Note: Descriptions are shown in the official language in which they were submitted.
CA 02570186 2009-11-04
=
SYSTEM AND METHOD FOR QUALITY ASSURANCE OF A
BIOSENSOR TEST STRIP
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an apparatus for use in measuring signals
such
as those related to concentrations of an analyte (such as blood glucose) in a
biological fluid as well as those related to interferants (such as hematocrit
and
temperature in the case of blood glucose) to analyte concentration signals.
The
invention relates more particularly to a system and method for quality
assurance
of a biosensor test strip.
BACKGROUND OF THE INVENTION
Measuring the concentration of substances in biological fluids is an important
tool for the diagnosis and treatment of many medical conditions. For example,
the measurement of glucose in body fluids, such as blood, is crucial to the
effective treatment of diabetes.
Diabetic therapy typically involves two types of insulin treatment: basal, and
meal-time. Basal insulin refers to continuous, e.g. time-released insulin,
often
taken before bed. Meal-time insulin treatment provides additional doses of
faster acting insulin to regulate fluctuations in blood glucose caused by a
variety
of factors, including the metabolization of sugars and carbohydrates. Proper
regulation of blood glucose fluctuations requires accurate measurement of the
concentration of glucose in the blood. Failure to do so can produce extreme
complications, including blindness and loss of circulation in the extremities,
which can ultimately deprive the diabetic of use of his or her fingers, hands,
feet, etc.
1
CA 02570186 2009-11-04
Multiple methods are known for determining the concentration of analytes in a
blood sample, such as, for example, glucose. Such methods typically fall into
one of two categories: optical methods and electrochemical methods. Optical
methods generally involve spectroscopy to observe the spectrum shift in the
fluid caused by concentration of the analyte, typically in conjunction with a
reagent that produces a known color when combined with the analyte.
Electrochemical methods generally rely upon the correlation between a current
(Amperometry), a potential (Potentiometry) or accumulated charge
(Coulometry) and the concentration of the analyte, typically in conjunction
with
a reagent that produces charge-carriers when combined with the analyte. See,
for example, U.S. Patent Nos. 4,233,029 to Columbus, 4,225,410 to Pace,
4,323,536 to Columbus, 4,008,448 to Muggli, 4,654,197 to Lilja et al.,
5,108,564 to Szuminsky et al., 5,120,420 to Nankai et al., 5,128,015 to
Szuminsky et at., 5,243,516 to White, 5,437,999 to Diebold et at., 5,288,636
to
Pollmann et at., 5,628,890 to Carter et at., 5,682,884 to Hill et al.,
5,727,548 to
Hill et at., 5,997,817 to Crismore et al., 6,004,441 to Fujiwara et at.,
4,919,770
to Priedel, et al., and 6,054,039 to Shieh. The biosensor for conducting the
tests
is typically a disposable test strip having a reagent thereon that chemically
reacts with the analyte of interest in the biological fluid. The test strip is
mated
to a nondisposable test meter such that the test meter can measure the
reaction
between the analyte and the reagent in order to determine and display the
concentration of the analyte to the user.
FIG. 1 schematically illustrates a typical prior art disposable biosensor test
strip,
indicated generally at 10 (see, for example, U.S. Patent Nos. 4,999,582 and
5,438,271). The test strip 10 is formed on a nonconductive substrate 12, onto
which are formed conductive areas 14,16. A chemical reagent 18 is applied
over the conductive areas 14,16 at one end of the test strip 10. The reagent
18
will react with the analyte of interest in the biological sample in a way that
can
2
CA 02570186 2009-11-04
be detected when a voltage potential is applied between the measurement
electrodes 14a and 16a.
The test strip 10 therefore has a reaction zone 20 containing the measurement
electrodes 14a,16a that comes into direct contact with a sample that contains
an
analyte for which the concentration in the sample is to be determined. In an
amperometric or coulometric electrochemical measurement system, the
measurement electrodes 14a, 16a in the reaction zone 20 are coupled to
electronic circuitry (typically in a test meter (not shown) into which the
test strip
10 is inserted, as is well known in the art) that supplies an electrical
potential to
the measurement electrodes and measures the response of the electrochemical
sensor to this potential (e.g. current, impedance, charge, etc.). This
response is
proportional to the analyte concentration.
The test meter contacts the test strip 10 at contact pads 14b, 16b in a
contact
zone 22 of the test strip 10. Contact zone 22 is located somewhat remotely
from
measurement zone 20, usually (but not always) at an opposite end of the test
strip 10. Conductive traces 14c, 16c couple the contact pads 14b, 16b in the
contact zone 22 to the respective measurement electrodes 14a,16a in the
reaction zone 20.
Especially for biosensors 10 in which the electrodes, traces and contact pads
are
comprised of electrically conductive thin films (for instance, noble metals,
carbon ink, and silver paste, as non-limiting examples), the resistivity of
the
conductive traces 14c,16c that connect the contact zone 22 to the reaction
zone
20 can amount to several hundred Ohms or more. This parasitic resistance
causes a potential drop along the length of the traces 14c, 16c, such that the
potential presented to the measurement electrodes 14a,16a in the reaction zone
20 is considerably less than the potential applied by the test meter to the
contact
pads 14b, 16b of the test strip 10 in the contact zone 22. Because the
impedance
3
CA 02570186 2009-11-04
of the reaction taking place within the reaction zone 20 can be within an
order
of magnitude of the parasitic resistance of the traces 14c,16c, the signal
being
measured can have a significant offset due to the I-R (current x resistance)
drop
induced by the traces. If this offset varies from test strip to test strip,
then noise
is added to the measurement result. Furthermore, physical damage to the test
strip 10, such as abrasion, cracks, scratches, chemical degradation, etc. can
occur during manufacturing, shipping, storage and/or user mishandling. These
defects can damage the conductive areas 14,16 to the point that they present
an
extremely high resistance or even an open circuit. Such increases in the trace
resistance can prevent the test meter from performing an accurate test.
