CN112731254B - Method, device, system and equipment for determining calibration parameters of current measurement circuit - Google Patents
Method, device, system and equipment for determining calibration parameters of current measurement circuit Download PDFInfo
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- CN112731254B CN112731254B CN202110344178.8A CN202110344178A CN112731254B CN 112731254 B CN112731254 B CN 112731254B CN 202110344178 A CN202110344178 A CN 202110344178A CN 112731254 B CN112731254 B CN 112731254B
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- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R35/00—Testing or calibrating of apparatus covered by the other groups of this subclass
- G01R35/005—Calibrating; Standards or reference devices, e.g. voltage or resistance standards, "golden" references
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
Abstract
The application discloses a method, a device, a system and equipment for determining calibration parameters of a current measurement circuit. The method for determining the calibration parameter of the current measurement circuit comprises the following steps: acquiring the output current of any one capacitor on a capacitor plate, wherein the capacitors correspond to current measurement channels of nanopores of a nanopore gene sequencer one by one, the capacitor plate comprises L capacitors, and L is a positive integer; and determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measurement circuit and the output current. By adopting the method for determining the calibration parameters of the current measurement circuit, the accuracy of gain and offset error measurement can be improved, and the accuracy of the calibration result of the current measurement circuit is improved.
Description
Technical Field
The application relates to the technical field of sequencing, in particular to a method, a device, a system and equipment for determining calibration parameters of a current measurement circuit.
Background
A nanopore gene sequencer serves as a device capable of rapidly and accurately measuring a gene sequence. In measuring the gene sequence, the output current of each nanopore of the biochip may be measured, and the gene sequence may be measured based on the output current of each nanopore.
Since the output current of each nanopore of the biochip is measured, there may be a measurement deviation. Therefore, the measured output current of each nanopore needs to be calibrated. At present, the biochip is usually replaced by a resistance plate, and the gain and offset error of the current corresponding to each resistance is calculated by measuring the output current of each resistance on the resistance plate, so as to calibrate the measured output current of each nanopore based on the gain and offset error of the current corresponding to each resistance.
However, because of the small current range measured by nanopore gene sequencers, the resistors on the resistive plate are typically large-value resistors. The precision of the large-resistance resistor is generally low, and the resistor generates thermal noise, so that the accuracy of the calculated gain and offset errors is low, and the accuracy of the calibration result of the output current is low.
Disclosure of Invention
An object of the embodiments of the present application is to provide a method, an apparatus, a system, and a device for determining a calibration parameter of a current measurement circuit, so as to solve the technical problems in the prior art that accuracy of gain and offset errors is low, and accuracy of a calibration result of an output current is low.
The technical scheme of the application is as follows:
in a first aspect, a method for determining a calibration parameter of a current measurement circuit is provided, which may include:
acquiring the output current of any one capacitor on a capacitor plate, wherein the capacitors correspond to current measurement channels of nanopores of a nanopore gene sequencer one by one, the capacitor plate comprises L capacitors, and L is a positive integer;
and determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measurement circuit and the output current.
In some embodiments, before obtaining the output current of any one of the capacitors on the capacitor plate, the method may further include:
measuring N output currents corresponding to L capacitors of a capacitor plate respectively, and storing the N output currents corresponding to the L capacitors respectively, wherein N is a positive integer;
obtaining an output current of any one of the capacitors on the capacitor plate, comprising:
m output current sequences of any capacitor on the capacitor plate are obtained from N output currents corresponding to L capacitors of the capacitor plate, wherein M is a positive integer.
In some embodiments, determining a gain and offset error of a current measurement channel of a nanopore corresponding to a capacitance based on a signal characteristic of an excitation signal of a current measurement circuit and an output current may include:
processing M output current sequences of any capacitor on the capacitor plate to obtain amplitudes and direct current components corresponding to the M output current sequences respectively, and obtaining M amplitudes and M direct current components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct-current components and the signal characteristics.
In some embodiments, the signal characteristic of the excitation signal may include a slope of the excitation signal;
calculating gain and offset errors of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct current components, and the signal characteristics, may include:
calculating the measurement capacitance values corresponding to the M output currents of the capacitor based on the M amplitude values and the slope of the excitation signal;
calculating an average measured value of the capacitor based on the measured capacitance values corresponding to the M output currents of the capacitor;
calculating an average direct current component of the capacitor based on the M direct current components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average measurement value of the capacitor and the average direct current component of the capacitor.
In some embodiments, calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitance based on the average measured value of the capacitance, the average dc component of the capacitance, may include:
calculating the gain of the current measurement channel of the nanopore corresponding to the capacitor based on the real value and the average measured value of the capacitor;
and calculating the offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average direct current component of the capacitor.
