U.S. patent application number 12/136154 was filed with the patent office on 2008-10-09 for diagnostic device.
This patent application is currently assigned to Kimberly-Clark Worldwide, Inc.. Invention is credited to Rosann Marie Kaylor, Robert John Lyng, Stephen Quirk.
Application Number | 20080248517 12/136154 |
Document ID | / |
Family ID | 21832808 |
Filed Date | 2008-10-09 |
United States Patent
Application |
20080248517 |
Kind Code |
A1 |
Quirk; Stephen ; et
al. |
October 9, 2008 |
Diagnostic Device
Abstract
Diagnostic devices for detecting the presence of an analyte in a
sample are provided. Devices of the present invention comprise a
means for inducing a pressure differential on a sample to direct
the sample to a test surface. In one embodiment, the means for
inducing a pressure differential on a sample to direct the sample
to a test surface comprises a syringe that can be used to draw a
sample from an opening to a test surface. In other embodiments, the
device also provides means for diluting a sample. In yet other
embodiments, the device also provides a means
Inventors: |
Quirk; Stephen; (Alpharetta,
GA) ; Lyng; Robert John; (Norcross, CA) ;
Kaylor; Rosann Marie; (Cumming, GA) |
Correspondence
Address: |
DORITY & MANNING, P.A.
POST OFFICE BOX 1449
GREENVILLE
SC
29602-1449
US
|
Assignee: |
Kimberly-Clark Worldwide,
Inc.
Neenah
WI
|
Family ID: |
21832808 |
Appl. No.: |
12/136154 |
Filed: |
June 10, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10026610 |
Dec 21, 2001 |
7384598 |
|
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12136154 |
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Current U.S.
Class: |
435/30 ;
73/864.83 |
Current CPC
Class: |
G01N 21/4788 20130101;
Y10T 436/2575 20150115 |
Class at
Publication: |
435/30 ;
73/864.83 |
International
Class: |
C12Q 1/24 20060101
C12Q001/24; G01N 1/00 20060101 G01N001/00 |
Claims
1-34. (canceled)
35. A method for testing a sample comprising: introducing a sample
into the opening of a diagnostic device comprising a syringe having
a piston, the diagnostic device further comprising a test strip
removably attached to the diagnostic device housing, wherein the
test strip defines a test surface; inducing a first negative
pressure differential on the sample by engaging the syringe to
position the piston to a first indicator, the first indicator
positioned to correspond to a pressure differential that directs
the sample through a first channel and into a first chamber;
inducing a second negative pressure differential by engaging the
syringe to position the piston to a second indicator, the second
indicator positioned to correspond to a pressure differential that
directs the sample from the first chamber to the test surface and
thereafter removing an unreacted portion of the sample from the
test surface, through a second channel and into a second
chamber.
36. The method of claim 35, wherein the test surface is a
diffraction-based test surface.
37. The method of claim 36, wherein the device further comprises
diffraction-enhancing elements.
38. The method of claim 36, wherein the test surface is defined by
a polymer film or metal-coated polymer film.
39. The method of claim 35, wherein the second chamber has a volume
sufficient to contain the entire sample.
40. The method of claim 35, further comprising directing the sample
from the opening through a third channel and into a third chamber
located upstream of the first chamber, the third chamber in fluid
communication with the first channel.
41. The method of claim 40, wherein the third chamber comprises a
means for separating one or more components from the sample
comprising a filter, membrane, film, nonwoven, paper, precipitating
agent, cell lysing agent, or combination thereof.
42. The method of claim 41, wherein the means for separating one or
more components from the sample removes red blood cells from the
sample.
43. The method of claim 40, wherein the third chamber comprises a
means for diluting the sample comprising a diluent.
44. The method of claim 40, wherein the diagnostic device further
comprises a third indicator corresponding to a third piston
position that indicates the sample has reached the third
chamber.
45. The method of claim 35, further comprising applying the test
surface with an analyte-specific binder.
46. The method of claim 35, wherein the first channel is formed by
a capillary tube.