Thus, a system and method are needed that will allow for confirmation of the
integrity of test strip traces, for measurement of the parasitic resistance of
test
strip traces, and for controlling the potential level actually applied to the
test
strip measurement electrodes in the reaction zone. The present invention is
directed toward meeting these needs.
SUMMARY OF THE INVENTION
The present invention provides a test strip for measuring a signal of interest
in a
biological fluid when the test strip is mated to an appropriate test meter,
wherein
the test strip and the test meter include structures to verify the integrity
of the test
strip traces, to measure the parasitic resistance of the test strip traces,
and to
provide compensation in the voltage applied to the test strip to account for
parasitic resistive losses in the test strip traces.
In one aspect of the invention, there is provided a biosensor system for
detecting
the concentration of an analyte using a biosensor test strip, the system
comprising: a biosensor test strip comprising: a working electrode; a working
electrode trace operatively coupled to the working electrode; a working sense
4
= CA 02570186 2009-11-04
trace operatively coupled to the working electrode (814a); a counter
electrode; a
counter electrode trace operatively coupled to the counter electrode; and a
counter sense trace operatively coupled to the counter electrode; a test meter
having an interface for receiving the biosensor test strip; and a difference
amplifier having first and second difference amplifier inputs and a difference
amplifier output, wherein the first difference amplifier input is operatively
coupled to the working sense trace and the second difference amplifier input
is
operatively coupled to the counter sense trace; and wherein the difference
amplifier output is operatively coupled to the counter electrode trace.
In another aspect of the invention, there is provided a biosensor system
comprising: a biosensor test strip, as described hereinbefore; a test meter
coupled to the biosensor test strip, the test meter comprising: a difference
amplifier having first and second difference amplifier inputs and a difference
amplifier output, wherein the first difference amplifier input is operatively
coupled to the working sense trace and the second difference amplifier input
is
operatively coupled to the counter sense trace; a reference voltage source;
and a
voltage follower amplifier having first and second voltage follower inputs and
a
voltage follower output, wherein the first voltage follower input is coupled
to
the reference voltage source, the second voltage follower input is coupled to
the
difference amplifier output, and the voltage follower output is coupled to the
counter electrode trace.
In still another aspect of the invention, there is provided a method for
applying
a stimulus having a desired magnitude to a biological sample under test in a
measurement cell of a test strip, the method comprising the steps of: applying
a
stimulus to the test strip; measuring a magnitude of a voltage difference that
is
produced across the measurement cell in response to the stimulus; and
adjusting
the magnitude of the stimulus applied to the test strip (800) such that the
voltage
4a
CA 02570186 2009-11-04
difference produced across the measurement cell has substantially the same
magnitude as the desired magnitude.
In still another aspect of the invention, there is provided a method for
making a
measurement of an analyte using a test strip comprising a measurement cell, a
counter electrode, and a working electrode, the method comprising the steps
of:
receiving the test strip into a biosensor device; applying a stimulus to the
counter electrode to produce a potential across the measurement cell;
measuring
the potential difference developed across the measurement cell by the
application of the stimulus; adapting the stimulus applied to the counter
electrode based upon the measured potential difference developed across the
measurement cell.
In yet another aspect of the invention, there is provided a method for
measuring
a parasitic impedance of at least one trace of a biosensor test strip, the
biosensor
test strip being as described hereinbefore; the method comprising the steps
of:
selectively placing a resistor having a known impedance in series with the
working sense trace and working electrode trace to form a series circuit
having a
series circuit impedance comprising the known impedance of the resistor and a
working sense trace impedance and a working electrode trace impedance;
selectively applying a stimulus to produce a current passing through the
series
circuit; measuring the current flowing through the series circuit; using the
current measurement to calculate the parasitic impedance of at least one trace
of
a biosensor test strip.
In a further aspect of the invention, there is provided a method for measuring
a
parasitic impedance of at least one trace of a biosensor test strip, the
biosensor
test strip being as described hereinbefore; the method comprising the steps
of:
selectively placing a resistor having a known impedance in series with the
counter sense trace and counter electrode trace to form a series circuit
having a
4b
= CA 02570186 2009-11-04
series circuit impedance comprising the known impedance of the resistor and a
counter sense trace impedance and a counter electrode trace impedance;
selectively applying a stimulus to produce a current passing through the
series
circuit; measuring the current flowing through the series circuit; and using
the
current measurement to calculate the parasitic impedance of at least one trace
of
a biosensor test strip.
