Patent Application
20200033287
The present invention relates to a method of constructing a universal test strip structure and operation thereof, and more particularly, a method of constructing a universal test strip structure made compatible with various electrochemical detections by using an identification mechanism and operation thereof.
Electrochemical biosensors are used to determine the concentration of various analytes from samples. The analytes may include glucose, uric acid and cholesterol of biological fluids. When testing samples, the test strip may be inserted into a meter, and the sample may be a liquid dropped in the reaction chamber of the test strip to determine the concentration of the analyte in the sample.
According to the development trend in the biosensor market, the demand for multifunctional biosensor is increasing. In other words, the demand of various detection tests including glucose, uric acid and/or cholesterol combined in one meter is increasing. In order to develop a multifunctional biosensor, there are several technical problems that need to be addressed. The technical problems include developing a universal test strip having a structure that can fit to one meter having different settings for measuring different analytes, identifying a specific type of analyte to be tested before performing a test, developing a universal test strip that does not exceed an ideal tolerance for various detecting voltages or detecting currents for different analytes, and developing a structure of a universal test strip having a small reaction chamber that can still generate an accurate result even when the detecting voltages or detecting currents exceed the ideal tolerance.
By developing a universal test strip, manufacturing cost may be reduced. Possible reasons to exceed the ideal tolerance of electrode include the high concentration of the analyte, insufficient sample volume to be able to cover desired area of the electrodes in the reaction chamber, the counter electrode is reduced to be as small as possible causing the reaction area to be reduced, combination of positive and negative voltages between the working electrode and the reference electrode, or burn-off caused by electrochemical procedure. Exceeding the ideal tolerance of an electrode (usually happened on the counter electrode) may damage the effective reaction area for following steps. The damages include the electrode surface being denatured, sediment on the reaction area, sample electrolysis, or reaction air bubbles over the electrode surface. If the effective reaction area is damaged, the following detection may have inaccurate result. Therefore, a universal test strip that can identify the type of test strip needed and to avoid damage in the electrodes that will influence following detections is needed to be developed.
In recent years, there are a growing number of diabetic patients. Glucose concentration monitoring is important in the everyday life for diabetic patents. Routine tests must be conducted at least 3-4 times every day. According to the concentration of blood glucose, the glucose concentration may be controlled using insulin. This will reduce the risk of medical complications such as vision loss and kidney failure. The accurate measurement of blood glucose concentration is needed.
In the past, meters may use test strips having a counter electrode but without a reference electrode. As compared to having both the counter electrode and the reference electrode, the stability and accuracy of the test tube are reduced when the reference electrode is not in use. Therefore, conventional meters may use test strips having separate reference electrode and counter electrode. The electrodes are layers of conductive material formed on a substrate of the test strip. When a sample is introduced to a test strip, a chemical reaction is performed on the reaction chamber of the test strip. The reaction chamber exposes parts of the three electrodes to the sample. The current across the working electrode and the counter electrode is determined according to the concentration of the analyte. The additional electrode needed to be placed within the reaction chamber of the test strip causes the increase in the area of the reaction chamber. The objective is to accurately measure the concentration of an analyte from a small sample.
The increase in the area of the reaction chamber due to the addition of an electrode would require the volume of the sample to increase. Thus, there is a need to develop a technology wherein only a small sample is needed to accurately measure the concentration of the analyte of the sample. When the voltage or current density across the working electrode and the counter electrode is too high, the characteristics or situation of the counter electrode surface may be permanently or temporarily changed. For example, when the current is too high, the surface area of the counter electrode may not be able to receive the instantaneous current and form an overcurrent. In some circumstances, a reading of the current on the second set of voltage applied may be required. This means that a second set of voltage need to be supplied to the test strip. Because the counter electrode may have been damaged during the supply of the first set of voltage supplied to the test strip, the accuracy of the reading may be uncertain due to unknown damage of the test strip during the first voltage applied. Thus, there is a need to develop a method of operation of a meter that would ensure an accurate readout of the current to measure the concentration of the analyte in the sample.