47. The method of claim 35, wherein the sample is blood.
48. A method for testing a sample comprising: introducing a sample
into the opening of a diagnostic device comprising a syringe having
a piston, the diagnostic device further comprising a test strip
wherein the test strip defines a test surface; inducing a first
negative pressure differential on the sample by engaging the
syringe to position the piston to a third indicator, the third
indicator positioned to correspond to a pressure differential that
directs the sample through a third channel and into a third
chamber; inducing a second negative pressure differential by
engaging the syringe to position the piston to a first indicator,
the first indicator positioned to correspond to a pressure
differential that directs the sample from a third chamber through a
first channel and into a first chamber; inducing a third negative
pressure differential by engaging the syringe to position the
piston to a second indicator, the second indicator positioned to
correspond to a pressure differential that directs the sample from
the first chamber to the test surface and thereafter removing an
unreacted portion of the sample from the test surface, through a
second channel and into a second chamber.
49. The method of claim 48, wherein the test strip is removably
attached to the diagnostic device housing.
50. The method of claim 48, wherein the test surface is a
diffraction-based test surface.
51. The method of claim 50, wherein the device further comprises
diffraction-enhancing elements.
52. The method of claim 50, wherein the test surface is defined by
a polymer film or metal-coated polymer film.
53. The method of claim 48, wherein the second chamber has a volume
sufficient to contain the entire sample.
54. The method of claim 48, wherein the third chamber comprises a
means for separating one or more components from the sample
comprising a filter, membrane, film, nonwoven, paper, precipitating
agent, cell lysing agent, or combination thereof.
55. The method of claim 54, wherein the means for separating one or
more components from the sample removes red blood cells from the
sample.
56. The method of claim 48, wherein the third chamber comprises a
means for diluting the sample comprising a diluent.
57. The method of claim 48, further comprising applying the test
surface with an analyte-specific binder.
58. The method of claim 48, wherein the sample is blood.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to diagnostic devices.
Particularly, the present invention relates to devices that
comprise a means for inducing a pressure differential on a sample
to direct the sample to a test surface.
BACKGROUND
[0002] Diagnostic devices are used to detect an analyte in a
sample. The present invention relates to diagnostic devices and
methods. In one particular embodiment, the present invention
relates to diffraction-based diagnostic devices that can be used to
detect one or more analytes present in a medium by detecting
diffraction of an analyte/binder complex. These diffraction-based
devices comprise a surface upon which is printed in a pattern a
binder. Upon attachment of analyte to the binder that is printed in
a pattern on the surface, diffraction of light that is transmitted
through or reflected off of the printed surface occurs via the
physical dimensions and defined placement of the binder.
[0003] U.S. Pat. No. 4,992,385 to Godfrey, et al. describes a
method of preparing a diffraction grating from a thin polymer film
for subsequent use as a sensing device. The sensing device
described in U.S. Pat. No. 4,992,385 requires the use of a
spectrophotometric technique to detect changes in the device's
optical properties due to analyte binding. The device and method
described in U.S. Pat. No. 4,992,385 require a complex detection
method to detect changes in the diffraction pattern because changes
in a diffraction pattern are more subtle than the qualitative
determination that is made to determine whether a diffraction image
is formed or is not formed.
[0004] U.S. Pat. No. 5,196,350 to Backman et al. describes an
optical detection method for detecting the presence of specific
ligands. The method described in U.S. Pat. No. 5,196,350 is an
optical detection method for detecting specific ligands that
requires a mask comprising slits to produce a diffraction pattern.
An immunoassay device is placed between the mask and light source,
so that binding by an analyte causes a change in the diffraction or
interference pattern caused by the mask. Again, this method also
requires a complex detection method to detect changes in a
diffraction pattern and confirm the presence of a ligand.
[0005] International Publication No. WO 94/13835 describes a method
and a system to detect biological macromolecules via diffraction of
light from a probe of predetermined dimensions that diffracts light
in a known pattern. The probe comprises an active surface that is
able to highly concentrate the macromolecules relative to their
concentration in the sample solution. The method and the system
described in WO 94/13835 also require the use of a complex detector
and an analyzer in order to detect changes in the diffraction
pattern produced by the probe.
