WO2021121389A1

WO2021121389A1 - Circuit with bidirectional current source for generating acidic or basic microenvironment in solution

Info

Publication number: WO2021121389A1
Application number: PCT/CN2020/137617
Authority: WO
Inventors: Yung-Lung Lin; Jianpeng Wang
Original assignee: Nanjing GenScript Biotech Co., Ltd.
Priority date: 2019-12-19
Filing date: 2020-12-18
Publication date: 2021-06-24
Also published as: CN115210572A

Abstract

Provided is a circuit for generating and subsequently neutralizing an acidic or basic microenvironment in a solution, comprising: a first output terminal connected to a first node of a container which contains the solution; a second output terminal connected to a second node of the container; a control sub-circuit configured to provide control signals controlling the circuit; and a current source sub-circuit configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit; wherein the first direction current generates an acidic microenvironment in the solution around the first node and/or a basic microenvironment in the solution around the second node, and the second direction current generates a basic microenvironment in the solution around the first node and/or an acidic microenvironment in the solution around the second node.

Description

[Title established by the ISA under Rule 37.2] CIRCUIT WITH BIDIRECTIONAL CURRENT SOURCE FOR GENERATING ACIDIC OR BASIC MICROENVIRONMENT IN SOLUTION

TECHNICAL FIELD

Generally, this application relates to the field of synthesis of biological macromolecules, e.g., oligopeptides and oligonucleotides. Particularly, this application relates to a circuit with a bidirectional current source for generating an acidic or basic microenvironment in an Echem solution.

BACKGROUND OF THE INVENTION

Using the in situ array technology, the synthesis of oligonucleotides can benefit from the same parallelization that has revolutionized the DNA sequencing field. Leveraging the semi-conductor industry to achieve the most reproducible and high-throughput synthesis is possible. Fastest synthesis in the industry with high sequence fidelity can be implemented due to the flexibility of using a simple synthesizer with an advanced chip.

When performing nucleotide addition, first, an Echem solution is delivered so as to deblock (or deprotection, particularly detritylation) DNA strands and make them ready to receive the next base. Then, an electric potential is applied at the electrodes on the chip surface, which generates a localized acidic environment, so as to effectively deblock the DNA strands.

However, uncontrollable or too much acids will cause oligo depletion and result in high error rate.

SUMMARY OF THE INVENTION

This invention provides a circuit with a bidirectional current source that can generate and subsequently neutralize an acid or basic microenvironment in a solution in a controllable way.

In one example aspect, a circuit for generating an acidic or basic microenvironment in a solution (e.g., an Echem solution) , for example, during nucleotide addition, is disclosed. The circuit comprises: a first output terminal connected to a first node (corresponding to a spot for synthesis) of a container which contains a solution; a second output terminal connected to a second node of the container; a control sub-circuit configured to provide control signals controlling the circuit; and a current source sub-circuit configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit; wherein the first direction current generates an acidic microenvironment in the solution around the first node and/or a basic microenvironment in the solution around the second node, and the second direction current generates a basic microenvironment in the solution around the first node and/or an acidic microenvironment in the solution around the second node. In one embodiment, the first direction current is first used to generate an acidic or basic microenvironment, and then the second direction current is used to neutralize the acidic or basic microenvironment generated by the first direction current. In another embodiment, the second direction current is first used to generate a basic or acidic microenvironment, and then the first direction current is used to neutralize the basic or acidic microenvironment generated by the second direction current.

In another example aspect, an apparatus for generating an acidic or basic microenvironment in a solution is disclosed. The apparatus comprises: a plurality of containers, each container having a first node and a second node, the container configured to contain a solution; and a circuit of the above example aspect.

The details of one or more implementations are set forth in the accompanying attachments, the drawings, and the description below. Other features will be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1a and 1b illustrate selective deprotection by electrochemically generated acids.

FIG. 2 illustrates an example of container.

FIG. 3 illustrates an example block diagram of the apparatus of the present application.

FIG. 4 illustrates a first example circuit diagram of the present application.

FIG. 5 illustrates a second example circuit diagram of the present application.

FIG. 6 illustrates a third example circuit diagram of the present application.

DETAILED DESCRIPTION OF THE INVENTION

A circuit and apparatus for generating an acidic or basic microenvironment in a solution are described. It should be noted that various embodiments described in the present disclosure may be practiced without some or all of these specific details. In other instances, well known process operations have not been described in detail in order not to unnecessarily obscure various embodiments described in the present disclosure.

When using the in situ array technology, the synthesis of oligonucleotides can benefit from the same parallelization that has revolutionized the DNA sequencing field. Leveraging the semi-conductor industry to achieve the most reproducible and high-throughput synthesis is possible. Fastest synthesis in the industry with high sequence fidelity can be implemented due to the flexibility of using a simple synthesizer with an advanced chip.

