U.S. patent application number 11/930270 was filed with the patent office on 2008-03-06 for method and apparatus for point of care osmolarity testing.
Invention is credited to James N. Humenik, Govindarajan Natarajan, Scott D. Partington, Srinivasa S. N. Reddy.
Application Number | 20080053206 11/930270 |
Document ID | / |
Family ID | 37429214 |
Filed Date | 2008-03-06 |
United States Patent
Application |
20080053206 |
Kind Code |
A1 |
Natarajan; Govindarajan ; et
al. |
March 6, 2008 |
METHOD AND APPARATUS FOR POINT OF CARE OSMOLARITY TESTING
Abstract
An apparatus and a method are disclosed for providing point of
care testing for osmolarity of a bodily fluid. An apparatus is
disclosed as having a fluid pathway passing through it for
receiving and testing a sample fluid. The invention permits
osmolarity testing of a sample fluid wherein the sample fluid has a
volume of less than approximately 30 nL, and implements a method
and device to measure fluid osmolarity in a clinical setting
quickly and accurately, while also reducing evaporation of the
fluid.
Inventors: |
Natarajan; Govindarajan;
(Poughkeepsie, NY) ; Humenik; James N.;
(LaGrangeville, NY) ; Partington; Scott D.;
(Raleigh, NC) ; Reddy; Srinivasa S. N.;
(LaGrangeville, NY) |
Correspondence
Address: |
HOFFMAN, WARNICK & D'ALESSANDRO LLC
75 STATE ST
14TH FL
ALBANY
NY
12207
US
|
Family ID: |
37429214 |
Appl. No.: |
11/930270 |
Filed: |
October 31, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11163327 |
Oct 14, 2005 |
|
|
|
11930270 |
Oct 31, 2007 |
|
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Current U.S.
Class: |
73/64.47 ;
205/775; 324/71.1 |
Current CPC
Class: |
G01N 13/04 20130101;
Y10T 436/11 20150115 |
Class at
Publication: |
073/064.47 ;
205/775; 324/071.1 |
International
Class: |
G01N 13/04 20060101
G01N013/04; G01N 27/00 20060101 G01N027/00; G01N 27/26 20060101
G01N027/26 |
Claims
1. A method for determining osmolarity of a sample fluid,
comprising the steps of: communicating a sample fluid through a
conduit fixed to a base member directly to a sample receiving chip;
and determining osmolarity of the sample fluid.
2. The method of claim 1, wherein the sample receiving chip
includes: a substrate having a fluid pathway passing through the
substrate for receiving a sample fluid, the fluid pathway including
a first port, at least one second port, and a recessed channel, the
recessed channel enclosed in the substrate; and at least two
electrodes cosintered with multilayer ceramic positioned in the
substrate to contact the sample fluid in the recessed channel to
measure properties of the sample fluid.
3. The method of claim 1, wherein the step of communicating
includes applying an external pressure to a base unit, the base
unit including a chamber for receiving a first end of the conduit,
wherein the chamber includes a substantially flexible
partition.
4. The method of claim 1, wherein the step of determining the
osmolarity of the sample fluid includes measuring the conductivity
of the sample fluid to obtain a conductivity value and converting
the conductivity value to a corresponding osmolarity value.
5. The method of claim 1, wherein the communicating step includes
contacting an in vivo sample of bodily fluid on the human eye,
whereby the sample fluid is drawn into the conduit by capillary
force.
Description
BACKGROUND OF THE INVENTION
[0001] The current application is a divisional application of
co-pending U.S. patent application Ser. No. 11/163,327, filed on
Oct. 14, 2005, which is hereby incorporated by reference.
TECHNICAL FIELD
[0002] The present invention relates generally to the field of
devices for measuring the osmolarity of a relatively small volume
of fluid, and in particular to a method and an apparatus for
measuring, in vivo, the osmolarity of human tears.
RELATED ART
[0003] Dry eye syndrome (DES), a condition that occurs due to loss
of water from the tear film, is one of the most common complaints
seen by optometrists. Studies have found that DES is common in
about 15% of patients over the age of 50, with prevalence
increasing with age. Dry eye in general is caused by any condition
that increases tear film evaporation, or by any condition that
decreases tear production. For some patients, evaporation is
increased as a result of having larger eyes. Larger eyes cause
greater evaporation due to the larger surface area and the loss of
water. Tear production can also decrease from any condition that
decreases corneal sensation. Long-term contact lens wear, LASIK eye
surgery, trauma to the 5th nerve, and certain viral infections
cause decrease in corneal sensation. The treatment of DES depends
on the severity of the condition. Some patients find relief from
DES through the use of various artificial tears available on the
market. Additionally, some patients are prescribed Omega-3
containing supplements. There are cases where "punctual plugs" need
to be inserted to stop drainage of tears.