[0006] U.S. Pat. No. 6,261,519 describes a diagnostic device for
measuring the concentration of an analyte in a sample. The device
comprises sample port at one end for introducing a sample. The
device also comprises a bladder at the other end that must be
depressed, inserted into a liquid sample and released to draw a
sample. The device described in U.S. Pat. No. 6,261,519 does not
further draw the sample passed a test site to clear the test site
so that diffraction or non-diffraction at the test site can be
determined.
[0007] The methods, systems and devices discussed above do not
provide a means for directing a sample to a test surface and then
clearing the test surface of sample so that diffraction or
non-diffraction can be determined. Furthermore, the prior art fails
to provide a device in which a user of the device can control the
position of a sample with in the device. What is needed is a
simple, easy to use method, system and device for detecting an
analyte that provides a means for directing a sample to a test
surface and then clears the test surface of enough sample so that
diffraction, and binding, can be accurately determined and allows a
user of the device to control movement and incubation or reaction
time of a sample within the device.
SUMMARY OF THE INVENTION
[0008] The present invention provides diagnostic devices comprising
a means for inducing a pressure differential on a sample to direct
the sample to a test surface. In one embodiment, the means for
inducing a pressure differential on a sample to direct the sample
to a test surface comprises a syringe or a piston for pushing or
pulling a fluid sample to the test surface. In one embodiment, the
diagnostic device is a diffraction-based diagnostic device and the
means for inducing a pressure differential on a sample to direct
the sample to a test surface also further directs the sample past
the test surface and removes most of the sample from the test
surface so that the test surface can be observed by an individual
or read by an analyzer. In a desirable embodiment, the test surface
is located on a test strip that can be removed from the device and
observed by an individual or inserted into an analyzer.
[0009] Features, aspects and advantages of the present invention
will become better understood with reference to the following
description and the appended claims. The accompanying drawings,
which are incorporated in and constitute a part of this
specification, illustrate several examples of the invention and,
together with the description, serve to explain the principles of
this invention.
BRIEF DESCRIPTION OF THE FIGURES
[0010] The invention is hereinafter more particularly described by
way of examples with reference to the following drawings in
which:
[0011] FIG. 1 is a top view of a diagnostic device that includes a
pressure-assisted means for directing a sample to a test
surface.
[0012] FIG. 2 is a side view of the diagnostic device.
[0013] FIG. 3 is a cross-sectional view of the diagnostic device
taken through line 3-3 of FIG. 2.
[0014] FIG. 4 is a top view of a diagnostic test strip separated
from the device.
[0015] FIGS. 5, 6 and 7 are cross-sectional views of the diagnostic
device taken through line 3-3 of FIG. 2 in various stages of
operation of the pressure-assisted means.
[0016] FIG. 8 is a top view of the diagnostic device after
operating the pressure-assisted means.
[0017] FIG. 9 is a top view of the diagnostic device illustrating
one mode of removal of a removable test strip.
[0018] FIG. 10 is a side view of the removed test strip.
[0019] Repeated use of reference characters in the present
application and drawings is intended to represent the same, similar
or analogous features or elements of the invention.
DETAILED DESCRIPTION
[0020] Although the present invention is described in the context
of several specific examples, configurations and embodiments, it
will be appreciated that further combinations or alterations of the
examples, configurations and embodiments illustrated herein and
described herein may be made by one skilled in the art without
departing from the spirit and scope of the present invention. In
addition, although reference is often made with respect to
diffraction-based diagnostic devices, methods and systems for
detecting a protein, those skilled in the art will appreciate that
other modifications may be made to adapt the diagnostic devices,
methods and systems for use with non-diffraction based diagnostic
devices, methods and systems and for detecting analytes other than
proteins. In the following discussion, reference is made to several
figures to illustrate a few specific examples and embodiments of
the present invention.
[0021] The present invention provides a diagnostic device that
comprises a means for inducing a pressure differential on a sample
to direct the sample to a test surface. The means for inducing a
pressure differential on a sample to direct the sample to a test
surface may direct all or a portion of the sample to the test
surface. In addition, the means for inducing a pressure
differential on a sample to direct the sample to a test surface
also further directs the sample past the test surface to remove
excess or unreacted sample from the test surface and may include
additional means or structures to do so. Desirably, the sample is
directed past the test surface after the sample or a portion of the
sample has become bound, reacted or otherwise interacted with the
test surface.
