Note: Descriptions are shown in the official language in which they were submitted.
CA 02566824 2006-11-21
"IMPROVED ELECTROCHEMICAL CELL"
Technical Field
This invention relates to disposable electrochemical sensors of the type used
for
s quantitative analysis, for example, of glucose levels in blood, or the like.
Background Art
Light transmissive electrodes are known in the prior art, however they have
not
previously been applied to amperometric cells. For example, GB 2 194 112
discloses the
use of optically transparent electrodes used to drive a microelectrophoresis
cell while laser
~o doppler velocimetry is used to determine the velocity and micro current
motion of charged
particles within the sample.
JP, A 05080018 discloses another approach to making transparent electrodes by
the
use of conductive glass for electrochromic and field emission devices.
JP, A 06310746 also teaches the use and formation of yet another type of
~ s conducting transparent electrode formed from the deposition of organic
conducting
polymers onto a glass slide. This type of electrode is useful in solar energy
collection cells.
Ullery, in US 4,254,546 also discloses a photovoltaic cell in which the top
layer is a light
collecting electrode.
US 4,782,265 discloses two spaced apart translucent electrodes useful in
luminescent
?o cells. However, US 4,782,265 specifically teaches that gold, silver,
aluminium, platinum
and the like are only suitable for the production of non-transmissive
electrodes.
In co-pending published applications W095/28634, W09700441,
W097/18465 and W097/18464 there are described various very thin
electrochemical
sensors or cells. These cells are by a pair
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of oppositely facing spaced apart electrodes which are formed as thin metal
coatings (for
example sputter coatings) deposited on thin inert plastic film (for example
100 micron
thick PET). The electrodes are separated one from the other by a spacer of
thickness of for
example 500 pm or less.
Such cells may be provided with one or more fluid passageways into and out of
the
sample reservoir whereby the cell may be filled with an analyte and air
expelled during
filling. In some embodiments the analyte is drawn into the cell by the energy
liberated as a
reagent contained therein dissolves.
The sensors are, as discussed above, very small and normally contain only
small
t o amounts of the liquid sample. Accurate measurement requires that the cell
be filled with
liquid. Even minute variations in the quantity of liquid in the cell can
effect the sensing
measurements. It can be difficult for a user to be sure that in use the cell
has been
uniformly filled with a sample to be analysed.
Further, sensors of the kind under discussion are usually intended to be
discarded
is after use. If a user is distracted after use or prior to disposal it is not
always easy for the
user to know which sensors have been used and which have not.
It is an object of the present invention to overcome or ameliorate at least
one of the
disadvantages of the prior art, or to provide a useful alternative.
Disclosure of the Invention
2o According to one aspect the present invention provides an amperometric
electrochemical cell comprising a first insulating substrate carrying a first
electrode, a
second insulating substrate carrying a second electrode, said electrodes being
disposed to
face each other and spaced apart by less than 500 Nm, and defining a sample
reservoir
therebetween, wherein at least one of said insulating substrates and the
electrode carried
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thereon includes an electromagnetic radiation transmissive portion in
registration with said
reservoir.
Preferably, both said insulating substrates and the electrodes thereon include
a
transmissive portion. Most preferably, the transmissive portion is formed by a
conductive
s metallic coating on the substrate, which is of a thickness such that it is
transparent or
tzanslucent. Suitable substances for the metallic coating include gold, indium
oxide, tin
oxide or mixtures thereof. A suitable substrate is PET.
According to a second aspect, the invention provides a method of filling an
amperometric cell comprising the steps of:
a) drawing a liquid sample into said cell comprising a first insulating
substrate carrying a
first electrode, a second insulating substrate carrying a second electrode,
said electrodes
being disposed to face each other and spaced apart by less than 500 pro, and
defining a
sample reservoir therebetween, wherein at least one of said insulating
substrates and the
electrode carried thereon includes an electromagnetic radiation transmissive
portion in
I 5 registration with said reservoir
b) exposing the transmissive portion to electromagnetic radiation
c) monitoring a property of the electromagnetic radiation passing and/or
reflected through
said transmissive portion
d) comparing said monitored property with a predetermined value indicative of
the cell
2o being filled, and
e) continuing to draw the liquid sample into the cell until said monitored
property reaches
said predetermined value.
