阅读说明：本技术 电流测量设备、分子实体感测设备、测量电流的方法、感测分子实体的方法 (Current measurement device, molecular entity sensing device, method of measuring current, method of sensing molecular entity ) 是由 D·菲施 H·文斯特拉 E·托泰 于 2020-02-04 设计创作，主要内容包括：提供了用于测量电流的方法和设备。在一种布置中,第一电荷放大器对待测电流进行积分。处理电路使用第一低通滤波器模块和第二低通滤波器模块对来自所述第一电荷放大器的输出进行滤波。第二电荷放大器对源自来自所述第一电荷放大器的经滤波输出的电流进行积分。所述设备被配置成在多个感测帧中的每个感测帧开始时对所述第一电荷放大器进行复位。所述处理电路在每个感测帧内获得来自所述第一电荷放大器的所述输出的至少第一样本。对所述第一样本的采样从一个感测帧到下一个感测帧在通过所述第一低通滤波器模块进行的采样与通过所述第二低通滤波器模块进行的采样之间交替。(Methods and apparatus for measuring current are provided. In one arrangement, a first charge amplifier integrates the current to be measured. A processing circuit filters an output from the first charge amplifier using a first low pass filter module and a second low pass filter module. A second charge amplifier integrates current derived from the filtered output from the first charge amplifier. The apparatus is configured to reset the first charge amplifier at the beginning of each of a plurality of sensing frames. The processing circuit obtains at least a first sample from the output of the first charge amplifier within each sense frame. The sampling of the first samples alternates between sampling by the first low pass filter module and sampling by the second low pass filter module from one sensing frame to the next.)

1. A current measurement apparatus, comprising:

a first charge amplifier configured to integrate a current to be measured;

a processing circuit configured to filter an output from the first charge amplifier using a first low pass filter module and a second low pass filter module; and

a second charge amplifier configured to integrate current derived from the filtered output from the first charge amplifier, wherein:

the device is configured to reset the first charge amplifier at the beginning of each of a plurality of sensing frames;

the processing circuit is configured to obtain at least a first sample from the output of the first charge amplifier within each sensing frame; and is

Sampling of the first sample

From one sensing frame to the next sensing frame

Sampling and by the first low pass filter module

The sampling by the second low pass filter module alternates between.

2. The apparatus of claim 1, wherein the first low pass filter module comprises a first RC filter and the second low pass filter module comprises a second RC filter.

3. The apparatus of claim 2, configured such that either or both of the following conditions are satisfied:

storing a first sample from a previous sensing frame in the form of a charge on a capacitive component of the first RC filter during each sensing frame in which sampling of the first sample was not performed by the first low pass filter module; and

in each sense frame in which sampling of the first sample is not performed by the second low pass filter module, the first sample from a previous sense frame is stored in the form of a charge on a capacitive component of the second RC filter.

4. A device according to claim 3, configured such that either or both of the following conditions are satisfied:

the capacitive component of the first RC filter comprises a first plurality of capacitors and applies a selected attenuation to charge representing information about the current under test by sampling charge from only a selected subset of the first plurality of capacitors within each sensing frame in which sampling of the first sample is performed by the first low pass filter module; and is

The capacitive component of the second RC filter comprises a second plurality of capacitors and applies a selected attenuation to charge representing information about the current to be measured by sampling charge from only a selected subset of the second plurality of capacitors within each sensing frame in which sampling of the first sample is performed by the second low pass filter module.

5. The apparatus of any preceding claim, configured such that the first and second samples from the output of the first charge amplifier are obtained within each sensing frame, and the processing circuitry is configured to perform correlated double sampling using the first and second samples.

6. The apparatus of claim 5, wherein:

the processing circuit further comprises at least one further low-pass filter module; and is

The device is configured to sample the second samples by the at least one further low-pass filter module.

7. The apparatus of claim 6, wherein:

said at least one further low-pass filter module consists of a further low-pass filter module; and is

The device is configured such that for all sensing frames, said sampling of said second samples is performed only by said further low-pass filter module.

8. The apparatus of claim 7, configured such that each of the first low pass filter module, the second low pass filter module and the further low pass filter module obtains samples within each sensing frame in which the respective low pass filter module is reset.

9. The apparatus of claim 8, configured such that the resetting of the low pass filter modules is performed by bypassing a resistive component of an RC filter of each low pass filter module.

10. The apparatus of claim 8 or 9, configured such that the timing of the resetting of each low pass filter module is such that the samples are obtained an equal time after the resetting of each low pass filter module that samples each of the first and second samples.