[0022] One embodiment of the present invention provides a device
and method for directing a sample to a diffraction-based test
surface and is described and illustrated herein. For example, a
diffraction-based diagnostic device can be used to direct a liquid
sample, such as blood, to a diffraction-based test surface that
tests for one or more analytes such as a protein, such as
C-reactive protein, IgE antibodies and so forth.
[0023] Examples of methods, systems and devices for detecting an
analyte via the formation of a diffraction image are disclosed and
described in U.S. Pat. No. 5,922,550, U.S. Pat. No. 6,020,047, U.S.
Pat. No. 6,221,579 and International Publication No. WO 98/27417
which are hereby incorporated by reference herein in their
entirety. The devices described in the above-referenced documents
can be produced by printing a species onto a surface. The species
is selected to bind, react or otherwise associate with an analyte
of interest and is referred to herein as a "binder". A binder may
include any chemical species, compound, composition, moiety,
particle and so forth that will bind, react or otherwise associate
with the analyte of interest. Preferably, the binder is specific to
the analyte of interest or a class of analytes of interest and does
not appreciably bind, react or otherwise associate with any other
matter that may be found in the sample of interest. The binder can
be any analyte-specific receptor material that can be printed onto
a substrate and that will specifically bind to an analyte of
interest.
[0024] Thus, the binder is one part of a specific binding pair with
the analyte; examples of analyte/binder pairs include, but are not
limited to: antigen/antibody, such as IgE antibody/anti-IgE
antibody; antibody/antibody-binding protein (e.g., Protein A or
Protein G); enzyme/substrate; oligonucleotide/DNA; chelator/metal;
enzyme/inhibitor; bacteria/receptor; bacteria/antibody to bacterial
cell markers; or bacteria/anti-CRP antibody; virus/receptor or
Influenza A and anti-Influenza A antibodies;
fungus/anti-Aspergillus antibody; cellular toxin/receptor; cellular
toxin/antibody to toxin; fungus/receptor; hormone/receptor;
DNA/RNA, or RNA/RNA; oligonucleotide/RNA; and binding of these
species to any other species, as well as the interaction of these
species with inorganic species. The binder material that is printed
onto the substrate is characterized by an ability to specifically
bind the analyte or analytes of interest. The variety of materials
that can be used as a binder material are limited only by the types
of material which will combine selectively (with respect to any
chosen sample) with the analyte. Sub-classes of materials which can
be included in the overall class of receptor materials includes
toxins, antibodies, antigens, hormone receptors, parasites, cells,
haptens, metabolites, allergens, nucleic acids, nuclear materials,
autoantibodies, blood proteins, cellular debris, enzymes, tissue
proteins, enzyme substrates, coenzymes, neuron transmitters,
viruses, viral particles, microorganisms, proteins, saccharides,
chelators, drugs, and any other member of a specific binding pair.
This list only incorporates some of the many different materials
that can be printed onto the substrate to produce a diagnostic
device. Whatever the selected analyte of interest is, the binder is
designed to bind, react or otherwise associate with the analyte(s)
of interest.
[0025] Generally, the binder is printed onto a substrate, for
example a plastic film, in a defined pattern such that the
binder-printed film does not diffract electromagnetic radiation
when the electromagnetic radiation is reflected off of or
transmitted through the binder-printed film but diffracts
electromagnetic radiation after the binder-printed film is exposed
to the analyte and the analyte has bound, reacted or otherwise
associated with the binder. Alternatively, the binder-printed film
or surface may exhibit a measurable increase or decrease in
diffraction after exposure to the analyte. For example, a film may
be printed with a binder such that the binder-printed film does not
diffract light but does diffract after an analyte binds, associates
or otherwise reacts with the binder-printed surface. In another
example, the binder-printed film initially diffracts light but does
not diffract light or diffracts less after an analyte binds,
associates or otherwise reacts with the binder-printed surface. In
yet another example, the film may be printed with a binder so that
binder-printed film initially diffracts light but when the analyte
binds with binder-printed surface, light is diffracted to a
measurably greater extent. Thus, the presence of analyte can be
determined by a measurable change in diffraction of light that is
transmitted through or reflected off of the substrate surface. If
light or other electromagnetic radiation is to be transmitted
through the surface of a film to detect diffraction, it is
desirable that the film is transparent or at least partially
transparent to the light or other electromagnetic radiation that
will be used to detect diffraction.
