where the initial suction from the
bladder 22 causes the sample to be accumulated with sufficient
speed, the pre-chamber 14 can be dispensed with and the bladder 22
used to draw sample through the penetration probe 12 directly into
the analysis chamber 20. A vent 64, 74 which would interfere with
forming a vacuum need not be incorporated into the device in some
embodiments.
[0049] Analysis Chamber
[0050] In a preferred embodiment, the analysis chamber 20 is
contained in an analyzing device 10 comprising a disposable
analysis strip similar to that disclosed in WO97/00441. The
analysis strip of WO97/00441 contains a biosensor for determining
the concentration of an analyte in a carrier, e.g., the
concentration of glucose in a fluid sample. The electrochemical
analysis cell 20 in this strip has an effective volume of 1.5 .mu.l
or less, and can comprise a porous membrane, a working electrode on
one side of the membrane, and a counter/reference electrode on the
other side. In a preferred embodiment, an analysis cell 20 having
an effective volume of about 0.02 .mu.l or greater is used. More
preferably, the cell 20 has a volume ranging from about 0.1 P to
about 0.5 .mu.l.
[0051] In one aspect of this embodiment, the penetration probe 12
is a small needle integrated into the analysis strip 10 by being
inserted through a wall of the analysis chamber 20 such that one
end of the needle 12 opens into the strip analysis chamber 20. In
using a device 10 having this arrangement to obtain and analyze a
sample of interstitial fluid, the needle 12 is inserted into the
patient's dermal layer and sample is drawn into the needle 12 via
capillary action. The sample is then transferred from the needle 12
into the analysis chamber 20 by capillary action whereupon the
sample is analyzed. An opening 64 in the analysis chamber 20 to
atmosphere, remote from the point where the needle 12 opens into
the chamber, acts as a vent 64 to allow the escape of displaced air
as the analysis chamber 20 fills with sample. Analysis devices of
the type disclosed in WO97/00441 are particularly suited for use
with this arrangement because of their ability to utilize the very
small volumes of sample typically available with interstitial fluid
sampling.
[0052] The analysis chamber 20 can contain one or more substances
to enhance or diminish the capillary force exerted by the walls of
analysis chamber 20. Such materials can include polymers, resins,
powders, meshes, fibrous materials, crystalline materials, porous
materials, or a mixture or combination thereof, as can also be used
in the pre-chamber, discussed above. For example, the walls 24 of
the analysis chamber 20 can be coated with a hydrophilic material
to encourage the flow of fluid sample into the analysis chamber.
Suitable hydrophilic materials include polyethylene glycol,
polyvinylpyrrolidone, a surfactant, a hydrophilic block copolymer,
and polyacrylic acid. The analysis chamber 20 can also contain
reagents capable of reacting with the analyte or other substances
present in the sample. Such other substances can include substances
which interfere in determining the presence or absence of the
analyte. In such cases, the reagent will react with the substance
so that it no longer interferes with the analysis.
[0053] Any analyte present in a fluid sample in a detectable amount
can be analyzed using the device 10. A typical analytes can
include, but is not limited to, an ion, an element, a sugar, an
alcohol, a hormone, a protein, an enzyme, a cofactor, a nucleic
acid sequence, a lipid, and a drug. In a preferred embodiment,
glucose is the analyte to be tested. Typical analytes could
include, but are not limited to, ethanol, potassium ion,
pharmaceuticals, drugs, cholesterol, and lactate.
[0054] The presence or absence of the analyte can be determined
directly. Alternatively, the analyte can be determined by reacting
the analyte with one or more reagents present in the analysis
chamber. The product of that reaction, indicative of the presence
or absence of the analyte, would then be detected. Suitable
reaction products include, but are not limited to, a color
indicator, an electric current, an electric potential, an acid, a
base, a precipitate, or a gas.
[0055] Any suitable analytical method can be used for determining
the presence or absence of the analyte or a reaction product of the
analyte. Suitable analytical methods include, but are not limited
to, electrochemical methods, photoabsorption detection methods,
photoemission detection methods, and the measurement of magnetic
susceptibility. In the case of a reaction product having a
different color than the analyte, or the formation of a precipitate
or a gas, a visual determination can be a suitable method for
determining the presence or absence of the analyte.
[0056] Display/Storage of Measurement Data
[0057] In a preferred embodiment, an analysis strip as described
above or another embodiment of the sampling device 10 is integrated
with a measuring device, e.g., a meter, which can display, store or
record test data, optionally in computer-readable format. In such
an embodiment, the test strip 10 comprises an interface for
communicating with the meter, e.g., conductive leads from the
electrodes of the electrochemical cell 20. In the case of obtaining
an electrochemical measurement, the interface communicates a
voltage or a current to the electrochemical cell 20.
[0058] The above description discloses several methods and
materials of the present invention. This invention is susceptible
to modifications in the methods and materials, as well as
alterations in the fabrication methods and equipment. Such
modifications will become apparent to those skilled in the art from
a consideration of this disclosure or practice of the invention
disclosed herein. Consequently, it is not intended that this
invention be limited to the specific embodiments disclosed herein,
but that it cover all modifications and alternatives coming within
the true scope and spirit of the invention as embodied in the
attached claims.
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