In some embodiments, the capacitor may be a picofarf capacitor.
In some embodiments, the excitation signal may be any one of a triangular wave and a sinusoidal wave.
In some embodiments, obtaining the output current of any one of the capacitors on the capacitor plate may include:
the output current of any one capacitor on the capacitor plate is obtained through the analog-digital converter ADC.
In a second aspect, there is provided a system for determining a calibration parameter of a current measurement circuit, the system may comprise:
the capacitance plate can comprise L capacitors, the capacitors correspond to current measurement channels of the nanopore gene sequencer one by one, and L is a positive integer;
the signal processing and converting module can be connected with the capacitor plate and is used for collecting the output current of each capacitor on the capacitor plate;
a controller connectable to the signal processing and conversion module for performing the method of determining a calibration parameter of a current measurement circuit as shown in any one of the embodiments of the first aspect;
and the power supply module can be used for providing working voltage for the capacitor plate, the signal processing and converting module and the controller.
In a third aspect, there is provided an apparatus for determining a calibration parameter of a current measurement circuit, the apparatus may include:
the acquisition module can be used for acquiring the output current of any capacitor on a capacitor plate, the capacitors correspond to current measurement channels of a nanopore gene sequencer one by one, the capacitor plate comprises L capacitors, and L is a positive integer;
and the determining module can be used for determining the gain and offset error of the current measuring channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measuring circuit and the output current.
In a fourth aspect, an electronic device is provided, which may include:
a processor;
and a memory storing programs or instructions;
wherein the processor, when reading and executing the program or instructions, implements a method of determining a current measurement circuit calibration parameter as shown in any embodiment of the first aspect.
In a fifth aspect, there is provided a readable storage medium having stored thereon a program or instructions, which when executed by a processor, implements the method for determining a calibration parameter of a current measurement circuit as shown in any one of the embodiments of the first aspect.
The technical scheme provided by the embodiment of the application at least has the following beneficial effects:
according to the embodiment of the application, the gain and offset errors of the current measurement channels of the nanopore corresponding to the capacitor are calculated based on the acquired output current of the capacitor and the signal characteristics of the excitation signal of the current measurement circuit, wherein the capacitor and the current measurement channels of the nanopore gene sequencer are in one-to-one correspondence. Therefore, the gain and offset errors of the current measurement channel of the nanopore gene sequencer can be determined based on the capacitance in one-to-one correspondence with the current measurement channel of the nanopore gene sequencer, and compared with the gain and offset errors of the current measurement channel of the nanopore gene sequencer determined based on a resistance plate in the prior art, on one hand, the accuracy of the capacitance is easier to control, and the capacitance does not generate thermal noise, so that the accuracy of the gain and offset errors can be effectively improved, and the accuracy of a calibration result can be effectively improved.
On the other hand, because the capacitor is adopted in the embodiment of the application, the excitation signal is correspondingly an alternating current signal, and compared with the prior art that the resistance plate is driven by a direct current signal, the alternating current signal is insensitive to the direct current voltage bias of the circuit, and the frequency of the excitation signal is adjustable and known, so that interference signals of other frequency bands are easily filtered, and thus, the accuracy of gain and offset errors can be further improved, and the accuracy of a calibration result is improved.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the application.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the application and are not to be construed as limiting the application.
FIG. 1 is a schematic diagram of a current measurement circuit of a nanopore gene sequencer according to the prior art;
FIG. 2 is a schematic structural diagram of a system for determining a calibration parameter of a current measurement circuit according to an embodiment of the present disclosure;
fig. 3 is a schematic flowchart of a method for determining a calibration parameter of a current measurement circuit according to an embodiment of the present disclosure;
fig. 4 is a schematic structural diagram of an apparatus for determining a calibration parameter of a current measurement circuit according to an embodiment of the present disclosure;
fig. 5 is a schematic structural diagram of an electronic device according to an embodiment of the present application.
Detailed Description
In order to make the technical solutions of the present application better understood by those of ordinary skill in the art, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings.
It should be noted that the terms "first," "second," and the like in the description and claims of this application and in the drawings described above are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in sequences other than those illustrated or described herein. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.
Based on the background art, in the prior art, the accuracy of the calculated gain and offset errors is low and the accuracy of the calibration result of the output current is low due to the fact that the precision of the large-resistance resistor is generally low and the resistor generates thermal noise.
As shown in fig. 1, the current measuring circuit of the nanopore gene sequencer in the prior art includes a biochip 110, a signal processing and converting module 120, a power supply module 130, and a controller 140.