11. The apparatus of claim 6, wherein the at least one further low pass filter module comprises a third low pass filter module and a fourth low pass filter module, and the apparatus is configured such that the sampling of the second samples alternates between sampling by the third low pass filter module and sampling by the fourth low pass filter module from one sensing frame to the next.

12. The apparatus of any preceding claim, configured such that the difference between the first and second samples within each sensing frame is implemented by combining an output from the low pass filter module storing charge corresponding to the first sample with an output from the low pass filter module storing charge corresponding to the second sample of opposite polarity.

13. The apparatus of any preceding claim, wherein the first charge amplifier is configured such that the integration of the current is performed simultaneously across a first capacitive element and a second capacitive element, and the resetting of the first charge amplifier is performed by allowing charge stored on the second capacitive element to flow onto the first capacitive element and at least partially cancelling charge stored on the first capacitive element.

14. A current measurement apparatus, comprising:

a first charge amplifier configured to integrate a current to be measured;

a processing circuit configured to filter an output from the first charge amplifier; and

a second charge amplifier configured to integrate current derived from the filtered output from the first charge amplifier, wherein:

the first charge amplifier is configured such that the integration of the current is performed simultaneously across a first capacitive element and a second capacitive element, and the resetting of the first charge amplifier is performed by allowing charge stored on the second capacitive element to flow onto the first capacitive element and at least partially cancelling charge stored on the first capacitive element.

15. The apparatus of claim 14, wherein: the sampling of the first samples alternates between sampling by the first low pass filter module and sampling by the second low pass filter module from one sensing frame to the next.

16. The apparatus of any preceding claim, wherein the processing circuitry is configured such that information about the current to be measured propagates through the processing circuitry from the first charge amplifier to the second charge amplifier only in the form of an amount representative of the charge of the current to be measured.

17. A current measurement apparatus, comprising:

a first charge amplifier configured to integrate a current to be measured;

a processing circuit configured to filter an output from the first charge amplifier; and

a second charge amplifier configured to integrate current derived from the filtered output from the first charge amplifier, wherein:

the processing circuit is configured such that information about the current to be measured propagates through the processing circuit from the first charge amplifier to the second charge amplifier in the form of an amount representing a charge of the current to be measured.

18. The apparatus of any preceding claim, wherein the processing circuitry consists only of passive components and externally controllable switches.

19. A molecular entity sensing apparatus, comprising:

a sensor arrangement comprising an array of sensor elements, each sensor element being arranged to output a current dependent on an interaction between a molecular entity and the sensor element; and

a plurality of current measurement devices according to any preceding claim, wherein each current measurement device is configured to measure the current output by one or more of the sensor elements and to provide an output that is dependent on the current output by the one or more of the sensor elements.

20. The apparatus of claim 19, wherein: each of the sensor elements comprises a nanopore.

21. The device of claim 19 or 20, wherein the nanopore comprises a membrane protein or a solid state nanopore.

22. The device of any one of claims 19 to 21, wherein the sensor elements are each arranged as an amphiphilic membrane into which a support membrane protein can be inserted.

23. A method of measuring current, the method comprising:

integrating the current to be measured by using a first charge amplifier;

filtering an output from the first charge amplifier using a first low pass filter module and a second low pass filter module; and

integrating a current derived from the filtered output from the first charge amplifier using a second charge amplifier, wherein:

resetting the first charge amplifier at the beginning of each of a plurality of sensing frames;

obtaining at least a first sample from the output of the first charge amplifier within each sense frame; and is

The sampling of the first samples alternates between sampling by the first low pass filter module and sampling by the second low pass filter module from one sensing frame to the next.

24. A method of measuring current, the method comprising:

integrating the current to be measured by using a first charge amplifier;

filtering an output from the first charge amplifier; and

integrating a current derived from the filtered output from the first charge amplifier using a second charge amplifier, wherein:

performing the integration of the current by the first charge amplifier simultaneously across a first capacitive element and a second capacitive element, and performing the resetting of the first charge amplifier by allowing charge stored on the second capacitive element to flow onto the first capacitive element and at least partially cancelling charge stored on the first capacitive element.

25. A method of measuring current, the method comprising:

integrating the current to be measured by using a first charge amplifier;

filtering an output from the first charge amplifier using a processing circuit; and

integrating a current derived from the filtered output from the first charge amplifier using a second charge amplifier, wherein:

the processing circuit is configured such that information about the current to be measured propagates through the processing circuit from the first charge amplifier to the second charge amplifier in the form of an amount representing a charge of the current to be measured.

26. A method of sensing a molecular entity, the method comprising measuring a current dependent on an interaction between the molecular entity and a sensor element using the method of any one of claims 23 to 25.