In a further aspect of the invention, there is provided a method for using a
biosensor meter to measure a parasitic impedance of at least one trace of a
1() biosensor test strip, the biosensor test strip being as described
hereinbefore; and
the biosensor meter comprising: a biosensor meter test strip interface
comprising: a working electrode contact pad, a working sense contact pad, a
counter electrode contact pad, and a counter sense contact pad; the method
comprising the steps of: receiving the test strip into the biosensor meter;
operatively coupling the test strip to the biosensor meter test strip
interface such
that the working electrode trace is operatively coupled to the working
electrode
contact pad, the working sense trace is operatively coupled to the working
sense
contact pad, the counter electrode trace is operatively coupled to the counter
electrode contact pad, and the counter sense trace is operatively coupled to
the
counter sense trace; selectively switching a resistor having a known impedance
into series with the working sense trace and working electrode trace to form a
series circuit having a series circuit impedance comprising the known
impedance of the resistor and a working sense trace impedance and a working
electrode trace impedance; providing a stimulus to produce a current passing
through the series circuit; measuring the current flowing through the series
circuit; and using the current measurement to calculate the working electrode
trace (814c) impedance and of the working sense trace impedance.
In a still further aspect of the invention, there is provided a method for
using a
biosensor meter to measure a parasitic impedance of at least one trace of a
4c
= CA 02570186 2009-11-04
biosensor test strip, the biosensor test strip being as described
hereinbefore; and
the biosensor meter comprising: a biosensor meter test strip interface
comprising: a working electrode contact pad, a working sense contact pad, a
counter electrode contact pad, and a counter sense contact pad; the method
comprising the steps of: receiving the test strip into the biosensor meter;
operatively coupling the test strip to the biosensor meter test strip
interface such
that the working electrode trace is operatively coupled to the working
electrode
contact pad, the working sense trace is operatively coupled to the working
sense
contact pad, the counter electrode trace is operatively coupled to the counter
electrode contact pad, and the counter sense trace is operatively coupled to
the
counter sense trace; selectively switching a resistor having a known impedance
in series with the counter sense trace and counter electrode trace to form a
series
circuit having a series circuit impedance comprising the known impedance of
the resistor and a counter sense trace impedance and counter electrode trace
impedance; selectively applying a stimulus to produce a current passing
through
the series circuit; measuring the current flowing through the series circuit;
and
using the current measurement to calculate an indication of the counter sense
trace impedance and counter electrode trace impedance.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be further described, by way of example only, with
reference
to the accompanying drawings, in which:
FIG. 1 is schematic plan view of a typical prior art test strip for use in
measuring
the concentration of an analyte of interest in a biological fluid.
FIG. 2 is a schematic plan view of a first embodiment test strip according to
the
present invention.
FIG. 3 is a schematic diagram of a first embodiment electronic test circuit
for use
with the first embodiment test strip of FIG. 2.
4d
CA 02570186 2009-11-04
FIG. 4 is an exploded assembly view of a second typical test strip for use in
measuring the concentration of an analyte of interest in a biological fluid.
FIG. 5 illustrates a view of an ablation apparatus suitable for use with the
present invention.
FIG. 6 is a view of the laser ablation apparatus of FIG. 5 showing a second
mask.
FIG. 7 is a view of an ablation apparatus suitable for use with the present
invention.
FIG. 8 is a schematic plan view of a second embodiment test strip according to
the present invention.
FIG. 9 is a schematic diagram of a second embodiment electronic test circuit
for
use with the second embodiment test strip of FIG. 8.
FIG. 10 is a schematic diagram of a third embodiment electronic test circuit
for
use with the second embodiment test strip of FIG. 8.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
For the purposes of promoting an understanding of the principles of the
invention, reference will now be made to the embodiment illustrated in the
drawings, and specific language will be used to describe that embodiment. It
will nevertheless be understood that no limitation of the scope of the
invention is
intended. Alterations and modifications in the illustrated device, and further
applications of the principles of the invention as illustrated therein, as
would
normally occur to one skilled in the art to which the invention relates are
contemplated, are desired to be protected. In particular, although the
invention is
discussed in terms of a blood glucose meter, it is contemplated that the
invention
can be used with devices for measuring other analytes and other sample types.
Such alternative embodiments require certain adaptations to the embodiments
discussed herein that would be obvious to those skilled in the art.
5
CA 02570186 2009-11-04
=
Although the system and method of the present invention may be used with test
strips having a wide variety of designs and made with a wide variety of
construction techniques and processes, a first embodiment electrochemical test
strip of the present invention is illustrated schematically in FIG. 2, and
indicated
generally at 200. Portions of test strip 200 which are substantially identical
to
those of test strip 10 are marked with like reference designators. Referring
to
FIG. 2, the test strip 200 comprises a bottom substrate 12 formed from an
opaque piece of 350 1.tm thick polyester (such as Melinex 329, trade-mark,
available from DuPont) coated on its top surface with a 50 nm conductive gold
layer (for instance by sputtering or vapor deposition, by way of non-limiting
example). Electrodes, connecting traces and contact pads therefor are then
patterned in the conductive layer by a laser ablation process. The laser
ablation
process is performed by means of an excimer laser which passes through a
chrome-on-quartz mask. The mask pattern causes parts of the laser field to be
reflected while allowing other parts of the field to pass through, creating a
pattern on the gold which is evaporated where contacted by the laser light.
The
laser ablation process is described in greater detail hereinbelow. For
example,
working 214a, counter 216a, and counter sense 224a electrodes may be formed
as shown and coupled to respective measurement contact pads 214b, 216b and
224b by means of respective traces 214c, 216c and 224c. These contact pads
214b, 216b and 224b provide a conductive area upon the test strip 200 to be
contacted by a connector contact of the test meter (not shown) once the test
strip
200 is inserted into the test meter, as is well known in the art.