[0026] Devices of the present invention include a surface or at
least a portion of a surface that is printed with a binder. The
printing of the surface may be accomplished by microcontact
printing the binder onto the surface in a defined pattern.
Microcontact printing is desirable and allows printing of patterns
with size features of about 100 .mu.m and smaller. Features in this
size range are desirable for diffraction when the electromagnetic
radiation wavelength is in the spectrum of visible light, from
about 4000 Angstroms to 7000 Angstroms. However, it is noted that
light over other wavelengths, both longer and shorter wavelength
electromagnetic radiation, may be used to detect diffraction. A
pattern of binder allows for the controlled attachment of analyte
or analyte receptor. An elastomeric stamp may be used to transfer
binder to a surface. If the stamp is patterned, a patterned binder
layer will be printed on the surface when the stamp is wet with the
binder, dried, and then contacted with the surface.
[0027] Gold-coated, printed films that produce diffraction patterns
and methods of contact printing such films are described and
disclosed in U.S. Pat. No. 6,020,047 and U.S. Pat. No. 6,048,623,
which are hereby incorporated by reference herein in their
entirety. U.S. Pat. Nos. 6,020,047 and 6,048,623 describe methods
of microcontact printing self-assembling monolayers that allow for
the selective placement of reagents that can react chemically or
physically with an analyte or a group of analytes that are of
interest to produce a diffraction image.
[0028] Generally, an analyte may be any stimulus including but not
limited to any chemical or biological species, compound,
composition, moiety, particle, and so forth that that will bind,
react or otherwise associate with the binder or with which the
binder will respond. Analytes that are contemplated as being
detected include, but are not limited to, one or more the
following: species of bacteria, including, but not limited to,
Hemophilis, Neisseria meningitides serogroups A, B, C, Y and W135,
Streptococcus pneumoniae; yeasts; fungi; viruses including, but not
limited to, Haemophilus influenza type B or RSV; rheumatoid
factors; antibodies including, but not limited to, IgG, IgM, IgA
and IgE antibodies; antigens including, but not limited to,
streptococcus Group A antigen, streptococcus Group B antigen, viral
antigens, fungal antigens, an antigen derived from microorganisms,
antigens associated with autoimmune diseases, influenza and tumors;
allergens; enzymes; hormones; saccharides; proteins, such as
C-reactive protein (CRP); lipids; carbohydrates; drugs including,
but not limited to, drugs of abuse and therapeutic drugs, nucleic
acids; haptens, environmental agents, other blood-born disease
markers; and so forth.
[0029] A binder may be microprinted on a polymer film or other
substrate. Desirably, a binder is selected and printed that is an
analyte-specific receptor material and specifically binds to the
analyte or class of analytes of interest. Thus, the binder material
and analyte are defined as a specific binding pair with the
analyte; examples of analyte/binder pairs include, but are not
limited to, antigen/antibody, antibody/antibody-binding protein,
enzyme/substrate, oligonucleotide/DNA, chelator/metal,
enzyme/inhibitor, bacteria/receptor, virus/receptor, cellular
toxin/receptor, fungus/receptor, hormone/receptor, DNA/RNA, or
RNA/RNA, oligonucleotide/RNA, and binding of these species to any
other species, as well as the interaction of these species with
inorganic species. The binder material that is printed on to a
substrate layer is characterized by an ability to specifically bind
the analyte or analytes of interest. The variety of materials that
can be used as a binder material are limited only by the types of
material which will combine selectively (with respect to any chosen
sample) with the analyte.
[0030] Subclasses of materials which can be included in the overall
class of binder materials include toxins, antibodies, antigens,
hormone receptors, parasites, cells, haptens, metabolites,
allergens, nucleic acids, nuclear materials, autoantibodies, blood
proteins, cellular debris, enzymes, tissue proteins, enzyme
substrates, coenzymes, neuron transmitters, viruses, viral
particles, microorganisms, proteins, saccharides, chelators, drugs,
and any other member of a specific binding pair.