[0004] Osmolarity is the measure of the concentration of
osmotically active particles in a solution, which may be
quantitatively expressed in osmoles of solute per liter of
solution. It is known that when the tear film loses water, salt and
protein concentrations increase relative to the amount of water.
When the concentration of salt and protein increases relative to
the amount of water, osmolarity increases. Therefore, in order to
diagnose and treat DES patients, it is desirable for a treating
physician to quantify the osmolarity of a sample tear fluid. Some
current osmolarity measurement methods and devices available
include: osmotic pressure measurement, freezing point measurement,
and vapor pressure measurement.
[0005] In one approach, an osmometer is used to measure the osmotic
pressure exerted by a solution across a semi-permeable membrane. In
this approach, a solvent and solution are separated by the
semi-permeable membrane, which allows only solvent molecules to
pass through. The osmotic pressure of the solution can be
determined by measuring the excess pressure that must be applied to
the solution to prevent the solvent from passing into the
solution.
[0006] In another approach, the osmolarity of a sample fluid (e.g.,
a tear) can be determined by an ex vivo technique called "freezing
point depression." In this technique, solutes or ions in a solvent
(i.e., water) cause a lowering of the fluid freezing point from
what it would be without the ions. In the freezing point depression
analysis, the freezing point of the ionized sample fluid is found
by detecting the temperature at which a quantity of the sample
(typically on the order of about several milliliters) first begins
to freeze in a container (e.g., a tube). To measure the freezing
point, a volume of the sample fluid is collected into a container,
such as a tube. Next, a temperature probe is immersed in the sample
fluid, and the container is brought into contact with a freezing
bath or Peltier cooling device. The sample is continuously stirred
so as to achieve a supercooled liquid state below its freezing
point. Upon mechanical induction, the sample solidifies, rising to
its freezing point due to the thermodynamic heat of fusion.
Deviation of the sample freezing point from 0 degrees C. is
proportional to the solute level in the sample fluid (i.e.,
osmolarity value).
[0007] Another ex vivo technique for osmolarity testing measures
vapor pressure. In this method, a small, circular piece of filter
paper is lodged underneath a patient's eyelid until sufficient
fluid is absorbed. The filter paper disc is placed into a sealed
chamber, whereupon a cooled temperature sensor measures the
condensation of vapor on its surface. Eventually the temperature
sensor is raised to the dew point of the sample. The reduction in
dew point proportional to water is then converted into osmolarity.
However, because of induced reflex tearing, osmolarity readings are
not as accurate. Similarly, in vivo techniques, which attempt to
measure osmolarity by placing electrodes directly under the eyelid
of a patient, are likely to induce reflex tearing. As a result the
above-described approaches are neither convenient nor accurate for
an eye doctor operating in a clinical environment.
[0008] There is a need for a clinically feasible, nanoliter-scale
osmolarity measurement device, with the capability for reduced
evaporation, that does not suffer from the problems of the related
art.
SUMMARY OF THE INVENTION
[0009] An apparatus and a method are disclosed for providing point
of care testing for osmolarity of a bodily fluid. An apparatus is
disclosed as having a fluid pathway passing through it for
receiving and testing a sample fluid. The invention permits
osmolarity testing of a sample fluid wherein the sample fluid has a
volume of less than approximately 1 mL, with a preferred volume of
less than 30 nL, and implements a method and device to measure
fluid osmolarity in a clinical setting quickly and accurately,
while also reducing evaporation of the fluid.
[0010] A first aspect of the invention is directed to a sample
receiving chip comprising: a substrate having a fluid pathway
passing through the substrate for receiving a sample fluid, the
fluid pathway including a first port, at least one second port, and
a recessed channel, the recessed channel enclosed in the substrate;
and at least two electrodes positioned in the substrate to contact
the sample fluid in the recessed channel to measure properties of
the sample fluid.
[0011] A second aspect of the invention is directed to a device for
osmolarity testing, comprising: a base member; a sample receiving
chip fixed to the base member for receiving a sample fluid; and a
conduit fixed to the base member for depositing the sample fluid on
the sample receiving chip, the conduit including a first end and a
second end.
[0012] A third aspect of the invention is directed to a method for
determining osmolarity of a sample fluid, comprising the steps of:
communicating a sample fluid through a conduit fixed to a base
member directly to a sample receiving chip; and determining
osmolarity of the sample fluid.