FIGs. 2 and 3 illustrate an embodiment of the present invention that improves
upon the prior art test strip designs by allowing for compensation of
parasitic I-
R drop in the counter electrode line of the test strip. It will be appreciated
that
the test strip 200 of FIG. 2 is substantially identical to the prior art test
strip 10
of FIG. 1, except for the addition of the counter sense electrode 224a,
contact
pad 224b, and trace 224c. Provision of the counter sense line 224 allows the
6
CA 02570186 2009-11-04
test meter (as described hereinbelow) to compensate for parasitic resistance
between the contact pads 216b,224b. Note that the embodiment of FIG. 2 when
used with the circuit of FIG. 3 only compensates for the I-R drop on the
counter
electrode side of the test strip 200. Parasitic resistance on the working
electrode
side of the test strip 200 cannot be detected using this circuitry, although
it
could be replicated on the working electrode side if desired, as will be
apparent
to those skilled in the art with reference to the present disclosure. Further
methods for compensating for parasitic resistance on both the working and
counter sides of the test strip are presented hereinbelow. The counter sense
line
of FIG. 2 therefore allows the test meter to compensate for any parasitic
resistance potential drop in the counter line 216, as explained in greater
detail
with respect to FIG. 3.
Referring now to FIG. 3, there is shown a schematic electrical circuit diagram
of
a first embodiment electrode compensation circuit (indicated generally at 300)
housed within the test meter. As indicated, the circuit couples to contact
pads
214b, 216b and 224b when the test strip 200 is inserted into the test meter.
As
will be appreciated by those skilled in the art, a voltage potential is
applied to
the counter electrode contact pad 216b, which will produce a current between
.. the counter electrode 216a and the working electrode 214a that is
proportional
to the amount of analyte present in the biological sample applied to the
reagent
18. The current from working electrode 214a is transmitted to working
electrode contact pad 214b by means of working electrode trace 214c and
provided to a current-to-voltage amplifier 310. The analog output voltage of
amplifier 310 is converted to a digital signal by analog-to-digital converter
(A/D) 312. This digital signal is then processed by microprocessor 314
according to a previously stored program in order to determine the
concentration of analyte within the biological sample applied to the test
strip
200. This concentration is displayed to the user by means of an appropriate
output device 316, such as a liquid crystal display (LCD) screen.
7
A CA 02570186 2009-11-04
Microprocessor 314 also outputs a digital signal indicative of the voltage
potential to be applied to the counter electrode contact pad 216b. This
digital
signal is converted to an analog voltage signal by digital-to-analog converter
(D/A) 318. The analog output of D/A 318 is applied to a first input of an
operational amplifier 320. A second input of the operational amplifier 320 is
coupled to counter sense electrode contact pad 224b. The output of operational
amplifier 320 is coupled to the counter electrode contact pad 216b.
Operational amplifier 320 is connected in a voltage follower configuration, in
which the amplifier will adjust its output (within its physical limits of
operation)
until the voltage appearing at its second input is equal to the commanded
voltage appearing at its first input. The second input of operational
amplifier
320 is a high impedance input, therefore substantially no current flows in
counter sense line 224. Since substantially no current flows, any parasitic
resistance in counter sense line 224 will not cause a potential drop, and the
voltage appearing at the second input of operational amplifier 320 is
substantially the same as the voltage at counter sense electrode 224a, which
is in
turn substantially the same as the voltage appearing at counter electrode 216a
due to their close physical proximity. Operational amplifier 320 therefore
acts
to vary the voltage potential applied to the counter electrode contact pad
216b
until the actual voltage potential appearing at the counter electrode 216a (as
fed
back over counter sense line 224) is equal to the voltage potential commanded
by the microprocessor 314. Operational amplifier 320 therefore automatically
compensates for any potential drop caused by the parasitic resistance in the
counter electrode trace 216c, and the potential appearing at the counter
electrode
216a is the desired potential. The calculation of the analyte concentration in
the
biological sample from the current produced by the working electrode is
therefore made more accurate, since the voltage that produced the current is
indeed the same voltage commanded by the microprocessor 314. Without the
compensation for parasitic resistance voltage drops provided by the circuit
300,
7a
CA 02570186 2009-11-04
the microprocessor 314 would analyze the resulting current under the mistaken
presumption that the commanded voltage was actually applied to the counter
electrode 216a.
Many methods are available for preparing test strips having multiple
electrodes,
such as carbon ink printing, silver paste silk-screening, scribing metalized
plastic, electroplating, chemical plating, and photo-chemical etching, by way
of
non-limiting example. One preferred method of preparing a test strip having
additional electrode sense lines as described herein is by the use of laser
ablation techniques. Examples of the use of these techniques in preparing
electrodes for biosensors are described in US 7437398, "Biosensors with Laser
Ablation Electrodes with a Continuous Coverlay Channel", and in US 6662439
entitled "Laser Defined Features for Patterned Laminates and Electrode." Laser
ablation is particularly useful in preparing test strips according to the
present
invention because it allows conductive areas having extremely small feature
sizes to be accurately manufactured in a repeatable manner. Laser ablation
provides a means for adding the extra sense lines of the present invention to
a
test strip without increasing the size of the test strip.
It is desirable in the present invention to provide for the accurate placement
of
the electrical components relative to one another and to the overall
biosensor.