[0031] U.S. Pat. No. 6,180,288 and International Publication No. WO
98/43086 disclose and describe the use of one or more responsive
gels coated on a patterned self-assembling monolayer and the use of
such devices. The responsive gels described therein react or
respond to a stimulus, i.e. an analyte, to produce a diffraction
image. U.S. Pat. No. 6,180,288 and International Publication No. WO
98/43086 are both hereby incorporated by reference herein in their
entirety.
[0032] Diffraction-based detectors and methods of detection using
optical diffraction that do not require self-assembled monolayers
are disclosed and described in U.S. Pat. No. 6,060,256 and
International Publication No. WO 99/31486. U.S. Pat. No. 6,060,256
and International Publication No. WO 99/31486 are hereby
incorporated by reference herein in their entirety. U.S. Pat. No.
6,060,256 and International Publication No. WO 99/31486 also
disclose and describe the optional addition of nutrients for a
specific class of microorganisms with such diagnostic devices,
systems and methods to provide for the detection of lower
concentrations of analytes.
[0033] U.S. Pat. No. 6,221,579 and International Publication No. WO
00/34781 disclose and describe the addition of diffraction
enhancing elements. Diffraction enhancing element particles that
may be used with the present invention include, but are not limited
to, glass, cellulose, synthetic polymers or plastics, latex,
polystyrene, polycarbonate, bacterial or fungal cells, metallic
sols, and so forth. A desirable particle size ranges from a
diameter of approximately 0.05 .mu.m to 100.0 .mu.m. The
composition of the element particle and structural and spatial
configuration of the particle is not critical to the present
invention. However, it is desirable that the difference in
refractive index between the medium and the enhancing element is
between 0.1 and 1.0. Diffraction enhancing elements are optionally
included in such devices, systems and methods to provide for the
detection of smaller species of analyte, such as proteins, DNA,
RNA, other low molecular weight analytes and low molecular weight
surface markers on organisms. U.S. Pat. No. 6,221,579 and
International Publication No. WO 00/34781 describe the modification
of microspheres so that the microspheres are capable of binding
with a target analyte and to the device surface. The microspheres
are capable of producing a substantial change in height and/or
refractive index to enhance diffraction, thereby increasing the
efficiency of such devices, systems and methods and can provide for
the detection of smaller species of analyte. U.S. Pat. No.
6,221,579 and International Publication No. WO 00/34781 are hereby
incorporated by reference herein in their entirety.
[0034] International Publication No. WO 00/36416 describes and
discloses devices and systems comprising a patterned deposition of
antibody-binding proteins for detecting antibodies. International
Publication No. WO 00/36416 is also hereby incorporated by
reference herein in its entirety.
[0035] FIG. 1 is a topside view of the exterior of device 100. In
the embodiment illustrated in FIGS. 1-10, the device 100 comprises
a housing 20 and a test strip 40. A top view of test strip 40 is
illustrated in FIG. 4. To provide a diffraction-based diagnostic
test and device, test strip 40 includes a test surface 42 on to
which a binder 44 is printed in a defined pattern (not
illustrated). Diffraction-based test methods and devices for
detecting one or more analytes are described in detail in the
above-referenced patents and patent applications. Persons of skill
in the art will recognize that other test strips and test methods
may be used with the present invention.
[0036] FIG. 2, is left side view of device 100. FIG. 3, is a
cross-sectional view of device 100 taken through line 3-3 of FIG.
2. In this illustrated embodiment, the device 100 is sealingly
attached to a removable test strip 40 to form a chamber 30 into
which a sample can be directed so that sample may contact test
strip 40 and test surface 42. The housing 100 further comprises an
opening 22 for receiving a sample and a channel 24 connecting the
opening 22 to chamber 30 so that sample may be directed from
opening 22 to chamber 30. In another embodiment, the opening 22 may
further comprise a collection pad onto which a sample may be placed
or otherwise deposited for testing. For example, an individual may
contact a freshly lanced finger or other body part to the
collection pad to deposit a blood sample for testing within the
device 100. The collection pad and opening 22 are in fluid
communication and connected to chamber 30 via channel 24. The
sample can be directed from the opening 22 to test surface 44 by
operating the means for inducing a pressure differential on a
sample to direct the sample to a test surface. The means for
inducing a pressure differential on a sample to direct the sample
to a test surface may be any means that can be used to direct,
force, urge or otherwise compel a sample from one location to
another location.