An embodiment of the present invention presents a method of operation of a meter. The method comprises placing a sample on a reaction chamber of a test strip of the meter, assigning a first electrode of the test strip to be a counter electrode, applying a first signal to a working electrode of the test strip during a first period of time, assigning a second electrode of the test strip to be the counter electrode, applying a second signal to the working electrode of the test strip during a second period of time, and measuring a current across the working electrode and the second electrode to determine a concentration of an analyte of the sample during the second period of time. The method of operation of a meter can be controlled and performed by a microprocessor control unit (MCU) in the meter. The method is to ensure when the voltage applied to the test strip more than one time, an upcoming reading can use an undamaged electrode as a counter electrode for the accuracy of the reading. Therefore, the method may ensure the accuracy of an upcoming reading.
Another embodiment of the present invention presents a structure of a test strip. The test strip comprises a substrate, a working electrode formed on the substrate, a reference electrode formed on the substrate, and a counter electrode formed on the substrate. The working electrode has a plurality of resistor blocks. The plurality of resistor blocks are disposed separately from each other and only coupled to each other in series.
These and other objectives of the present invention will no doubt become obvious to those of ordinary skill in the art after reading the following detailed description of the preferred embodiment that is illustrated in the various figures and drawings.
Step 101: place a sample on a reaction chamber of a test strip of the meter;
Step 102: assign a first electrode of the test strip to be a counter electrode;
Step 103: apply a first signal to a working electrode of the test strip during a first period of time;
Step 104: assign a second electrode of the test strip to be the counter electrode;
Step 105: apply a second signal to the working electrode of the test strip during a second period of time; and
Step 106: measure a response according to the second signal.
In step 101, the sample may be placed inside the reaction chamber of the test strip of the meter.
In step 102, a first electrode of the at least three electrodes 201, 202, and 203 of the test strip 200 shown in
The counter electrode 203 (also called the auxiliary electrode) may be used to balance the current between the working electrode 201 and the counter electrode 203, or so define the reactions in which an electric current is expected to flow. The reference electrode 202 is an electrode which has a stable and well-known electrode potential, which may be used to provide a stable voltage difference between the working electrode 201 and the reference electrode 202. The working electrode 201 is the electrode in the electrochemical system on which the reaction of interest is occurring. The embodiment may only be one working electrode 201 to reduce the reaction area needed. Some embodiments of a test strip may have more than one working electrode 201. For example, there may be two working electrodes 201.
Each of the working electrodes 201 may be covered with different enzyme (or one of the working electrodes 201 without covering enzyme) for different testing. When the working electrode 201 of a test strip is set to only be used for one type of testing, the test strip may be manufactured to only have one working electrode 201. In doing so, no need for additional working electrode 201 could reduce the area for the reaction chamber. The test strips are mainly designed to have the sample to mainly cover the working electrode 201. The coverage of the sample on the counter electrode 203 is relatively ignored. Thus, the working electrode 201 may be designed to be able to handle the voltage or current supplied and is not likely to be damaged during testing process.
The working electrode 201 may be coupled to two pads 301 and 304. A pad 302 may be coupled to the reference electrode 202. A pad 303 may be coupled to the counter electrode 203. The reference electrode 202 can be a counter electrode 203 during the first period of time, and it can be the reference electrode 202 during the second period of time. The pads 301, 302, 303, and 304 may be used to couple the test strip 200 to a readout circuit of the meter. Furthermore, the working electrode 201 may further comprise a plurality of resistor blocks 305 coupled to each other. The at least three electrodes 201, 202, and 203 and the pads 301, 302, 303, and 304 may be formed on the substrate 204 using a first conductive material. The first conductive material may be a carbon black. The at least three electrodes 201, 202, and 203 are not limited to being formed using carbon black. In some other embodiments, the at least three electrodes 201, 202, and 203 may be formed using other conductive materials.