In a preferred embodiment, the relative placement of components is achieved,
at
least in part, by the use of broad field laser ablation that is performed
through a
mask or other device that has a precise pattern for the electrical components.
.. This allows accurate positioning of adjacent edges, which is further
enhanced by
the close tolerances for the smoothness of the edges.
7b
CA 02570186 2009-11-04
Figure 4 illustrates a simple biosensor 401 useful for illustrating the laser
ablation process of the present invention, including a substrate 402 having
formed thereon conductive material 403 defining electrode systems comprising
a first electrode set 404 and a second electrode set 405, and corresponding
traces
406, 407 and contact pads 408, 409, respectively. Note that the biosensor 401
is
used herein for purposes of illustrating the laser ablation process, and that
it is
not shown as incorporating the sense lines of the present invention. The
conductive material 403 may contain pure metals or alloys, or other materials,
which are metallic conductors. Preferably, the conductive material is
absorptive
at the wavelength of the laser used to form the electrodes and of a thickness
amenable to rapid and precise processing. Non-limiting examples include
aluminum, carbon, copper, chromium, gold, indium tin oxide (ITO), palladium,
platinum, silver, tin oxide/gold, titanium, mixtures thereof, and alloys or
metallic compounds of these elements. Preferably, the conductive material
includes noble metals or alloys or their oxides. Most preferably, the
conductive
material includes gold, palladium, aluminum, titanium, platinum, ITO and
chromium. The conductive material ranges in thickness from about 10 nm to 80
nm, more preferably, 30 nm to 70 nm, and most preferably
8
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
50 nm. It is appreciated that the thickness of the conductive material depends
upon the
transmissive property of the material and other factors relating to use of the
biosensor.
While not illustrated, it is appreciated that the resulting patterned
conductive material can be
coated or plated with additional metal layers. For example, the conductive
material may be
copper, which is then ablated with a laser into an electrode pattern;
subsequently, the copper
may be plated with a titanium/tungsten layer, and then a gold layer, to form
the desired
electrodes. Preferably, a single layer of conductive material is used, which
lies on the base
402. Although not generally necessary, it is possible to enhance adhesion of
the conductive
material to the base, as is well known in the art, by using seed or ancillary
layers such as
chromium nickel or titanium. In preferred embodiments, biosensor 401 has a
single layer of
gold, palladium, platinum or ITO.
Bio sensor 401 is illustratively manufactured using two apparatuses 10, 10',
shown in Figures
5, 6 and 7, respectively. It is appreciated that unless otherwise described,
the apparatuses 410,
410' operate in a similar manner. Referring first to Figure 5, biosensor 401
is manufactured by
feeding a roll of ribbon 420 having an 80 nm gold laminate, which is about 40
mm in width,
into a custom fit broad field laser ablation apparatus 410. The apparatus 410
comprises a laser
source 411 producing a beam of laser light 412, a chromium-plated quartz mask
414, and
optics 416. It is appreciated that while the illustrated optics 416 is a
single lens, optics 416 is
preferably a variety of lenses that cooperate to make the light 412 in a pre-
determined shape.
A non-limiting example of a suitable ablation apparatus 410 (Figures 5-6) is a
customized
MicrolineLaser 200-4 laser system commercially available from LPKF Laser
Electronic
GmbH, of Garbsen, Germany, which incorporates an LPX-400, LPX-300 or LPX-200
laser
system commercially available from Lambda Physik AG, Gottingen, Germany and a
chromium-plated quartz mask commercially available from International
Phototool Company,
Colorado Springs, Co.
For the MicrolineLaser 200-4 laser system (Figures 5-6), the laser source 411
is a LPX-200
KrF-UV-laser. It is appreciated, however, that higher wavelength UV lasers can
be used in
accordance with this disclosure. The laser source 411 works at 248nm, with a
pulse energy of
600mJ, and a pulse repeat frequency of 50 Hz. The intensity of the laser beam
412 can be
9
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
infinitely adjusted between 3% and 92% by a dielectric beam attenuator (not
shown). The
beam profile is 27x15mm2 (0.62 sq. inch) and the pulse duration 25ns. The
layout on the mask
414 is homogeneously projected by an optical elements beam expander,
homogenizer, and
field lens (not shown). The performance of the homogenizer has been determined
by
measuring the energy profile. The imaging optics 416 transfer the structures
of the mask 414
onto the ribbon 420. The imaging ratio is 2:1 to allow a large area to be
removed on the one
hand, but to keep the energy density below the ablation point of the applied
chromium mask on
the other hand. While an imaging of 2:1 is illustrated, it is appreciated that
the any number of
alternative ratios are possible in accordance with this disclosure depending
upon the desired
design requirements. The ribbon 420 moves as shown by arrow 425 to allow a
number of
layout segments to be ablated in succession.
The positioning of the mask 414, movement of the ribbon 420, and laser energy
are computer
controlled. As shown in Figure 5, the laser beam 412 is projected onto the
ribbon 420 to be
ablated. Light 412 passing through the clear areas or windows 418 of the mask
414 ablates the
metal from the ribbon 420. Chromium coated areas 424 of the mask 414 blocks
the laser light
412 and prevent ablation in those areas, resulting in a metallized structure
on the ribbon 420
surface. Referring now to Figure 6, a complete structure of electrical
components may require
additional ablation steps through a second mask 414'. It is appreciated that
depending upon
the optics and the size of the electrical component to be ablated, that only a
single ablation
step or greater than two ablation steps may be necessary in accordance with
this disclosure.