The biochip 110 is mainly composed of a nanopore array, all nanopores share a common electrode, each nanopore is provided with a working electrode, the common electrode is grounded, and the working electrode is connected to the input voltage of the power module 130. An analog channel (i.e., a current measurement channel) is disposed between the signal processing and converting module 120 and each nanopore of the biochip 110, and the signal processing and converting module 120 can measure the output current of each nanopore through the analog channel corresponding to each nanopore, and can perform amplification processing and analog-to-digital conversion processing on the measured output current to obtain an amplified digital signal. The power module 130 may provide an operating voltage to each nanopore of the biochip 110, the signal processing and converting module 120, and the controller 140, and serves to generate an excitation signal (voltage on the working electrode). The controller 140 may control the signal processing and converting module 120 to measure the output current of each nanopore through the digital bus, and may calculate the gain and offset error of the current corresponding to each resistor, where the calculated gain and offset error may be used to calibrate the output current of the nanopore measured during the operation of the nanopore gene sequencer.
Since the signal processing and converting module 120 may have measurement deviation, it is necessary to calculate the gain and offset error of the analog channel corresponding to each nanopore of the current measuring circuit before the nanopore gene sequencer leaves the factory or works, so as to calibrate the measurement of the current measuring circuit. Specifically, the conventional method for calculating the gain and offset errors of the current measuring circuit is to externally connect a resistance plate provided with a plurality of high-precision resistors, replace the biochip 110 with the resistance plate, correspond each high-precision resistor on the resistance plate to a nanopore, and calculate the gain and offset errors of the current measuring circuit by using a two-point calibration method. The method comprises the following specific steps: first, each resistor on the resistor plate is used to simulate each nanopore on the biochip, two different operating voltages (corresponding to zero calibration and span calibration) are applied, and then the output current of each resistor at the two different operating voltages is read. And then, calculating the gain and offset error of each analog channel, namely the gain and offset error of the current measurement channel corresponding to each nanopore, according to the sampled output current of each resistor under two different working voltages.
Since the current measuring circuit of the nanopore gene sequencer usually has a small current range, the high-precision resistance on the resistance plate needs to be a resistance of G Ω magnitude. However, such a large-resistance resistor is generally difficult to achieve high precision, and it is difficult to eliminate voltage offset of the circuit itself, thermal noise generated by the resistor, and electromagnetic interference in the environment, which may affect the accuracy of the output current of each resistor, and thus may affect the accuracy of the calculated gain and offset error, resulting in low accuracy of the calibration result of the output current.
Based on the above findings, embodiments of the present application provide a method, an apparatus, a system, and a device for determining a calibration parameter of a current measurement circuit, which can calculate a gain and an offset error of a current measurement channel of a nanopore corresponding to a capacitor based on an obtained output current of the capacitor and a signal characteristic of an excitation signal of the current measurement circuit, where the capacitor and the current measurement channel of the nanopore of a nanopore gene sequencer are in one-to-one correspondence. Therefore, the gain and offset errors of the current measurement channel of the nanopore gene sequencer can be determined based on the capacitance in one-to-one correspondence with the current measurement channel of the nanopore gene sequencer, and compared with the gain and offset errors of the current measurement channel of the nanopore gene sequencer determined based on a resistance plate in the prior art, on one hand, the accuracy of the capacitance is easier to control, and the capacitance does not generate thermal noise, so that the accuracy of the gain and offset errors can be effectively improved, and the accuracy of a calibration result can be effectively improved.
On the other hand, because the capacitor is adopted in the embodiment of the application, the excitation signal is correspondingly an alternating current signal, and compared with the prior art that the resistance plate is driven by a direct current signal, the alternating current signal is insensitive to the direct current voltage bias of the circuit, and the frequency of the excitation signal is adjustable and known, so that interference signals of other frequency bands are easily filtered, and thus, the accuracy of gain and offset errors can be further improved, and the accuracy of a calibration result is improved.
The following describes a method, an apparatus, a system, and a device for determining a calibration parameter of a current measurement circuit according to an embodiment of the present application with reference to the accompanying drawings.
Fig. 2 is a schematic structural diagram illustrating a system for determining a calibration parameter of a current measurement circuit according to an embodiment of the present application, where as shown in fig. 2, the system for determining a calibration parameter of a current measurement circuit may include:
the capacitor plate 210, the capacitor plate 210 may include L capacitors, the capacitors correspond to current measurement channels of the nanopore gene sequencer one-to-one, and L is a positive integer;
the signal processing and converting module 220 may be connected to the capacitor plate 210, and may be configured to collect an output current of each capacitor on the capacitor plate 210;
a controller 240, which may be connected to the signal processing and converting module 220, and may be configured to perform the method for determining the calibration parameter of the current measuring circuit shown in fig. 3;
the power module 230 may be configured to provide an operating voltage for the capacitor plate 210, the signal processing and converting module 220, and the controller 240.
