Abstract
The invention refers to a device and a method of quantification of analytes concentration, making use of a device that comprises an electrochemical cell (1) which contains the analyte, a load (2) which is connected in parallel to the electrochemical cell (1), and a readout unit (3), which is connected in parallel with the load (2). This includes the stages of quantification of the concentration of analytes, the charge transfer from the electrochemical cell (1) to the load (2), the determination of the voltage across the load (2) and the determination of the analyte concentration from the correlation between the analyte concentration and the voltage across the load (2).
Claims
1. Device for the quantification of the concentration of analytes in a sample, that comprises: an electrochemical cell (1), which uses a volume of a sample containing an analyte, the concentration of which is to be determined, a load (2), composed of a combination of at least one capacitive load (4) and/or one resistive load (5), connected in parallel with the electrochemical cell (1), with such an equivalent resistance value that puts the electrochemical cell (1) to work under diffusion-limited conditions and that forces the electrochemical cell (1) to enter in a non-steady state in which the output voltage decreases with time, and continuous current is generated from the electrochemical cell (1), the current being transferred by the electrochemical cell (1) during a single discharge cycle totally or partially to a capacitive load (4) and in which the built-up voltage across the capacitive load (4) is an indicator of the analyte concentration in the electrochemical cell (1), and a reading element (3), connected in parallel to at least one of the capacitive (4) or resistive (5) loads composing the load (2), and which measures the voltage of such load (4,5) based on which the concentration of the analyte in the electrochemical cell (1) is determined.
2. The device according to claim 1, wherein the load (2) is predominantly a capacitive load (4) and the resistive contribution to the load (5) is set by the ohmic resistance of the electrodes of the electrochemical cell (1), the connecting tracks between the electrochemical cell (1) and the capacitive load (4) and the electrical connections of the assembly.
3. The device according to claim 1, wherein the capacitive load (4) is composed of a matrix of capacitors, which provides discretized information on the concentration of the analyte in the electrochemical cell (1) from the voltage reached in each of the capacitors.
4. The device according to claim 1, wherein the overall load (2) is composed of two parallel branches connected in parallel to the electrochemical cell (1), and where the first branch, featuring only a resistive element, is the predominant load that sets the electrochemical cell (1) in a diffusion-limited regime and where the second branch is composed of a resistive load (5), a capacitive load (4) and a diode connected in series, and where the operation of diode restricts the current flow in the second branch based on the capacitor and electrochemical cell (1) voltages and allows to hold the charge accumulated in the capacitive load (4).
5. The device of claim 4 wherein the value of the resistive load (5) in the second branch is at least five times the value of the predominant resistive load of the first branch.
6. The device according to claim 1, wherein the load (2) connected to the electrochemical cell (1) is predominantly resistive (5), being preferably a resistor, that sets the electrochemical cell (1) in diffusion-limited regime and where the elapsed time of the voltage decay of the electrochemical cell (1) between two different preset voltage values is measured using a readout unit (3).
7. The device according to claim 1, wherein the readout unit (3) comprises at least: a transistor (8) that is activated when the voltage on the load (2) reaches a threshold value, and an indicator (6), which emits a light, acoustic or vibrating signal when the transistor (8) starts conducting.
8. The device according to claim 1, wherein the readout unit (3) is powered by the energy generated by the electrochemical cell (1).
9. The device according to claim 1, wherein the readout unit (3) is powered by a power source external to the device.
10. The device according to claim 1, wherein the fuel in the electrochemical cell (1) is blood and the analyzed analyte is glucose.
11. The device according to claim 1, wherein the volume of sample containing the analyte to be quantified is in the order of 0.1-50 ul.
12. The device according to claim 1, wherein the sample containing the analyte to be quantified is flowing.
13. A method for the quantification of the concentration of analytes in a sample, which uses the device according to claim 1, and wherein it comprises the steps of: connecting the electrochemical cell (1), the load (2) and the reading element (3), working the electrochemical cell (1) under diffusion-limited conditions, transferring a continuous current in a single charging cycle from the electrochemical cell (1) to the load (2), determining the voltage at the load (2) by means of the reading element (3), and/or determining the time elapsed until a threshold voltage is reached in the electrochemical cell (1) by means of the readout unit (3), and determining the analyte concentration in the electrochemical cell (1).
14. The method of claim 13, wherein the load (2) is predominantly a capacitive load (4), and the analyte concentration is determined from the relationship that exists between the built-up voltage at the capacitive load (4) and the analyte concentration in the electrochemical cell (1).
15. The method of claim 13, wherein the load (2) comprises at least two parallel branches connected in parallel to the electrochemical cell (1), and in which a first branch comprises such a resistive element that forces the electrochemical cell (1) to work in a diffusion limited regime and in which a second branch comprises, connected in series, a resistive load (5), a capacitive load (4) and a diode, and the concentration of the analyte is determined from the relationship that exists between the built-up voltage of the capacitive load (4) and the concentration of the analyte in the electrochemical cell (1).