Further, it is appreciated that instead of multiple masks, that multiple
fields may be formed on
the same mask in accordance with this disclosure.
Specifically, a second non-limiting example of a suitable ablation apparatus
410' (Figure 7) is
a customized laser system commercially available from LPKF Laser Electronic
GmbH, of
Garbsen, Germany, which incorporates a Lambda STEEL (Stable energy eximer
laser) laser
system commercially available from Lambda Physik AG, Gottingen, Germany and a
chromium-plated quartz mask commercially available from International
Phototool Company,
Colorado Springs, Co. The laser system features up to 1000 mJ pulse energy at
a wavelength
of 308 nm. Further, the laser system has a frequency of 100 Hz. The apparatus
410' may be
formed to produce biosensors with two passes as shown in Figures 5 and 6, but
preferably its
optics permit the formation of a 10x40 mm pattern in a 25 ns single pass.
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
While not wishing to be bound to a specific theory, it is believed that the
laser pulse or beam
412 that passes through the mask 414, 414', 414" is absorbed within less than
1 pm of the
surface 402 on the ribbon 420. The photons of the beam 412 have an energy
sufficient to
cause photo-dissociation and the rapid breaking of chemical bonds at the
metal/polymer
interface. It is believed that this rapid chemical bond breaking causes a
sudden pressure
increase within the absorption region and forces material (metal film 403) to
be ejected from
the polymer base surface. Since typical pulse durations are around 20-25
nanoseconds, the
interaction with the material occurs very rapidly and thermal damage to edges
of the
conductive material 403 and surrounding structures is minimized. The resulting
edges of the
electrical components have high edge quality and accurate placement as
contemplated by the
present invention.
Fluence energies used to remove or ablate metals from the ribbon 420 are
dependent upon the
material from which the ribbon 420 is formed, adhesion of the metal film to
the base material,
the thickness of the metal film, and possibly the process used to place the
film on the base
material, i.e. supporting and vapor deposition. Fluence levels for gold on
KALADEX range
from about 50 to about 90 mJ/cm2, on polyimide about 100 to about 120 mJ/cm2,
and on
MELINEX6 about 60 to about 120 mJ/cm2. It is understood that fluence levels
less than or
greater than the above mentioned can be appropriate for other base materials
in accordance
with the disclosure.
Patterning of areas of the ribbon 420 is achieved by using the masks 414,
414'. Each mask
414, 414' illustratively includes a mask field 422 containing a precise two-
dimensional
illustration of a pre-determined portion of the electrode component patterns
to be formed.
Figure 5 illustrates the mask field 422 including contact pads and a portion
of traces. As
shown in Figure 6, the second mask 414' contains a second corresponding
portion of the traces
and the electrode patterns containing fingers. As previously described, it is
appreciated that
depending upon the size of the area to be ablated, the mask 414 can contain a
complete
illustration of the electrode patterns (Figure 7), or portions of patterns
different from those
illustrated in Figures 5 and 6 in accordance with this disclosure. Preferably,
it is contemplated
that in one aspect of the present invention, the entire pattern of the
electrical components on
the test strip are laser ablated at one time, i.e., the broad field
encompasses the entire size of
11
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
the test strip (Figure 7). In the alternative, and as illustrated in Figures 5
and 6, portions of the
entire biosensor are done successively.
While mask 414 will be discussed hereafter, it is appreciated that unless
indicated otherwise,
the discussion will apply to masks 414', 414" as well. Referring to Figure 5,
areas 424 of the
mask field 422 protected by the chrome will block the projection of the laser
beam 412 to the
ribbon 420. Clear areas or windows 418 in the mask field 422 allow the laser
beam 412 to
pass through the mask 414 and to impact predetermined areas of the ribbon 420.
As shown in
Figure 5, the clear area 418 of the mask field 422 corresponds to the areas of
the ribbon 420
from which the conductive material 403 is to be removed.
Further, the mask field 422 has a length shown by line 430 and a width as
shown by line 432.
Given the imaging ratio of 2:1 of the LPX-200, it is appreciated that the
length 30 of the mask
is two times the length of a length 434 of the resulting pattern and the width
432 of the mask is
two times the width of a width 436 of the resulting pattern on ribbon 420. The
optics 416
reduces the size of laser beam 412 that strikes the ribbon 420. It is
appreciated that the
relative dimensions of the mask field 422 and the resulting pattern can vary
in accordance with
this disclosure. Mask 414' (Figure 6) is used to complete the two-dimensional
illustration of
the electrical components.
Continuing to refer to Figure 5, in the laser ablation apparatus 410 the
excimer laser source
411 emits beam 412, which passes through the chrome-on-quartz mask 414. The
mask field
422 causes parts of the laser beam 412 to be reflected while allowing other
parts of the beam
to pass through, creating a pattern on the gold film where impacted by the
laser beam 412. It
is appreciated that ribbon 420 can be stationary relative to apparatus 410 or
move continuously
on a roll through apparatus 410. Accordingly, non-limiting rates of movement
of the ribbon
420 can be from about 0 m/min to about 100 m/min, more preferably about 30
m/min to about
60 m/min. It is appreciated that the rate of movement of the ribbon 420 is
limited only by the
apparatus 410 selected and may well exceed 100 m/min depending upon the pulse
duration of
the laser source 411 in accordance with the present disclosure.