It is understood that there may be an analog channel, i.e. a current measurement channel, between the signal processing and converting module 220 and each capacitor of the capacitor plate 210, so that the signal processing and converting module 220 may measure the output current of each capacitor through the current measurement channel corresponding to each capacitor of the capacitor plate 210. All capacitors of the capacitor plate 210 may share a common electrode, and each capacitor may have a working electrode, the common electrode is grounded, and the working electrode is connected to the input voltage of the power module 230.
The controller 240 of the system for determining calibration parameters of a current measurement circuit described above implements the specific implementation principle and technical effect of the method for determining calibration parameters of a current measurement circuit shown in fig. 3, which will be described in the method for determining calibration parameters of a current measurement circuit shown in fig. 3, and for the sake of brevity, will not be described herein again.
The following describes a method for determining a calibration parameter of a current measurement circuit provided in an embodiment of the present application.
Fig. 3 is a schematic flowchart illustrating a method for determining a calibration parameter of a current measurement circuit according to an embodiment of the present application, where as shown in fig. 3, the method may include the following steps:
and S310, acquiring the output current of any capacitor on the capacitor plate.
The capacitance plate can comprise L capacitors, the capacitors on the capacitance plate correspond to current measurement channels of the nanopores of the nanopore gene sequencer one to one, and L is a positive integer. That is, the number of capacitors of the capacitor plate is the same as the number of nanopores of the nanopore gene sequencer, and the capacitors and the nanopores are in one-to-one correspondence, that is, when the calibration parameters of the current measuring circuit are determined, the capacitor plate is used for replacing the biochip, and each capacitor on the capacitor plate is used for replacing the corresponding nanopore.
The capacitance on the capacitor plate can be a picofarad pF capacitor.
As an example, when determining calibration parameters of a current measurement circuit, i.e., determining gain and offset errors of a current measurement circuit of a nanopore gene sequencer, the output current of any one of the capacitors on the capacitor plate may be obtained first.
It will be appreciated that each capacitance on the capacitive plate can be determined to be any one of the capacitances described above, and thus, the output current of each capacitance on the capacitive plate can be obtained.
And S320, determining the gain and offset error of the current measuring channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measuring circuit and the output current.
The excitation signal may be any one of a triangular wave and a sine wave, or may be another alternating current signal as long as the frequency and the slope thereof are known.
As an example, after the output current of any one of the capacitors on the capacitive plate is acquired, the signal characteristic of the excitation signal of the current measurement circuit may be acquired. And then, determining the gain and offset error of the current measurement channel of the nanopore corresponding to any capacitor based on the signal characteristic of the excitation signal of the current measurement circuit and the obtained output current of any capacitor on the capacitor plate, wherein the gain and offset error is the calibration parameter of the current measurement circuit. The gain and offset errors may be stored in a non-volatile memory (NVM), such as an EEPROM (Electrically Erasable Programmable read only memory), as calibration parameters for the current measurement circuit for calibrating the measured output current of the nanopore during operation of the nanopore gene sequencer.
It can be understood that the gain and offset error of the current measurement channel of the nanopore corresponding to each capacitor on the capacitor plate can be calculated according to the method described above, so as to calibrate the measured output current of each nanopore based on the gain and offset error of the current measurement channel of the nanopore corresponding to each capacitor during the operation of the nanopore gene sequencer. The method for determining the calibration parameters of the current measurement circuit provided by the embodiment of the application can also be applied to other current measurement circuits, especially weak current measurement circuits.
According to the embodiment of the application, the gain and offset errors of the current measurement channels of the nanopore corresponding to the capacitor are calculated based on the acquired output current of the capacitor and the signal characteristics of the excitation signal of the current measurement circuit, wherein the capacitor and the current measurement channels of the nanopore gene sequencer are in one-to-one correspondence. Therefore, the gain and offset errors of the current measurement channel of the nanopore gene sequencer can be determined based on the capacitance in one-to-one correspondence with the current measurement channel of the nanopore gene sequencer, and compared with the gain and offset errors of the current measurement channel of the nanopore gene sequencer determined based on a resistance plate in the prior art, on one hand, the accuracy of the capacitance is easier to control, and the capacitance does not generate thermal noise, so that the accuracy of the gain and offset errors can be effectively improved, and the accuracy of a calibration result can be effectively improved.