[0037] In the embodiments illustrated in FIGS. 1-10, the means for
inducing a pressure differential on a sample to direct the sample
to a test surface is a syringe or a syringe-like device,
illustrated generally as 50. Exemplary means for inducing a
pressure differential on a sample to direct the sample to a test
surface include any device for imparting pneumatic, hydraulic or
mechanical pressure on a sample, such as, a syringe, a piston, a
pump, a bladder, a vacuum and so forth. The syringe-like device 50
illustrated comprises a piston 52 that is slidingly and sealingly
engaged with the inner wall of a cylindrical chamber 56. The
syringe-like device 50 is operated by either depressing or pulling
on handle 54 that is connected to piston 52 to induce a positive or
negative pressure differential and push or pull a sample,
respectively. In this illustrated embodiment, the means for
inducing a pressure differential on a sample to direct the sample
to a test surface, the syringe-like device 50, is adapted and
arranged to induce a negative pressure differential on a sample and
pull the sample through the device 100 as the handle 54 is
extended. In at least one particular embodiment, the inner wall of
a cylindrical chamber 56 is provided with ridges 58, detents or
other means of informing a user of the device that a particular
position is reached and notifies the user to stop pulling on the
handle for a short period of time so that the device or contents of
the device can perform a particular function, such as diluting or
filtering or lysing the sample.
[0038] The operation of a device of the present invention and a
method of performing a diffraction-based diagnostic test will now
be described with respect to detecting C-reactive protein (CRP), a
biomarker that indicates bacterial infection. Persons of skill in
the art will recognize that devices and methods of the present
invention can be adapted and modified to perform other types of
diagnostic tests, including diagnostic test that are not
diffraction based, such as pH tests, lateral flow tests, or color
strips, and to detect analytes other than CRP. FIGS. 5, 6 and 7 are
cross-sectional views of the diagnostic device taken through line
3-3 of FIG. 2 in various stages of operation of the
pressure-assisted means. The position of a liquid sample within the
device in the various stages is illustrated by dashed lines.
[0039] A health-care professional or a non-professional may use the
following described version of the illustrated device to detect CRP
in blood and determine if a person from whom a blood sample, or
possibly another type of sample, is obtained is suffering from a
bacterial infection. With the handle 54 in the unextended position
illustrated in FIG. 1, a volume of blood, for example a drop of
blood, is contacted to the collection pad and opening 22. Once the
sample has contacted the collection pad, handle 54 may be extended
to Position 1 as illustrated in FIG. 5. The volume of blood is then
drawn from the collection pad, through opening 22 and into channel
24 by the vacuum created when handle 54 is moved from a closed
position to Position 1. In FIG. 5, the sample 60 is illustrated
entering optional chamber 34. Optional chambers may be included to
provide for various functions. For example, chamber 34 may be
provided in the device to include a filter for removing one or more
undesirable components from a sample, a diluent to lower the
viscosity of and thus increase the flow of a sample through the
device, or to contain a reactant, an additive or other useful
composition. In a desired embodiment, the diagnostic device
includes a means for diluting a sample, for example a diluent, in
chamber 34. In this desired embodiment, chamber 34 may contain a
diluent or any other composition that may be used to dilute,
dissolve or otherwise react with one or more components in a sample
or to perform another desirable function on a sample so that the
sample is affected in some manner that provides more reliable test
results for the analyte being tested. Sample contacts the means for
diluting a sample 34 via channel 24 when handle 54 is extended to
Position 1.
[0040] The device may be further provided with yet another optional
chamber 36. Chamber 36 may be provided in the device to include a
filter for removing one or more undesirable components from a
sample, a diluent to lower the viscosity of and thus increase the
flow of a sample through the device, or to contain a reactant, an
additive or other useful composition. In a further desirable
embodiment, the diagnostic device includes a means for separating
one or more components from a sample in chamber 36. Examples of
means for separating one or more components from a sample include a
membrane, filter media, porous films, nonwoven films, paper, etc.