Once the pattern of the mask 414 is created on the ribbon 420, the ribbon is
rewound and fed
through the apparatus 410 again, with mask 414' (Figure 6). It is appreciated,
that
12
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
alternatively, laser apparatus 410 could be positioned in series in accordance
with this
disclosure. Thus, by using masks 414, 414', large areas of the ribbon 420 can
be patterned
using step-and-repeat processes involving multiple mask fields 422 in the same
mask area to
enable the economical creation of intricate electrode patterns and other
electrical components
on a substrate of the base, the precise edges of the electrode components, and
the removal of
greater amounts of the metallic film from the base material.
The second embodiment of the present invention illustrated in FIGs. 8 and 9
improve upon the
prior art by providing for I-R drop compensation of both the working and
counter electrode
leads on the test strip. Referring now to FIG. 8, there is schematically
illustrated a second
embodiment test strip configuration of the present invention, indicated
generally at 800. The
test strip 800 comprises a bottom substrate 12 coated on its top surface with
a 50 nm
conductive gold layer (for instance by sputtering or vapor deposition, by way
of non-limiting
example). Electrodes, connecting traces and contact pads therefor are then
patterned in the
conductive layer by a laser ablation process as described hereinabove. For
example, working
814a, working sense 826a, counter 216a, and counter sense 224a electrodes may
be formed as
shown and coupled to respective measurement contact pads 814b, 826b, 216b and
224b by
means of respective traces 814c, 826c, 216c and 224c. These contact pads 814b,
826b, 216b
and 224b provide a conductive area upon the test strip 800 to be contacted by
a connector
contact of the test meter (not shown) once the test strip 800 is inserted into
the test meter.
It will be appreciated that the test strip 800 of FIG. 8 is substantially
identical to the first
embodiment test strip 200 of FIG. 2, except for the addition of the working
sense electrode
826a, contact pad 826b, and trace 826c. Provision of the working sense line
826 allows the
test meter to compensate for any I-R drop caused by the contact resistance of
the connections
to the contact pads 814b and 216b, and to compensate for the trace resistance
of traces 814c
and 216c.
Referring now to FIG. 9, there is shown a schematic electrical circuit diagram
of a second
embodiment electrode compensation circuit (indicated generally at 900) housed
within the test
meter. As indicated, the circuit couples to contact pads 826b, 814b, 216b and
224b when the
test strip 800 is inserted into the test meter. As will be appreciated by
those skilled in the art, a
voltage potential is applied to the counter electrode contact pad 216b, which
will produce a
13
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
current between the counter electrode 216a and the working electrode 814a that
is proportional
to the amount of analyte present in the biological sample applied to the
reagent 18. The
current from working electrode 814a is transmitted by working electrode trace
814c to
working electrode contact pad 814b and provided to current-to-voltage
amplifier 310. The
analog output voltage of amplifier 310 is converted to a digital signal by A/D
312. This digital
signal is then processed by microprocessor 314 according to a previously
stored program in
order to determine the concentration of the analyte of interest within the
biological sample
applied to the test strip 800. This concentration is displayed to the user by
means of LCD
output device 316.
Microprocessor 314 also outputs a digital signal indicative of the voltage
potential to be
applied to the counter electrode contact pad 216b. This digital signal is
converted to an analog
voltage signal by D/A 318 (reference voltage source). The analog output of D/A
318 is
applied to a first input of an operational amplifier 320. A second input of
the operational
amplifier 320 is coupled to an output of operational amplifier 910.
Operational amplifier 910
is connected in a difference amplifier configuration using an instrumentation
amplifier. A first
input of operational amplifier 910 is coupled to working sense electrode
contact pad 826b,
while a second input of operational amplifier 910 is coupled to counter sense
electrode contact
pad 224b. The output of operational amplifier 320 is coupled to the counter
electrode contact
pad 216b. When the biosensor test strip (800) is coupled to a test meter a
first input of the
operational amplifier 910 operatively coupled to the working sense trace 826c
and a second
input is operatively coupled to the counter sense trace 224c. The output of
the operational
amplifier is operatively coupled to the counter electrode trace. The
operational amplifier 910
in this configuration works as a difference amplifier.
Operational amplifier 320 is connected in a voltage follower configuration, in
which the
amplifier will adjust its output (within its physical limits of operation)
until the voltage
appearing at its second input is equal to the commanded voltage appearing at
its first input.
Both inputs of operational amplifier 910 are high impedance inputs, therefore
substantially no
.. current flows in counter sense line 224 or working sense line 826. Since
substantially no
current flows, any parasitic resistance in counter sense line 224 or working
sense line 826 will
not cause a potential drop, and the voltage appearing across the inputs of
operational amplifier
910 is substantially the same as the voltage across the measurement cell (i.e.
across counter
14
CA 02570186 2006-12-12
WO 2005/124331 PCT/EP2005/006618
electrode 216a and working electrode 814a). Because operational amplifier 910
is connected
in a difference amplifier configuration, its output represents the voltage
across the
measurement cell.
Operational amplifier 320 will therefore act to vary its output (i.e. the
voltage potential applied
to the counter electrode contact pad 216b) until the actual voltage potential
appearing across
the measurement cell is equal to the voltage potential commanded by the
microprocessor 314.