16. The method of claim 13, wherein the load (2) is a predominantly resistive load (5), and the analyte concentration is determined from the relationship between the time elapsed until a threshold voltage in the electrochemical cell (1) is reached and the analyte concentration in the electrochemical cell (1).
Description
DESCRIPTION OF THE DRAWINGS
[0053] In order to complete the description of the invention and improve the understanding of the invention characteristics, according to the preferred embodiment example, a set of drawing is presented as an integral unit of the invention description. This set of drawings, being illustrative and non-restrictive, represent the following:
[0054] FIG. 1.—Shows a block-wise schematic representation of the device that carries out the procedure of analyte concentration quantification that is the subject of this invention.
[0055] FIG. 2.—Shows a polarization curve of the electrochemical cell, when this is a fuel cell, a battery or a hybrid.
[0056] FIG. 3.—A) shows the scheme of the first embodiment for analyte quantification in an electrochemical cell, where the major load corresponds to a capacitive element. B) Shows a chart where the voltage evolution in the capacitive load versus time has been depicted. Three different built-up capacitor voltage patterns corresponding to three different analyte concentrations are displayed. C) Shows a calibration curve obtained when the built-up capacitor voltage versus analyte concentration at a particular time—computed from connection of electrochemical cell to a capacitor or a series of capacitors—is depicted.
[0057] FIG. 4.—Shows a scheme of the second methodology for analyte quantification in an electrochemical cell, where the major load corresponds to a resistive element.
[0058] FIG. 5.—A) Shows a scheme of the electrochemical cell, the load and the readout element in the case that the load corresponds to a resistive load. B) Shows the voltage evolution of the electrochemical cell versus time when the load connected to it is a resistive load for different analyte concentrations, being said time the time elapsed since the resistive load connection. C) Shows a calibration curve obtained when the time elapsed in the drop of the voltage of the electrochemical cell between two values is depicted at different analyte concentrations.
[0059] FIG. 6.—Shows an embodiment of the invention when the electrochemical cell is connected to a capacitive charge and an integrated readout element.
[0060] FIG. 7.—Shows the fuel cell voltage response when connected to a capacitor as a function of the capacitor size. For a constant concentration of analyte (7.5 mM glucose), and different capacitor sizes: C=1, 1.36, 2 and 3.3 mF.
[0061] FIG. 8.—Shows the fuel cell voltage response when connected to a capacitor as a function of the glucose concentration, for a constant capacitor size of 2 mF and for different glucose concentrations (6.2, 7.8 and 11.1 mM).
[0062] FIG. 9.—Shows the calibration curve obtained from the fuel cell voltage at a specific time (50 s) after the fuel cell has been connected to a capacitor (2 mF) versus the concentration of glucose in the sample.
[0063] FIG. 10.—Shows an embodiment of the invention in which the electrochemical cell is connected to a resistive load and an integrated readout element.
[0064] FIG. 11.—Shows the electrochemical cell voltage evolution with time for different analyte concentrations after being connected to a specific resistive load.
[0065] FIG. 12.—a) Shows the relationship between the times elapsed in the drop of the voltage of the electrochemical cell from open-circuit potential to a specific threshold voltage value for different analyte concentrations. b) Shows the influence of the resistor value on the elapsed times for electrochemical cell to reach a fixed threshold of 0.45 V from its open-circuit potential for various analyte concentrations.
[0066] FIG. 13.—a) Shows the built-up voltage across the capacitor C1 for different analyte concentrations, while the voltage across the electrochemical cell is majorly dropped due to the influence of R1. b) Calibration curve obtained between measured output capacitor voltage and the concentration of analyte.
[0067] FIG. 14.—(a, b) Shows the modulations of the output voltage levels for different analyte concentrations based on the choice of combinations of R1, R2 and C1
[0068] FIG. 15.—Shows the experimental results to modulate the level of stable output voltage across capacitor depending on the choice of resistor R2 for a given analyte concentration.
PREFERRED EMBODIMENT OF THE INVENTION
[0069] In the following, and supported by FIGS. 1 to 15, the preferred embodiment of the device and procedure for quantification of the concentration of analytes in an electrochemical cell are being described.
[0070] In a first embodiment, as depicted in FIG. 5, the device comprises an electrochemical cell (1) connected in parallel to a load (2)—which is a capacitor (4) in this case and a readout element (3). Once the circuit is closed, the electrical charge generated in the electrochemical cell is transferred to the capacitor (4). The built-up voltage in the capacitor VC (4) depends on the accumulated charge that has been transferred from the electrochemical cell (1) that at the same time depends on the analyte concentration. Said charge depends on the analyte concentration present in the sample of the electrochemical cell (1).