Such means for separating one or more components from a sample may
be used to remove one or more components from a sample that are
undesirable or that may adversely affect testing. For example, it
may be desirable to remove red blood cells from a blood sample via
filtration, lysing or agglutination. Removal of red blood cells
from a sample may improve the function of diagnostic devices and
methods because red blood cells may interfere with the analyte
binding or otherwise associate with the printed binder; thus,
removal could improve test accuracy. The means for separating one
or more components from a sample may be general and remove a
component or components based on a particular property, for
example, size or molecular weight. Or, the means for separating one
or more components from a sample may be specific to a particular
component, for example a bilirubin-binding layer may be included to
remove bilirubin. Sample is further directed through channel 24 and
into chamber 36 by extending handle 54 to Position 2. Position 2 is
illustrated in FIG. 6. In Position 2, the sample is illustrated as
contacting the test surface 44. However, the number of positions
may vary and the location of the sample within the device may vary.
Once the sample has contacted the test surface 44, handle 54 can be
further extended, preferably fully extended, to remove excess
sample from the test surface so that the test surface can be read.
Advantageously, if the volume of chamber is greater than the volume
of blood that is produced from a freshly lanced finger
(approximately 25 .mu.L) or greater than the average volume (for
example greater than 50 .mu.L or even greater than 100 .mu.L)) the
liquid sample can be safely stored before the test strip 40 is
removed from the device 100. In a desirable embodiment, test strip
40 is removably attached to the device 10 and can be snapped off of
or otherwise removed from the device to be viewed or placed in an
analyzer for viewing or interpreting the results.
[0041] In another desirable embodiment, the device is provided with
windows and/or indicia, for example numbered windows 1, 2 and 3
illustrated in FIG. 8, to assist a user in operating the device.
After placing a sample on the touch pad 22, the user pulls handle
54 and aligns piston 52 with Position 1 to pull a sample from the
touch pad through channel 24 and into the means for diluting a
sample 34. Position 1 is illustrated in FIG. 5 and the sample is
illustrated as dashed area. The sample may then be allowed to
dilute, dissolve or otherwise react with a desired composition in
the chamber for a particular period of time. The device may contact
one or more compositions in chamber 34 that can be used to modify
the sample in some manner. For example, a composition may be
provided to reduce the viscosity of the sample, dissolve solids in
the sample, or add reactants or diffraction enhancing elements to
the sample. Next, the user further pulls handle 54 to align piston
52 with Position 2 to draw the sample further through channel 24,
through the means for separating 36 and into chamber 30. Position 2
is illustrated in FIG. 6. In this described embodiment, the sample
has been dissolved in a diluent and one or more desirable
components have been removed from the sample before the sample
contacts the binder-printed test surface 44. Next, the user further
pulls handle 24 to Position 3 to remove excess sample from the test
surface. Position 3 is illustrated in FIG. 7. The test strip 40 may
now be removed from the device 100 and observed or inserted into a
reader to be interpreted.
[0042] Although FIGS. 1-10 illustrate a syringe-like device 50 as a
means for inducing a pressure differential on a sample, one skilled
in the art could configure and construct a device that comprises a
means for inducing a pressure differential on a sample that is not
a syringe or a syringe-like device. Furthermore, one skilled in the
art will appreciate that the devices of the present invention may
be configured and constructed to comprise a means for inducing a
pressure differential on a sample that uses a positive pressure
differential instead of a negative pressure differential to push
rather than pull a sample to the test surface. Examples of means
for inducing a positive pressure differential include a pump, a
plunger, a piston as well as a syringe. The means for inducing a
pressure differential may be used to either pull a sample from an
opening 22 to a test surface 44 or to push a sample from an opening
22 to a test surface 44 as long as the means directs a sample or a
portion of a sample to the test surface so that the sample can be
analyzed.
[0043] While various patents and other reference materials have
been incorporated herein by reference, to the extent there is any
inconsistency between incorporated material and that of the written
specification, the written specification shall control. In
addition, while the invention has been described in detail with
respect to various specific examples, illustrations and embodiments
thereof, it will be apparent to those skilled in the art that
various alterations, modifications and other changes may be made to
the invention without departing from the spirit and scope of the
present invention. It is therefore intended that the appended
claims cover all such modifications, alterations and other
changes.
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