Operational amplifier 320 therefore automatically compensates for any
potential drop caused
by the parasitic resistance in the counter electrode trace 216c, counter
electrode contact 216b,
working electrode trace 814c, and working electrode contact 814b, and
therefore the potential
appearing across the measurement cell is the desired potential. The
calculation of the analyte
concentration in the biological sample from the current produced by the
working electrode is
therefore made more accurate.
FIG. 10, in conjunction with FIG. 8, illustrates a third embodiment of the
present invention
that improves over the prior art by providing I-R drop compensation for both
the working and
counter electrode lines, as well as providing verification that the resistance
of both the
working and counter electrode lines is not above a predetermined threshold in
order to assure
that the test meter is able to compensate for the I-R drops. Referring now to
FIG. 10, there is
shown a schematic electrical circuit diagram of a third embodiment electrode
compensation
circuit (indicated generally at 1000) housed within the test meter. The
electrode compensation
circuit 1000 works with the test strip 800 of FTG. 8. As indicated, the
circuit couples to
contact pads 826b, 814b, 216b and 224b when the test strip 800 is inserted
into the test meter.
As will be appreciated by those skilled in the art, a voltage potential is
applied to the counter
electrode contact pad 216b, which will produce a current between the counter
electrode 216a
and the working electrode 814a that is proportional to the amount of analyte
present in the
biological sample applied to the reagent 18. The current from working
electrode 814a is
transmitted to working electrode contact pad 814b by working electrode trace
814c and
provided to current-to-voltage amplifier 310. The output of current-to-voltage
amplifier 310 is
applied to the input of instrumentation amplifier 1002 which is configured as
a buffer having
unity gain when switch 1004 in the closed position. The analog output voltage
of amplifier
1002 is converted to a digital signal by A/D 312. This digital signal is then
processed by
microprocessor 314 according to a previously stored program in order to
determine the
CA 02570186 2009-11-04
concentration of analyte within the biological sample applied to the test
strip
800. This concentration is displayed to the user by means of LCD output device
316.
Microprocessor 314 also outputs a digital signal indicative of the voltage
potential to be applied to the counter electrode contact pad 216b. This
digital
signal is converted to an analog voltage signal by D/A 318. The analog output
of D/A 318 is applied to the input of an operational amplifier 320 that is
configured as a voltage follower when switch 1006 is in the position shown.
The
output of operational amplifier 320 is coupled to the counter electrode
contact
pad 216b, which will allow measurement of a biological fluid sample applied to
the reagent 18. Furthermore, with switches 1006, 1008 and 1010 positioned as
illustrated in FIG. 10, the circuit is configured as shown in FIG. 9 and may
be
used to automatically compensate for parasitic and contact resistance as
described hereinabove with respect to FIG. 9.
In order to measure the amount of parasitic resistance in the counter
electrode
line 216, switch 1008 is placed in the position shown in FIG. 10, switch 1006
is
placed in the position opposite that shown in FIG. 10, while switch 1010 is
closed. The operational amplifier 320 therefore acts as a buffer with unity
gain
and applies a voltage potential to counter electrode contact pad 216b through
a
known resistance Rwm. This resistance causes a current to flow in the counter
electrode line 216 and the counter sense line 224 that is sensed by current-to-
voltage amplifier 310, which is now coupled to the current sense line through
switch 1010. The output of current-to-voltage amplifier 310 is provided to the
microprocessor 314 through AID 312. Because the value of Rnõ,õ is known, the
microprocessor 314 can calculate the value of any parasitic resistance in the
counter sense line 224 and the counter electrode line 216. This parasitic
resistance value can be compared to a predetermined threshold stored in the
test
meter to determine if physical damage has occurred to the test strip 800 or if
16
CA 02570186 2009-11-04
I.
nonconductive buildup is present on the contact pads to such an extent that
the
test strip 800 cannot be reliably used to perform a test. In such situations,
the
test meter may be programmed to inform the user that an alternate test strip
should be inserted into the test meter before proceeding with the test.
In order to measure the amount of parasitic resistance in the working
electrode
line 814, switches 1006 and 1008 are placed in the position opposite that
shown
in FIG. 10, while switch 1010 is opened. The operational amplifier 320
therefore acts as a buffer with unity gain and applies a voltage potential to
working sense contact pad 826b through a known resistance Rõõõ,. This
resistance causes a current to flow in the working sense line 826 and the
working electrode line 814 that is sensed by current-to-voltage amplifier 310.
The output of current-to-voltage amplifier 310 is provided to the
microprocessor
314 through A/D 312. Because the value of Rnom is known, the microprocessor
314 can calculate the value of any parasitic resistance in the working sense
line
826 and the working electrode line 814. This parasitic resistance value can be
compared to a predetermined threshold stored in the test meter to determine if
physical damage has occurred to the test strip 800 or if nonconductive buildup
is
present on the contact pads to such an extent that the test strip 800 cannot
be
reliably used to perform a test. In such situations, the test meter may be
programmed to inform the user that an alternate test strip should be inserted
into
the test meter before proceeding with the test.
While the invention has been illustrated and described in detail in the
drawings
and foregoing description, the description is to be considered as illustrative
and
not restrictive in character. Only the preferred embodiment, and certain other
embodiments deemed helpful in further explaining how to make or use the
preferred embodiment, have been shown. All changes and modifications that
come within the spirit of the invention are desired to be protected.
17