According to a third aspect, the invention provides a method of determining
whether
an amperometric cell is filled with a liquid sample, said cell comprising a
first insulating
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substrate carrying a first electrode, a second insulating substrate carrying a
second
electrode, said electrodes being disposed to face each other and spaced apart
by less than
500 p.m, and defining a sample reservoir therebetween, wherein at least one of
said
insulating substrates and the electrode carried thereon includes an
electromagnetic
radiation transmissive portion in registration with said reservoir, said
method comprising
the steps of:
a) exposing said transmissive portion to electromagnetic radiation,
b) monitoring a property of the electromagnetic radiation passing and/or
reflected through
said transmissive portion, and
1 o c) comparing said monitored property with a predetermined value indicative
of the cell
being filled.
Suitable forms of electromagnetic radiation include visible, ultraviolet,
infra-red and
laser light. Daylight is especially preferred. The monitored property can
include optical
density, wavelength, refractive index and optical rotation.
t 5 In preferred embodiments, it is envisaged that the sample will be blood.
The
electromagnetic property may be monitored inside (for instance with a fibre
optical device)
or outside the cell, and the electromagnetic radiation may pass substantially
directly
through the cell or be internally reflected within the cell.
According to a fourth aspect, the invention consist in a method for monitoring
an
2o analyte in a liquid sample comprising the steps of
a) drawing the sample into an amperometric electrochemical cell comprising a
first
insulating substrate carrying a first electrode, a second insulating substrate
carrying a
second electrode, said electrodes being disposed to face each other and spaced
apart by less
than 500 Vim, and defining a sample reservoir therebetween, wherein at least
one of said
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insulating substrates and the electrode carried thereon includes an
electromagnetic
radiation transmissive portion in registration with said reservoir,
b) exposing the transmissive portion to electromagnetic radiation
c) monitoring a property of the electromagnetic radiation passing andlor
reflected
through said transmissive portion
d) comparing said monitored property with a predetermined value indicative of
the
cell being filled, and
e) prior to, simultaneously with or after any one of steps b) to d) applying a
potential across the electrochemical cell and measuring the resultant current
to detect the
to analyte.
The method of the above aspect may also further comprise the step of:
f) repeating steps a) to e) until the monitored property reaches the
predetermined
value.
In one preferred embodiment, the method is repeated on different cells, with
blood as
~ 5 the sample and visible light the electromagnetic radiation, until a valid
measurement is
obtained for blood glucose.
In a fifth aspect, the invention provides an apparatus for determining whether
an
amperometric cell according to the first aspect is filled with a liquid
sample, said apparatus
comprising an electromagnetic radiation means adapted to expose said
transmissive portion
20 of said cell to electromagnetic radiation,
a monitoring means adapted to monitor a property of the electromagnetic
radiation passing
andlor reflected through said transmissive portion, and
a means for determining whether said monitored property has reached a
predetermined
value indicative of the cell being filled.
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Preferably, said apparatus may also include means to apply potential across
the
amperometric cell and detect the resultant current. It may also include a
validation means
to confirm the cell is filled with a liquid sample.
"Comprising" as herein used is used in an inclusive sense, that is to say in
the sense
of "including" or "containing". The term is not intended in an exclusive sense
("consisting" of or "composed of').
Light-transmissive cells intended for spectrophotometric use are well known.
However this has not previously been accomplished in a cell wherein the only
surfaces
suitable for a window are entirely covered by a metal electrode. One skilled
in the art will
~o appreciate that whilst the embodiments of the invention are described with
respect to light
transmissive conductive coatings, such coatings may be also be transparent to
some other
forms of electromagnetic radiation which are not visible to the human eye.
Best Mode for Carrying out the Invention
The invention will now be particularly described by way of example only
reference
t 5 to the accompanying schematic drawings wherein:
Figure 1 shows a cross section of a wall of a cell according to the present
invention.
Figure 2 shows a cell according to one embodiment of the present invention.
Figure 3 shows a cross section of the cell in Figure 2.
An embodiment of the invention will now be described by way of example only.
2o Referring firstly to figure l, each wall of the cell 2,12 comprises an
insulating substrate
1,11 carrying an electrode 3,13 thereon.
The embodiment is generally in accordance with the apparatus described in our
co-
pending published application W097/18464. The apparatus hereof corresponds
substantially to the apparatus described in that application
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with the difference that electrode layer 3,13 which in published application
W09~/18464 was
sputter coated palladium having a thickness of 100-1000 Angstrom, is replaced
according
to the present invention, by a light-transmissive conductive metallic coating
of a thickness
such that it is transparent or translucent. Gold, indium oxide, tin oxide and
mixtures of
s indium and tin oxides or other suitable light-transmissive conductive
metallic coating may
be utilised. Those skilled in the art will appreciate that transparent
inorganic and organic
polymers or mixtures thereof could also be used. Substrate 1 is also light-
transmissive.