[0013] The foregoing and other features of the invention will be
apparent from the following more particular description of the
embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The embodiments of this invention will be described in
detail, with reference to the following figures, wherein the like
designations denote like elements, and wherein:
[0015] FIGS. 1A-B show a cross sectional view of a sample receiving
chip according to one embodiment of the invention.
[0016] FIGS. 2A-B show a plan view of two embodiments of a first
substrate layer of the sample receiving chip of FIG. 1.
[0017] FIG. 3 shows a plan view of a second substrate layer of the
sample receiving chip of FIG. 1.
[0018] FIG. 4 shows a plan view of a third substrate layer of the
sample receiving chip of FIG. 1.
[0019] FIG. 5 shows a cross sectional view of the electrode windows
which provide access to electrodes for osmolarity testing.
[0020] FIGS. 6A-B show a cross sectional view of the electrode
contacts positioned on different surfaces the sample receiving chip
of FIG. 1.
[0021] FIG. 7 shows a plan view an osmolarity testing device to
collect a sample fluid and to test osmolarity of the sample
fluid.
[0022] FIG. 8 shows a plan view of an osmolarity testing device to
collect a sample fluid and to test osmolarity of the sample
fluid.
[0023] FIG. 9 shows a plan view of an osmolarity testing device to
collect a sample fluid and to test osmolarity of the sample
fluid.
DETAILED DESCRIPTION
[0024] Exemplary embodiments are described below for measuring the
osmolarity of a sample fluid. The embodiments are configured to
provide quick and accurate testing of a relatively small amount of
fluid.
[0025] Referring to FIGS. 1-4, a sample receiving chip for testing
osmolarity of a sample fluid according to one embodiment of the
invention is shown. It can be appreciated, that even though three
substrate layers are shown in the present embodiment, any number of
substrate layers can be used. Furthermore, while sample receiving
chip 2 is initially discussed in isolation, during operation sample
receiving chip 2 may be coupled to a device, as will be described
further below, including a base member; sample receiving chip 2
fixed to the base member for receiving a sample fluid; and a
conduit fixed to the base member for depositing the sample fluid on
sample receiving chip 2. Coupling receiving chip 2 to a device
allows for more convenient and effective point-of-care testing.
[0026] When the various substrate layers shown in FIGS. 1-4 are
combined, sample receiving chip 2 comprises: substrate 4 having
fluid pathway 6 passing through substrate 4 for receiving a sample
fluid. Fluid pathway 6 may include a first port 8, at least one
second port 10 (hereinafter simply "second port 10"), and a
recessed channel 12. As shown in FIG. 1, recessed channel 12 is
enclosed in substrate 4. Sample receiving chip 2 also includes at
least two electrodes 14 positioned in substrate 4 to contact the
sample fluid in the recessed channel to measure properties of the
sample fluid. Electrode windows 18, which are shown in FIGS. 2A, 3,
5, 7, and 8, are not shown in FIG. 1 for clarity. However, it
should be noted that substrate 4 may include electrode windows
8.
[0027] Referring to FIGS. 2A-B, a plan view of first substrate
layer 16 is shown. First substrate layer 16 forms an upper layer of
chip 2, as shown in FIG. 1. As shown in FIG. 2A, first port 8,
second port 10, and electrode windows 18 are openings formed in
first substrate layer 16 by, for example, mechanically punching-out
portions of first substrate layer 16. It can be appreciated,
however, that any technique for creating openings in a substrate
layer can be used. As will be described in further detail below, at
least two electrode windows 18 provide access to at least two
electrodes 14. In an alternative embodiment, shown in FIG. 2B,
first substrate layer 16 may include first port 8, and second port
10, but no electrode windows. As will be described in further
detail below, when substrate 4 does not include electrode windows
18, substrate 4 includes at least two electrodes (not shown)
connected to contacts 20 positioned on an external surface of
substrate 4. Although contacts 20 are shown in FIG. 2B as circular
in shape, it can be appreciated that contacts 20 can be any
suitable geometric shape.
[0028] Referring to FIG. 3, a plan view of second substrate layer
22 is shown. Second substrate layer 22 constitutes a middle layer
of chip 2, as shown in FIG. 1. In this embodiment, second substrate
layer 22 includes openings for first port 8, second port 10, and
recessed channel 12. Additionally, second substrate layer 22 may
include openings for electrode windows 18. First port 8, second
port 10, and recessed channel 12 are formed, by example, by
mechanically punching out the desired portion of second substrate
layer 22. In a preferred embodiment, second substrate layer 22 is
positioned below first substrate layer 16.