On the other hand, because the capacitor is adopted in the embodiment of the application, the excitation signal is correspondingly an alternating current signal, and compared with the prior art that the resistance plate is driven by a direct current signal, the alternating current signal is insensitive to the direct current voltage bias of the circuit, and the frequency of the excitation signal is adjustable and known, so that interference signals of other frequency bands are easily filtered, and thus, the accuracy of gain and offset errors can be further improved, and the accuracy of a calibration result is improved.
Moreover, because the pF stage capacitor is easier to manufacture and controllable in precision, the accuracy of gain and offset errors can be further improved.
In some embodiments, M output currents of the capacitor may be obtained, and accordingly, before the step S310, the following steps may be further included:
and measuring N output currents corresponding to the L capacitors of the capacitor plate respectively, and storing the N output currents corresponding to the L capacitors respectively.
Wherein, N is a positive integer, and the value of N can be set according to actual conditions.
At this time, the specific implementation manner of the step S310 may be as follows:
m output current sequences of any capacitor on the capacitor plate are obtained from N output currents corresponding to L capacitors of the capacitor plate.
Where M is a positive integer and M is less than or equal to N, the value of M may be set according to practical situations, and each output current sequence may include a plurality of output currents, such as an integer power of 2, for example 1024, 2048, 4096, and the like.
As an example, before obtaining the output current of any one capacitor on the capacitor plate, N output currents corresponding to L capacitors of the capacitor plate may be measured, that is, N output currents corresponding to each capacitor on the capacitor plate are obtained through measurement. And determining N output currents corresponding to any one capacitor on the capacitor plate from the N output currents corresponding to the L capacitors of the capacitor plate, and acquiring M output current sequences of any one capacitor on the capacitor plate from the N output currents corresponding to the capacitor. And then, based on the obtained M output current sequences of any one capacitor on the capacitor plate and the signal characteristics of the excitation signal of the current measurement circuit, determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor.
Therefore, M output current sequences of the capacitor are obtained, and a sufficient data basis can be provided for determining the gain and offset errors of the current measurement channel of the nanopore corresponding to the capacitor, so that the accuracy of the gain and offset errors can be further improved, and the accuracy of a calibration result can be further improved.
In some embodiments, the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor may be calculated based on the amplitude and the dc component corresponding to each of the M output current sequences of the capacitor, and accordingly, the specific implementation manner of the step S320 may be as follows:
processing M output current sequences of any capacitor on the capacitor plate to obtain amplitudes and direct current components corresponding to the M output current sequences respectively, and obtaining M amplitudes and M direct current components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct-current components and the signal characteristics.
As an example, when determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the signal characteristic and the output current of the excitation signal of the current measurement circuit, the M output current sequences of any one capacitor on the capacitor plate may be processed first, for example, Fast Fourier Transform (FFT) may be performed on each output current sequence in the M output current sequences of any one capacitor on the capacitor plate, so as to obtain the amplitude and the dc component corresponding to each output current sequence in the M output current sequences of the excitation signal with the frequency F, that is, the M amplitude and the M dc component. And calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct current components and the signal characteristics of the excitation signal of the current measurement circuit.
Therefore, on the basis of signal characteristics, the gain and offset errors of the current measurement channel of the nanopore corresponding to the capacitor are calculated by combining the amplitude and the direct current component corresponding to the M output current sequences of the capacitor, and the accuracy of the gain and offset errors can be further improved.
In some embodiments, the signal characteristic of the excitation signal may include a slope of the excitation signal. Correspondingly, at this time, the specific implementation manner for calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct-current components, and the signal characteristics may be as follows:
calculating the measurement capacitance values corresponding to the M output current sequences of the capacitor based on the M amplitude values and the slope of the excitation signal;
calculating an average measured value of the capacitor based on the measured capacitance values corresponding to the M output current sequences of the capacitor;
calculating an average direct current component of the capacitor based on the M direct current components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average measurement value of the capacitor and the average direct current component of the capacitor.
As an example, when calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct current components, and the signal characteristics, the capacitance value corresponding to each of the M output current sequences of the capacitor, i.e., the measurement capacitance value, may be calculated based on the M amplitudes and the slopes of the excitation signal. When the excitation signal is a triangular wave, the measured capacitance value corresponding to any output current sequence of the capacitor can be calculated according to the following formula (1):
wherein the content of the first and second substances,
a measured capacitance value representing a capacitance is measured,
representing the corresponding amplitude of the output current sequence and K representing the slope of the excitation signal.
After calculating the measured capacitance values corresponding to the M output current sequences of the capacitor, the method may be based on the measurements corresponding to the M output current sequences of the capacitorCapacitance value, calculating an average measure of capacitance
. Calculating the average DC component of the capacitor based on the DC components corresponding to the M output current sequences, i.e. M DC componentsDC. And calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average measurement value of the capacitor and the average direct current component of the capacitor.