[0071] The readout element (3), as shown in FIG. 6, consists of a set of transistors (8) that are in open or close state depending on the capacitor voltage (4) with the aim of providing a digital result split in different levels of analyte concentration, previously stablished. The readout result is shown in several electrochromic displays (6,7), that will be turned on upon the enabling of the conducting state of the transistors (8), that is, when the capacitor voltage (4) exceeds a threshold value. In this particular configuration, the present embodiment is able to discriminate three different concentration levels of analyte.
[0072] FIG. 7 shows the fuel cell voltage evolution when connected to a capacitor C of values 1 mF, 1.36 mF, 2 mF and 3.3 mF, while operated with a 7.5 mM of glucose concentration. Capacitance values allow tuning the fuel cell (1) output voltage.
[0073] FIG. 8 shows the experimental electrochemical cell (1) voltage values (V.sub.S) with time for different concentrations of glucose (6.2 mM, 7.8 mM and 11.1 mM) when capacitor is set to 2 mF. As shown in the figure, the electrochemical cell (1) voltage value is correlated with the concentration of glucose and therefore, by measuring the electrochemical cell (1) voltage at a specific time, the concentration of analyte can be determined.
[0074] FIG. 9 shows the calibration curve of V.sub.out, which is the capacitor voltage (V.sub.C(t)) once the electrochemical cell (1) has been depleted versus the glucose concentration.
[0075] The readout unit (3) shown in FIG. 6, consists on a set of transistors (8) that are in open or close state depending on the capacitor (4) voltage (V.sub.C(t)) with the aim of providing a digital result split in different levels of analyte concentration. The readout result is shown in several electrochromic displays (6, 7), that will be turned on upon the enabling of the conducting state of the transistors (8), that is, when the capacitor (4) voltage (V.sub.C(t)) exceeds a threshold value. In this particular configuration, the present embodiment is able to discriminate three different concentration levels of analyte.
[0076] In another embodiment, as depicted in FIG. 10, an electrochemical cell (1) is connected in parallel to a load (2)—which in this case is a resistor (5)—and to a readout element (3). The readout element (3) consists of two blocks: a first block (9) that measures the voltage drop at the resistor (5) and detects the threshold voltage values that determine the start and the end points of time monitoring. A second block (10) is used to quantify said time. In this particular case, time is measured by means of an RC circuit, where the electrical current is limited by the resistor and the built-up voltage in the capacitor (4) allows to derive information about the time that the RC circuit has been connected to the electrochemical cell (1).
[0077] The built-up voltage of the capacitor in the RC circuit in block (10) depends on the elapsed time in which the voltage of the electrochemical cell (1) evolves from an initial value to a final value. This interval is determined by block (9).
[0078] The magnitude of the interval depends on the analyte concentration in the electrochemical cell (1). Therefore, by measuring the built-up voltage in the capacitor of block (10) once the voltage in the electrochemical cell (1) has reached a threshold value, the analyte concentration can be quantified. Higher analyte concentrations originate higher built-up voltages in the capacitor, as it will have been charged for a larger period of time.
[0079] In another embodiment as shown in FIG. 11, the electrochemical cell (1) is connected to a resistive load. The potential across the electrochemical cell dropped from its open-circuit potential at different rates depending on the analyte concentration for a given resistor value. It can be observed that the decay rate is faster in case of smaller analyte concentrations.
[0080] As it also can be seen from FIG. 11, the drop in these voltages are affected by the value of load resistor used. The rate of the decay in voltage is higher for a greater load value. In this embodiment, the time elapsed for the voltage of electrochemical cell (1) to drop from the open-circuit potential to a specific threshold level (mentioned in legends) when subjected to only a resistive load is presented in FIG. 12(a). For a particular resistor value of 10 kΩ, a proportional increase in elapsed time is observed with increase in analyte concentrations for different threshold voltage levels. FIG. 12(b) shows the elapsed time for the electrochemical cell to reach 0.45 V threshold value from its open-circuit potential when subjected to only a resistive load is shown. It is observed that the slope of the linear fitted curves increased with the increase in load resistor value.
[0081] In another embodiment, the electrochemical cell (1) has been connected to the circuit shown in FIG. 3 with R1=10 KOhms, R2=100 KOhms and C1=47 μF. The electrochemical cell (1) voltage dropped in value due to the major influence of resistor R1. The output voltage in the capacitor builds up during this process until the diode D1 interrupts passage of significant current.
[0082] As shown in FIG. 13, the experimental results indicated different values of output voltage across capacitor for different analyte concentrations. The output voltage maintains a stable value for at least 30 s due to the presence of diode that restricts the immediate discharge of the capacitor.
[0083] In additional embodiments, the electrochemical cell (1) has been connected to the circuit shown in FIG. 3 with R1=10 KOhms and C1=47 μF, and the output voltage levels across the capacitor C1 have been modulated by setting R2 to different values (100 and 220 KOhms) without affecting the pattern of response for different analytes as shown in FIG. 14. The effect of R2 value on the capacitor built-up voltage has been also measured by setting 5 mM analyte concentration and R2 values of 57KΩ, 100 KΩ and 220 KΩ, as shown in FIG. 15.