[0029] FIG. 4 shows a plan view of third substrate layer 24. Third
substrate layer 24 constitutes a bottom layer of chip 2, as shown
in FIG. 1. Third substrate layer 24 comprises at least two
electrodes 14 in the recessed channel to contact the sample fluid
and contacts 20 to connect to testing circuit 50 to measure
properties of the sample fluid. In a preferred embodiment, third
substrate layer 24 is positioned below first substrate layer 16 and
second substrate layer 22, respectively. Electrodes 14 are
positioned under recessed channel 12 to make contact with the
sample fluid, as shown in FIG. 3, and are preferably cosintered
with multilayer ceramic.
[0030] Due to traditional manufacturing methods for ceramic
substrates, traditional metal electrodes begin to deteriorate under
the higher temperatures necessary to bond and cure the substrate.
Ceramic particles and metal particles coalesce at different
temperature ranges and rates during sintering. Therefore,
reasonably matching metals and ceramics with similar densification
rates helps to obtain controlled part dimensions (outer and feature
dimensions), and defect free (cracks/breakage, etc) devices. In the
present invention, a cordierite based glass ceramic is preferred as
the base device material and a copper+nickel+glass ceramic is
preferred as the conductor material. The nickel and copper
combination helps to avoid corrosion during use and storage of the
chip, as chemical reactions, such as corrosion, negatively
interfere with measurement. Additionally, the maximum sinter
temperature in a preferred embodiment is less than approximately
1000 degrees C.
[0031] Referring again to FIGS. 1-4, operation of a sample
receiving chip 2 will now be described in greater detail. During
operation, a relatively small amount of sample fluid is deposited
into first port 8. In a preferred embodiment, reliable osmolarity
measurement is obtained with a fluid sample volume of less than
approximately 30 nL. The sample fluid passes through first port 8
and recessed channel 12 formed in substrate layers 16 and 22,
respectively. First port 8 narrows as the sample liquid passes
through first substrate layer 16, and second substrate layer 22.
The fluid is drawn through first port 8 and recessed channel 12 by
venting second port 10. It can be appreciated that first port 8 and
second port 10 of sample receiving chip 2 may be a variety of
geometric configurations, so long as first port 8 funnels the
sample fluid into recessed channel 12 and second port 10 vents
recessed channel 12. However, the geometries of first port 8,
recessed channel 12, and second port 10, can influence fluid flow.
Second port 10 can be designed to control the rate at which the
sample fluid flows through recessed channel 12. As shown by FIG.
1B, additional second port 10 (or any number of additional second
ports) can be added to further influence fluid flow through
recessed channel 12. In a preferred embodiment, once the sample
liquid is drawn through recessed channel 12 by capillary action,
second port 10 becomes partially filled with the sample fluid, the
sample fluid being held by surface tension. Furthermore, a
hydrophilic substrate surface is preferably used to promote fluid
flow through recessed channel 12. This combination of surface
chemistry, channel geometry, and vent geometry is used to control
flow uniformity, rate, and residence time
[0032] Referring now to FIG. 5, a cross sectional view of one
embodiment of substrate 4, including electrode windows 18, is
shown. In this embodiment, recessed channel 12, containing the
sample fluid, flows in a direction perpendicular to electrodes 14.
It can be appreciated however, that different electrode
configurations can be used, as long as the sample fluid comes into
contact with the electrodes. Also shown in FIG. 5, at least two
electrode windows 18 provide access to at least two electrodes 14.
An external measurement device (not shown) can be inserted into the
openings formed by electrode windows 18 to contact electrodes 14,
via contacts 20. As a result, the conductivity of the sample fluid
may be determined. In alternative embodiments, as shown in FIGS.
6A-B, at least two electrodes 14 are connected to contacts 20 that
extend to and are positioned on an external surface of substrate 4.
As shown by comparing FIGS. 6A-B, contacts 20 may be positioned on
various external surfaces of substrate 4, so long as electrodes 14
come into contact with the sample fluid flowing through recessed
channel 12.