Therefore, the gain and offset errors of the current measuring channels of the nano holes corresponding to the capacitors are calculated based on the average measured value of the capacitors and the average direct current component of the capacitors, so that the calculated gain and offset errors can better accord with the actual measurement deviation of the current measuring channels of the nano holes corresponding to the capacitors, and the accuracy of the gain and offset errors can be further improved.
In some embodiments, the specific implementation of calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average measured value of the capacitor and the average dc component of the capacitor may be as follows:
calculating the gain of the current measurement channel of the nanopore corresponding to the capacitor based on the real value and the average measured value of the capacitor;
and calculating the offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average direct current component of the capacitor.
When the excitation signal is a triangular wave, the gain of the current measurement channel of the nanopore corresponding to the capacitance can be calculated according to the following formula (2):
wherein the content of the first and second substances,
representing the gain of the current measurement channel of the nanopore corresponding to the capacitance,
represents an average measurement of the capacitance that is,
representing the true value of the capacitance.
And calculating the offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average direct current component of the capacitor. When the excitation signal is a triangular wave, the offset error of the current measurement channel of the nanopore corresponding to the capacitance can be calculated according to the following formula (3):
wherein the content of the first and second substances,
indicating the offset error of the nanopore current measurement channel corresponding to the capacitance,DCthe average dc component of the nanopore current measurement channel corresponding to the capacitance is represented. Namely, the average direct current component of the nanopore current measurement channel corresponding to the capacitor is the offset error of the nanopore current measurement channel corresponding to the capacitor.
It will be appreciated that when the excitation signal is a sinusoidal signal, equations (1) - (3) above also need to be adjusted accordingly.
Therefore, the gain of the current measuring channel of the nanopore corresponding to the capacitor is calculated based on the real value and the average measured value of the capacitor, and the offset error of the current measuring channel of the nanopore corresponding to the capacitor is calculated based on the average direct current component of the capacitor, so that the calculated gain and offset error can better accord with the actual measurement deviation of the current measuring channel of the nanopore corresponding to the capacitor, and the accuracy of the gain and offset error can be further improved.
In some embodiments, the specific implementation manner of obtaining the output current of any one capacitor on the capacitor plate may be as follows:
the output current of any one capacitor on the capacitor plate is obtained through the analog-digital converter ADC.
As an example, since the signal generated by the capacitor is usually an Analog signal, and the Analog signal is not convenient for data analysis and processing, when the output current of any one of the capacitors on the capacitor board is obtained, the output current of any one of the capacitors on the capacitor board can be obtained through an Analog-to-Digital Converter (ADC), so as to convert the output current of the capacitor from the Analog signal to a Digital signal. Therefore, a data base which is more convenient for analysis and calculation can be provided for the gain and offset errors of the current measuring channel of the nanopore corresponding to the capacitance in the subsequent determination.
Based on the same inventive concept, the application also provides a device for determining the calibration parameter of the current measurement circuit.
Fig. 4 is a schematic structural diagram of an apparatus for determining a calibration parameter of a current measurement circuit according to an embodiment of the present disclosure, and as shown in fig. 4, the apparatus 400 for determining a calibration parameter of a current measurement circuit may include:
the obtaining module 410 may be configured to obtain an output current of any one capacitor on a capacitor plate, where the capacitor corresponds to a current measurement channel of a nanopore gene sequencer one to one, the capacitor plate includes L capacitors, and L is a positive integer;
the determining module 420 may be configured to determine a gain and an offset error of the current measurement channel of the nanopore corresponding to the capacitance based on the signal characteristic of the excitation signal of the current measurement circuit and the output current.
In some embodiments, the apparatus 400 for determining a calibration parameter of a current measurement circuit may further include:
the measurement storage module can be used for measuring N output currents corresponding to L capacitors of the capacitor plate respectively and storing the N output currents corresponding to the L capacitors, wherein N is a positive integer;
the obtaining module 410 may be specifically configured to:
m output current sequences of any capacitor on the capacitor plate are obtained from N output currents corresponding to L capacitors of the capacitor plate, wherein M is a positive integer.
In some embodiments, the determining module 420 may include:
the processing unit can be used for processing the M output current sequences of any capacitor on the capacitor plate to obtain the amplitudes and the direct current components corresponding to the M output current sequences respectively and obtain the M amplitudes and the M direct current components;
and the computing unit can be used for computing the gain and offset error of the current measuring channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct-current components and the signal characteristics.