Furthermore, a conductive layer of a second conductive material may be formed on the substrate 204 before forming the working electrode 201 and the second electrode 203. The second conductive material may have higher conductivity than the first conductive material. As shown in
When a resistor block is formed on the substrate, the plurality of resistor blocks may initially all be low resistance blocks L. Each of the low resistance blocks L may have a quadrilateral shape. According to the needs of the meter, a number of the low resistance blocks L may be transformed to be high resistance blocks H. A low resistance blocks L may be transformed to be a high resistance block H by removing a part of one side of the low resistance blocks L as shown in
The resistance of a resistor block may be determined according to the distance of path traveled by the current through the resistor block. Since a part of the low resistance blocks L are removed to form the high resistance blocks H, the shortest path through the working electrode has been removed. The shortest path may be removed using a laser ablation process wherein the conductive layer the low resistance block L forming the shortest path may be partially of fully removed.
Initially, the two resistors R are coupled in parallel. According to the need of the meter, the low resistance block L may be converted to be a high resistance block H. A part of one of the connecting wires connecting the two resistors R in parallel may be removed using laser ablation process. The two resistors R may then be connected in series as shown in
RAB=(n)RH+[(N-n)RL] (1)
where:
RAB is the total resistance of the plurality of resistor blocks;
n is the number of the high resistance blocks;
RH is the resistance of one high resistance block;
N is the total number of the plurality of resistor blocks; and
RL is the resistance of one low resistance block.
The plurality of resistor blocks may not be limited to being disposed on the working electrode. The plurality of resistor blocks may be disposed in any conductive path that forms a loop to the meter. However, for the present invention, only the conductive path of the working electrode forms a loop to the meter. The main reason for having the plurality of resistor blocks be formed on the working electrode is that the working electrode has two ends coupled to the meter to form the loop while other electrodes only have one end coupled to the meter. To reduce the number of connections between the test strip and the meter, the use of available electrodes may be optimized by being used for more than one purpose. An electrode such as the working electrode may have a dual purpose since the resistance of the resistor blocks does not affect the output of the testing because the current flowing through the working electrode is close to zero. The reason for the working electrode to be the only electrode in test strip to have two ends coupled to the meter is that, in coordination with the sensing circuit of the meter, the current and bias voltage supplied to the test strip are separate from each other to reduce the resistance of the silver layer. Thus, the bias voltages required during testing may be stabilized.
In the same way as the test strip 200 shown in
In some embodiments of the present invention, the working electrode 801 of the test strips 800 in
The first counter electrode 803 is damaged during the first period time. The damage in the first counter electrode 803 may be caused by insufficient size of the reaction area but still plays the role of a counter electrode during the first period of time. While the area of the first counter electrode 803 may be limited in the reaction chamber, the second counter electrode 804 may have an area that is sufficient for accurate measurement. Since different electrodes are the counter electrodes at different periods of time, the first counter electrode 803 and the second counter electrode 804 may have separate paths for connecting to the meter. As the voltage levels applied, conductivity of each counter electrode, or the reacted analyte during two periods of time may be varied, the area of the second counter electrode 804 may or may not be larger than the first counter electrode.
In step 103 (
Due to the concentration of the analyte in the sample, the current density flowing across the working electrode and the counter electrode may be too high. Under the above-mentioned circumstance, the characteristics of the counter electrode may temporarily or permanently change. Thus, in step 104, the second electrode of the at least three electrodes may be assigned to be the counter electrode.
Since the reference electrode may be used to provide a fixed potential difference between the working electrode and the reference electrode, there is little or no current flowing through the reference electrode during the first period of time. The reference electrode may not be damaged due to high current density. Therefore, for the proceeding steps of the method, the electrode originally assigned to be the reference electrode may be assigned to be the new counter electrode. And, the electrode originally assigned to be the counter electrode may be assigned to be the new reference electrode. In some other embodiments, for the test strip having four electrodes, the second counter electrode may be used as the counter electrode in the proceeding steps after step 103. The step 103 may be performed regardless of the state of the original counter electrode to ensure that the meter will work properly and be able to accurately determine the concentration of the analyte in the sample when measured after applied the second signal.