[0033] Referring now to FIG. 7, a point of care osmolarity testing
device 26 is shown. In one embodiment, device 26 for testing
osmolarity comprises: base member 28; sample receiving chip 2 fixed
to base member 28 for receiving a sample fluid; and conduit 30
fixed to base member 28 for depositing the sample fluid on sample
receiving chip 2. Conduit 30 includes first end 31 and second end
33. It should be noted, that sample receiving chip 2 may be
substantially identical to that described above, except for any
required mounting structure. In one embodiment, osmolarity testing
device 26, as shown in FIG. 7, further includes capillary
receptacle 32 including: base unit 34, including fastener 36 for
fixing conduit 30 to base unit 34, and chamber 38 for receiving
first end 31 of conduit 30. Conduit 30, containing the sample
fluid, may be fastened to capillary receptacle 32. Chamber 38
includes substantially flexible partition 40. Device 26 also
includes external pressure applying mechanism 42 to apply an
external pressure to substantially flexible partition 40 for
altering chamber pressure to discharge the sample fluid from second
end 33 of conduit 30. Mechanism 42 may include structure, for
example, to pump air, to provide a piezoelectric change that causes
flexible partition 40 to expand and contract in a controlled
manner, or any other now known or later developed structure to
apply a force to substantially flexible partition 40.
[0034] Referring again to FIG. 7, a preferred method for
determining osmolarity of a sample fluid will be described in
greater detail. In one embodiment, a method for determining
osmolarity of a sample fluid comprises the steps of: communicating
a sample fluid through conduit 30 fixed to base member 28; and
determining osmolarity of the sample fluid. Communicating a sample
fluid through conduit 30 may include contacting an in vivo sample
of bodily fluid on the human eye, whereby the sample fluid is drawn
into conduit 30 by capillary force. Typically, a treating physician
opens the lower eyelid of a patient and touches the tear in the
tear cavity with conduit 30. The tear is drawn into conduit 30 by
capillary force and held by surface tension. After the sample fluid
is collected by conduit 30, conduit 30 is placed in capillary
receptacle 32. The receptacle contains fastener 36 to isolate first
end 31 of conduit 30 extending into chamber 38. In the present
embodiment, the step of communicating also includes applying
external pressure 42 to base unit 34, base unit 34 including
chamber 38 for receiving first end 31 of conduit 30, wherein
chamber 38 includes substantially flexible partition 40. A positive
external pressure 42, such as low-pressure air, is applied to
substantially flexible partition 40. Partition 40 transfers the
pressure to chamber 38 and forces the sample fluid out as a drop
from second end 33 of conduit 30.
[0035] Next, the osmolarity of the sample fluid is determined by a
testing circuit 50. The osmolarity of the sample fluid can be
measured by sensing the energy transfer properties of the sample
fluid. The energy transfer properties can include, for example,
electrical conductivity, such that the impedance of the sample
fluid is measured, given a particular current that is transferred
into the sample fluid. Testing circuit 50 applies a current source
across the electrodes of sample receiving chip 2. Osmolarity of the
sample fluid may be determined by measuring the conductivity of the
sample fluid using conductivity measuring device 52 to obtain a
conductivity value and converting the conductivity value to a
corresponding osmolarity value using conversion system 54 (e.g., by
a calibration knowledge base). In this case, testing circuit 50
includes an electrical conductivity measurement circuit 56 to
determine osmolarity of the sample fluid. For example, measurement
circuitry 56 may provide electrical energy in a specified waveform
(such as from a function generator) to the at least two electrodes
bridged by the sample fluid. Furthermore, as shown in FIG. 7, base
member 28 may include a device for communicating results to a user,
e.g., a display device 142 for displaying a visual representation
of the osmolarity value. Alternatively, the osmolarity results can
be communicated and displayed at a remote location in any known
fashion.
[0036] In another embodiment, shown in FIG. 8, a treating physician
may pre-position a conduit 130 to a base member 128 of an
osmolarity testing device 126. Device 126 is similar to device 26
(FIG. 7) except Conduit 130 is fixed to base member 128 for
depositing the sample fluid on sample receiving chip 102. A tear is
then collected from the patient and is drawn into conduit 130 by
capillary force. First end 131 of conduit 130 extracts the sample
fluid, and second end 133 of conduit 130 deposits the sample fluid
on sample receiving chip 102. Therefore, the method for determining
osmolarity of a sample fluid, comprises: communicating a sample
fluid through conduit 130 fixed to base member 128 directly to
sample receiving chip 102; and determining osmolarity of the sample
fluid. Furthermore, osmolarity testing device 133 may include
hinged-cover 144 to protect conduit 130 and to make handling of
device 126 more convenient. In another embodiment, as shown in FIG.
9, conduit 130 may be fastened to hinged-cover 44. It should be
noted, that osmolarity testing device 126 can be a hand-held
device, allowing for convenient and effective point-of-care
treatment.
[0037] While this invention has been described in conjunction with
the specific embodiments outlined above, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, the embodiments of the
invention as set forth above are intended to be illustrative, not
limiting. Various changes may be made without departing from the
spirit and scope of the invention as defined in the following
claims.
* * * * *