阅读说明：本技术 感测分子实体与纳米孔之间的相互作用 (Sensing interactions between molecular entities and nanopores ) 是由 安德鲁·约翰·赫伦 马克·约翰·布鲁斯 于 2020-05-21 设计创作，主要内容包括：一种生物化学感测系统使用传感器装置来感测分子实体与纳米孔之间的相互作用,所述传感器装置包含支撑所述纳米孔的传感器元件阵列。开关布置选择性地将用于放大感测到的电信号的检测通道连接到相应的传感器元件。基于对从所述检测通道输出的放大后电信号的分析,检测传感器元件处的相互作用的完成情况。响应于此,控制所述开关布置以将连接到其中已经检测到相互作用完成的传感器元件的所述检测通道连接到另一传感器元件。(A biochemical sensing system uses a sensor device to sense an interaction between a molecular entity and a nanopore, the sensor device including an array of sensor elements supporting the nanopore. The switch arrangement selectively connects the detection channels for amplifying the sensed electrical signals to the respective sensor elements. Detecting completion of the interaction at the sensor element based on analysis of the amplified electrical signal output from the detection channel. In response thereto, the switch arrangement is controlled to connect the detection channel connected to the sensor element in which the completion of the interaction has been detected to another sensor element.)

1. A method of sensing an interaction between a molecular entity and a nanopore, the method comprising:

providing a sensor device comprising an array of sensor elements arranged to support respective nanopores capable of interacting with a molecular entity and comprising respective electrodes, each sensor element being arranged to output an electrical signal at the electrode, the electrical signal being dependent on the interaction of a molecular entity with the nanopores;

providing a detection circuit, the detection circuit comprising:

a plurality of detection channels, each detection channel capable of amplifying an electrical signal from one of the sensor elements, the number of sensor elements in the array being greater than the number of detection channels; and

a switch arrangement capable of selectively connecting the detection channels to respective sensor elements;

controlling the switch arrangement to connect a detection channel to a respective sensor element; and

the completion of the interaction at the sensor elements is detected based on an analysis of the amplified electrical signals output from the detection channels, and in response thereto the switch arrangement is controlled to connect the respective detection channel connected to the sensor element in which the completion of the interaction has been detected to a new sensor element not currently connected to the detection channel.

2. The method of claim 1, wherein the method further comprises, after the step of controlling the switch arrangement to connect the detection channel to a sensor element that is not currently connected to a detection channel, the operations of:

determining whether a molecular entity is available for interaction at the new sensor element based on an analysis of the amplified electrical signals output from the respective detection channel, and

continuing to connect the respective detection channel to the new sensor element in response to determining that a molecular entity is available for interaction, or controlling the switch arrangement to connect the respective detection channel to another new sensor element not currently connected to a detection channel in response to determining that a molecular entity is not available for interaction.

3. A method according to claim 1 or 2, wherein the molecular entities are polymers and the sensor elements are arranged to support respective nanopores capable of interacting with the molecular entities during translocation of the molecular entities relative to the nanopores.

4. The method of claim 3, wherein the detection circuit further comprises a bias circuit arrangement capable of providing a bias signal to the sensor element, the bias signal capable of controlling the translocation of the molecular entity relative to the nanopore of the respective sensor element.

5. The method of claim 4, wherein the method further comprises controlling the bias circuit arrangement to apply a bias signal arranged to cause the translocation of the molecular entity relative to the nanopores of all of the sensor elements.

6. The method of claim 4, wherein the method further comprises causing the bias circuit arrangement to: applying a driving bias signal to a respective sensor element when the respective sensor element is connected to a detection channel, the driving bias signal being arranged to cause translocation of the molecular entity relative to the nanopore of the respective sensor element; and applying an inhibition bias signal to the respective sensor element when the respective sensor element is not connected to a detection channel, the inhibition drive signal being arranged to inhibit translocation of the molecular entity relative to the nanopore of the respective sensor element.

7. The method of claim 6, wherein the suppression drive signal is selected to suppress translocation of the molecular entity relative to the nanopore of the respective sensor element and capture molecular entities in the vicinity of the nanopore.

8. The method according to any of the preceding claims, wherein the sensor elements and/or molecular entities are adapted to capture molecular entities in the vicinity of the respective nanopore.

9. A method according to any one of the preceding claims, wherein the sensor element further comprises a capture moiety arranged to capture molecular entities in the vicinity of the respective nanopore.

10. The method of claim 8, wherein the sensor elements each include at least one capture moiety attached to the respective nanopore of the sensor element.

11. The method of any one of the preceding claims, wherein the molecular entity is a polynucleotide.

12. The method of any one of the preceding claims, wherein the nanopore is a protein pore.

13. A method according to any one of the preceding claims, wherein the sensor elements are arranged as a support membrane with nanopores inserted into the membrane.

14. A biochemical sensing system for sensing an interaction between a molecular entity and a nanopore, the biochemical sensing system comprising:

a sensor device comprising an array of sensor elements arranged to support respective nanopores capable of interacting with a molecular entity and comprising respective electrodes, each sensor element being arranged to output an electrical signal at the electrode, the electrical signal being dependent on the interaction of a molecular entity with the nanopores; and

a detection circuit, the detection circuit comprising:

a plurality of detection channels, each detection channel capable of amplifying an electrical signal from one of the sensor elements, the number of sensor elements in the array being greater than the number of detection channels;

a switch arrangement capable of selectively connecting the detection channels to respective sensor elements; and

a controller arranged to control switching of the switch arrangement to connect a detection channel to a respective sensor element,

wherein the controller is arranged to detect completion of the interaction at the sensor element based on analysis of the amplified electrical signal output from the detection channel, and in response thereto, to control the switch arrangement to connect the respective detection channel connected to the sensor element in which completion of the interaction has been detected to another sensor element not currently connected to the detection channel.