When using the test strip shown in
In some embodiments of the present invention, the internal circuit of the meter may comprise of at least one switch used to interchange the connection of the internal circuit to the at least three electrodes of the test strip, wherein the at least one switch may be a solid switch or switch controlled by a microcontroller. The at least one switch may be used to switch the reference electrode used in the first time period to be the counter electrode used in the second time period and switch the counter electrode used in the first time period to be the reference electrode used in the second time period. In some other embodiment, the at least one switch may be used to switch the another counter electrode in the first time period to be the counter electrode used in the second time period.
In step 105, a second signal may be applied to the working electrode of the test strip during the second period of time. The second signal may be a positive signal applied to the working electrode of the test strip. In step 106, a second current may be measured between the working electrode and the current counter electrode to indicate the concentration of the analyte in the sample. In some embodiments, the concentration of the analyte in the sample may be determined by calculating a diffusion factor according to the second current. The diffusion factor is, in turn, used to correct the initial reading of the concentration generated according to the first current.
Furthermore, to ensure that the reading of the second electrode is correct, the area of the counter electrode in the reaction chamber must be greater than the area of the working electrode in the reaction chamber when other conditions are the same. If the area of the counter electrode in the reaction chamber is less than the area of the working electrode in the reaction chamber, the conductivity of the counter electrode must be better than the conductivity of the working electrode when other conditions are the same. The second counter electrode may be set to be in closer proximity to the sampling port as compared to the first counter electrode to ensure that the area of the second counter electrode covered by the sample is sufficient.
The signal applied during the first period of time and the second period of time may be a fixed voltage or a fixed current. The signal applied during the first period of time and the second period of time may also be a combination of multiple voltage or current. The voltage or the current may have positive value or negative value.
The signal applied during the first period of time and the second period of time may consist of positive voltage pulses, negative voltage pulses, zero voltage bias or a combination thereof. During the first period of time, the first counter electrode may be used for defined the reactions in which an electric current is expected to flow. And, during the second period of time, the second counter electrode may be used for defining the reactions in which an electric current is expected to flow. At least one measurement may be done after at least one pulse of the second signal applies during the second period of time.
The present invention presents a method of operation of a meter. To provide the meter with a properly working test strip for the duration of testing a sample, a first electrode of the test strip may initially be assigned to be a counter electrode and a second electrode may be assigned to be a counter electrode during later part of the duration of testing. Thus, the meter will be able to make sure that during later part of the duration of the testing operation is accurate. Furthermore, to let the meter enable identify the test strip, a plurality of resistor blocks may be formed on the working electrode. The plurality of resistor blocks may be coupled in series to each other. The total resistance of the plurality of resistor blocks may be identify the test strip before/after performing a test.
Another embodiment provides a method of utilizing a test strip to detect a diffusion factor of an intermediator in a sample, wherein the test strip includes a reaction region, and the reaction region includes a working electrode, a reference electrode, and a counter electrode. The method includes placing the sample in the reaction region; applying an first DC electrical signal to the working electrode during a first period; the mediator receiving electrons from or releasing electrons to the working electrode to generate an intermediator according to the first DC electrical signal; measuring a first current through the working electrode during the second period, wherein a polarity of the second DC electrical signal during the second period is inverse to the first DC electrical signal during the first period; and calculating the diffusion factor of the intermediator in the sample according to the first current. Wherein when applying a first DC electrical signal to the working electrode during a first period is applying the first electrode to be the counter electrode, the first counter electrode may be damaged during the first period time. When measuring the first current through the working electrode during the second period is applying the second electrode to be the counter electrode. Therefore, the current measurement may not be influenced by the damage of the first electrode.
Those skilled in the art will readily observe that numerous modifications and alterations of the device and method may be made while retaining the teachings of the invention. Accordingly, the above disclosure should be construed as limited only by the metes and bounds of the appended claims.
This application is a division of U.S. patent application Seer. No. 15/678,121, filed Aug. 16, 2017, and included herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15678121 | Aug 2017 | US |
| Child | 16591561 | US |