In some embodiments, the signal characteristic of the excitation signal comprises a slope of the excitation signal;
a computing unit, which may include:
the first calculating subunit is configured to calculate, based on the M amplitudes and the slopes of the excitation signals, measurement capacitance values corresponding to the M output current sequences of the capacitor, respectively;
the second calculating subunit may be configured to calculate an average measured value of the capacitor based on the measured capacitance values corresponding to the M output current sequences of the capacitor, respectively;
a third calculation subunit operable to calculate an average dc component of the capacitance based on the M dc components;
and the fourth calculating subunit is used for calculating the gain and the offset error of the current measuring channel of the nanopore corresponding to the capacitor based on the average measured value of the capacitor and the average direct current component of the capacitor.
In some embodiments, the fourth calculating subunit may include:
the first calculation component can be used for calculating the gain of the current measurement channel of the nanopore corresponding to the capacitor based on the real value and the average measured value of the capacitor;
and the second calculation component can be used for calculating the offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average direct current component of the capacitor.
In some embodiments, the capacitor may be a picofarf capacitor.
In some embodiments, the excitation signal may be any one of a triangular wave and a sine wave.
In some embodiments, the obtaining module 410 may be specifically configured to:
the output current of any one capacitor on the capacitor plate is obtained through the analog-digital converter ADC.
The device for determining the calibration parameter of the current measurement circuit provided in the embodiment of the present application can be used to implement the methods provided in the above method embodiments, and the implementation principles and technical effects are similar, and for brevity, no further description is given here.
Based on the same inventive concept, the embodiment of the application also provides the electronic equipment.
Fig. 5 is a schematic structural diagram of an electronic device according to an embodiment of the present application. As shown in fig. 5, the electronic device may include a processor 501 and a memory 502 storing computer programs or instructions.
Specifically, the processor 501 may include a Central Processing Unit (CPU), or an Application Specific Integrated Circuit (ASIC), or may be configured as one or more Integrated circuits implementing embodiments of the present invention.
The processor 501 reads and executes computer program instructions stored in the memory 502 to implement the method for determining the calibration parameter of the current measurement circuit in any of the above embodiments.
In one example, the electronic device can also include a communication interface 503 and a bus 510. As shown in fig. 5, the processor 501, the memory 502, and the communication interface 503 are connected via a bus 510 to complete communication therebetween.
The communication interface 503 is mainly used for implementing communication between modules, devices, units and/or devices in the embodiments of the present invention.
The electronic device may execute the method for determining the calibration parameter of the current measurement circuit in the embodiment of the present invention, so as to implement the method and apparatus for determining the calibration parameter of the current measurement circuit described in fig. 1 to 4.
In addition, in combination with the method for determining the calibration parameter of the current measurement circuit in the above embodiments, the embodiments of the present invention may be implemented by providing a readable storage medium. The readable storage medium having stored thereon program instructions; the program instructions, when executed by a processor, implement a method of determining a calibration parameter for a current measurement circuit as in any of the above embodiments.
It is to be understood that the invention is not limited to the specific arrangements and instrumentality described above and shown in the drawings. A detailed description of known methods is omitted herein for the sake of brevity. In the above embodiments, several specific steps are described and shown as examples. However, the method processes of the present invention are not limited to the specific steps described and illustrated, and those skilled in the art can make various changes, modifications and additions or change the order between the steps after comprehending the spirit of the present invention.
The functional blocks shown in the above-described structural block diagrams may be implemented as hardware, software, firmware, or a combination thereof. When implemented in hardware, it may be, for example, an electronic circuit, an Application Specific Integrated Circuit (ASIC), suitable firmware, plug-in, function card, or the like. When implemented in software, the elements of the invention are the programs or code segments used to perform the required tasks. The program or code segments may be stored in a machine-readable medium or transmitted by a data signal carried in a carrier wave over a transmission medium or a communication link. A "machine-readable medium" may include any medium that can store or transfer information. Examples of a machine-readable medium include electronic circuits, semiconductor memory devices, ROM, flash memory, Erasable ROM (EROM), floppy disks, CD-ROMs, optical disks, hard disks, fiber optic media, Radio Frequency (RF) links, and so forth. The code segments may be downloaded via computer networks such as the internet, intranet, etc.
It should also be noted that the exemplary embodiments mentioned in this patent describe some methods or systems based on a series of steps or devices. However, the present invention is not limited to the order of the above-described steps, that is, the steps may be performed in the order mentioned in the embodiments, may be performed in an order different from the order in the embodiments, or may be performed simultaneously.
As described above, only the specific embodiments of the present invention are provided, and it can be clearly understood by those skilled in the art that, for convenience and brevity of description, the specific working processes of the system, the module and the unit described above may refer to the corresponding processes in the foregoing method embodiments, and are not described herein again. It should be understood that the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive various equivalent modifications or substitutions within the technical scope of the present invention, and these modifications or substitutions should be covered within the scope of the present invention.