In one embodiment, the cell takes the form as shown in Figures 2 or 3. The
cell
comprises a first insulating substrate 1 consisting of a Melinex~' PET layer,
a first electrode
0 3 consisting of a conductive metallic layer on substrate 1, an adhesive
layer 7, a PET
spacer 9. a second adhesive layer 8, a second electrode 13 formed as a
metallic layer
formed as a metallic coating on second insulating substrate 11. Spacer 9
defines a sample
reservoir 4 having a thickness con esponding to the thickness of the spacer 9
together with
the thickness of adhesive Layers ? and 8. Access to the sample reservoir 4 is
provided at
~ 5 the side edge of the cell by notches 6.
At least one of the said insulating substrates and the electrode carried
thereon
includes an electromagnetic radiation transmissive portion 20 in registration
with the
reservoir 4,
In preferred embodiments of the invention, a sample to be analysed is
introduced
2o to the cell by capillary action. The sample is placed on contact with notch
6 and is
spontaneously drawn by capillary action into the reservoir 4, displaced air
from the
reservoir 4 venting from the opposite notch 6. A surfactant may be included in
the
capillary space to assist in drawing in the sample.
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The cell is provided with connection means for example edge connectors whereby
the cell may be placed into a measuring circuit. In a preferred embodiment
this is achieved
by making spacer 9 shorter than cell walls 2, 12 and by making one wall 2 of
shorter length
than the other 12. This forms a socket region having contact areas
electrically connected
s with the working and counter electrodes of a sensing apparatus. A simple
tongue plug
having corresponding engaging conduct surfaces can then be used for electrical
connection.
Connectors of other form rnay be devised.
Chemicals for use in the cell may be supported on the cell electrodes or
walls,
may be supported on an independent support contained within the cell or may be
self
t o supporting.
In use, when the cell is filled with the liquid sample, e.g. blood, a film of
the
sample covers the inside of the transmissive portion 20 formed by substrate
1,11 and metal
electrode 3,13 over reservoir ~, thereby indicating to the user when the cell
is adequatety
filled, and clearly differentiating a used sensor from an unused one.
~ 5 Apart from simple visual inspection, a user can also monitor the filling
of the cell by
exposing the electromagnetic radiation transmissive portion 20 to
electromagnetic radiation
such as infra-red, ultraviolet light or laser light and monitoring a property
of the
electromagnetic radiation (for example, optical density, colour or optical
rotation) as it
exits the cell, either by another transmissive portion on the opposite side of
the reservoir, or
2o as a result of internal reflection within the reservoir.
A particular embodiment of an apparatus suitable for carrying out the
inventive
method is hereby described. The apparatus has means for holding and orienting
a cell
according to the present invention and exposing the electromagnetic portion of
the cell to
allow an electromagnetic radiation source, e.g. a light beam, to enter the
reservoir.
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Optionally, the apparatus may also be equipped with means for automatically
placing
the cells into the said holding means.
The path of the light beam is substantially linear, and it exits the cell
either via
another transparent portion of the cell, or is reflected back through the
first mentioned
s transmissive portion. The electromagnetic radiation leaving the cell is
monitored by an
appropriate detector. This detector monitors a property of the electromagnetic
radiation
leaving the cell for comparison with a predetermined value which is indicative
of the cell
being filled, for example if the cell is filled with blood up to or above the
transmissive
portion, a reduction in optical density will be detected. If the cell is empty
or only partially
~o filled to this point, the optical density will remain high but will reduce
as the reservoir is
filled until it reaches the predetermined value indicating a full cell. It
will be appreciated
that the apparatus could be made to continue filling until the cell was
satisfactorily filled,
by means of a feedback system. The apparatus could also be adapted so that it
performed
the necessary electrochemical measurements on the cell, thus reducing the need
for
~ 5 excessive sample movement.
The apparatus preferably also includes a validation means which is triggered
when it
is determined that the cell is full and the sensing measurement can be
accepted as valid.
As will be apparent to those skilled in the ari from the teaching hereof the
invention
may be embodied in other forms without departing herefrom.