Claims (12)
1. A method for determining a calibration parameter for a current measurement circuit, comprising:
acquiring the output current of any one capacitor on a capacitor plate, wherein the capacitors correspond to current measurement channels of nanopores of a nanopore gene sequencer one by one, the capacitor plate comprises L capacitors, and L is a positive integer;
and determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measurement circuit and the output current.
2. The method of claim 1, further comprising, prior to said obtaining the output current of any one of the capacitors on the capacitive plate:
measuring N output currents corresponding to L capacitors of the capacitor plate respectively, and storing the N output currents corresponding to the L capacitors respectively, wherein N is a positive integer;
the obtaining of the output current of any one capacitor on the capacitor plate includes:
obtaining M output current sequences of any capacitor on the capacitor plate from N output currents corresponding to L capacitors of the capacitor plate, wherein M is a positive integer.
3. The method of claim 2, wherein determining the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitance based on the signal characteristic of the excitation signal of the current measurement circuit and the output current comprises:
processing the M output current sequences of any one capacitor on the capacitor plate to obtain amplitudes and direct current components corresponding to the M output current sequences respectively, and obtaining M amplitudes and M direct current components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitudes, the M direct-current components and the signal characteristics.
4. The method of claim 3, wherein the signal characteristic of the excitation signal comprises a slope of the excitation signal;
the calculating gain and offset errors of the current measurement channel of the nanopore corresponding to the capacitor based on the M amplitude values, the M direct current components, and the signal characteristics includes:
calculating the measured capacitance values corresponding to the M output current sequences of the capacitor based on the M amplitude values and the slope of the excitation signal;
calculating an average measured value of the capacitance based on measured capacitance values corresponding to each of the M output current sequences of the capacitance;
calculating an average dc component of the capacitance based on the M dc components;
and calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average measurement value of the capacitor and the average direct current component of the capacitor.
5. The method of claim 4, wherein calculating the gain and offset error of the current measurement channel of the nanopore corresponding to the capacitance based on the average measured value of the capacitance and the average DC component of the capacitance comprises:
calculating the gain of the current measurement channel of the nanopore corresponding to the capacitor based on the real value of the capacitor and the average measurement value;
and calculating the offset error of the current measurement channel of the nanopore corresponding to the capacitor based on the average direct current component of the capacitor.
6. The method according to any of claims 1-5, wherein the capacitor is a picofarf capacitor.
7. The method according to any one of claims 1 to 5, wherein the excitation signal is any one of a triangular wave and a sine wave.
8. The method of any of claims 1-5, wherein obtaining the output current of any one of the capacitors on the capacitor plate comprises:
and acquiring the output current of any one capacitor on the capacitor plate through an analog-digital converter (ADC).
9. A system for determining a calibration parameter for a current measurement circuit, comprising:
the capacitive plate comprises L capacitors, the capacitors correspond to current measurement channels of the nanopore gene sequencer one by one, and L is a positive integer;
the signal processing and converting module is connected with the capacitor plate and is used for acquiring the output current of each capacitor on the capacitor plate;
a controller connected to the signal processing and converting module for performing the method of determining calibration parameters of a current measuring circuit according to any of claims 1-8;
and the power supply module is used for providing working voltage for the capacitor plate, the signal processing and converting module and the controller.
10. An apparatus for determining a calibration parameter for a current measurement circuit, comprising:
the device comprises an acquisition module, a detection module and a control module, wherein the acquisition module is used for acquiring the output current of any capacitor on a capacitor plate, the capacitors correspond to current measurement channels of a nanopore gene sequencer one by one, the capacitor plate comprises L capacitors, and L is a positive integer;
and the determining module is used for determining the gain and offset error of the current measuring channel of the nanopore corresponding to the capacitor based on the signal characteristic of the excitation signal of the current measuring circuit and the output current.
11. An electronic device, characterized in that the electronic device comprises: a processor, and a memory storing programs or instructions;
the processor, when reading and executing the program or instructions, implements a method of determining a calibration parameter for a current measurement circuit as claimed in any one of claims 1 to 8.
12. A readable storage medium, having stored thereon a program or instructions which, when executed by a processor, carry out a method of determining a calibration parameter for a current measurement circuit according to any one of claims 1 to 8.
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Application publication date: 20210430 Assignee: Chengdu Qicarbon Taike Biotechnology Co.,Ltd. Assignor: QITAN TECHNOLOGY Ltd. BEIJING Contract record no.: X2023980041526 Denomination of invention: Method, device, system, and equipment for determining calibration parameters of current measurement circuits Granted publication date: 20210713 License type: Common License Record date: 20230911 |