Each nucleotide addition requires 4 steps.

a) Detritylation Step

In Detritylation Step, delivering an Echem solution to deblock DNA strands so as to make them ready to receive the next base. An electric potential is applied at the electrodes on the chip surface, which generates a localized acidic environment so as to effectively deblock the DNA strands.

b) Coupling Step

In Coupling Step, delivering an amidite (A, C, G, or T) solution with an activator solution to the chip surface. This step results in the lengthening of the strands with the addition of a new base.

c) Capping Step

In Capping Step, the capping mixture reacts with the strands that did not receive a base during the coupling step and permanently stops their growth. Capping helps avoid having a significant amount of strands with single base pair deletions that will give errant results during the assay.

d) Oxidation Step

In Oxidation Step, delivering an oxidizer solution to the chip surface. The oxidation finalizes the chemistry for the added base.

e) Repeat

The cycle is typically repeated in the A-C-G-T order, meaning that during cycle 1, amidite A will be delivered, during cycle 2, amidite C will be delivered, and so on. Only the spots on the surface that have been prepared during the Echem step will receive a base during that cycle.

The solution used in the present invention can be any deblocking solution available in the art for synthesis of oligonucleotides or oligopeptides, e.g., a solution comprising a redox deblocking system, particularly hydroquinone-benzoquinone redox system. For example, the solution can be an Echem solution, which is 25 mM of benzoquinone, 25 mM of hydroquinone, and 25 mM of tetrabutylammonium hexafluorophosphate in acetonitrile.

Figs. 1a and 1b illustrate selective deprotection by electrochemically generated acid (protons) generated at electrodes 1 and 4 to expose reactive functionalities (NH ₂) on the linker molecules (L) proximate electrodes 1 and 4. The substrate is shown in cross section and contains 5 electrodes.

FIG. 2 illustrates an example of the container.

The container is formed on a substrate of a semiconductor chip. In fact, there is a substrate array on the semiconductor chip, and each substrate (such as an electrode) can act as a container. As shown in Fig. 2, during the detritylation step, a circuit under the selected electrode can generate a current from Node1 to Node2. Using current source and MOS switch controlled by SRAM (selected or unselected) , a current is generated from Node1 to Node2, resulting in an acidic microenvironment in the Echem solution around Node1.

As shown in Fig. 3, the apparatus 300 of the present application includes a selection circuit 301, a control circuit 302 and a plurality of containers 303. The selection circuit 301 selects one or more containers 303. The control circuit 302 can electrically couple to the selected container 303. The example of container 303 is shown in Fig. 2.

When one container 303 is selected, a current is generated from Node1 to Node2 of the selected container by the control circuit 302 so as to result in an acidic microenvironment in the Echem solution of the container 303 around Node1.

However, uncontrollable or too much acids will cause oligo depletion and result in high error rate. Therefore, the control circuit 302 of the present application can generate a bidirectional current. The initial direction current is to generate an acidic microenvironment at the beginning of the detritylation step, and the subsequent, opposite current is to neutralize said acidic microenvironment at the end of the detritylation step. As a result, it can generate and neutralize an acidic microenvironment in a controllable and rapid way.

FIG. 4 illustrates a first example of the control circuit of the present application. As shown in Fig. 4, the control circuit 400 includes a first output terminal (Out1) connected to a first node (Node1) of the container 303 and a second output terminal (Out2) connected to a second node (Node2) of the container 303. Since the container 303 contains a solution (such as an Echem solution) , when a current flows from Node2 to Node 1 or from Node1 to Node2, the solution can be regarded as a load resistor R1.

The control circuit 400 includes a control sub-circuit 401 configured to provide control signals controlling the circuit 400. For example, the control sub-circuit 401 can provide control signals according to the detritylation step occurring in the container.

In addition, the control circuit 400 includes a current source sub-circuit 402 configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit.

In particular, the current source sub-circuit 402 includes two current sources, S1 and S2. The current source S1 can provide the second direction current flowing from the second node (Node2) to the first node (Node1) via the second output terminal (Out2) . The current source S2 can provide the first direction current flowing from the first node (Node1) to the second node (Node2) via the first output terminal (Out1) . In the solution of the container, when S2 works, the first direction current generates an acidic microenvironment in the solution around the first node (Node1) , and when S1 works, the second direction current neutralizes said acidic microenvironment in the solution around the first node (Node1) .

In addition, the control circuit 400 includes an enable sub-circuit 403 disposed between the current source sub-circuit 402 and the first output terminal (Out1) . For example, the selection sub-circuit is a MOS transistor (J3) normally. The MOS transistor is turned on in response to a SRAM signal provided by the selection circuit 301. When the MOS transistor is turned on, it can enable S1 of the current source sub-circuit 402 to flow from Node2 to Node1 or enable S2 of the current source sub-circuit 402 to flow from Node1 to Node2.

In addition, the control circuit 400 includes a switch sub-circuit 404. In this embodiment, for example, the switch sub-circuit includes a single-pole, double-throw (SPDT) switch (SW1) , which has a first terminal, a second terminal and a third terminal. As shown in Fig. 4, the first terminal is connected to the second output terminal (Out2) , the second terminal is connected to the first current source (S1) , and the third terminal is connected to the second current source (S2) .

The SPDT switch SW1 selectively connects the first terminal and the second terminal or connects the first terminal and the third terminal in response to the control signals provided by the control sub-circuit 401.

For example, at the beginning of the detritylation step, the SPDT switch SW1 connects Out2 and S2, so that the current from S2 can flow from Node1 to Node2. At this stage, the current generates an acidic microenvironment around Node1, and effectively deblocks the DNA strands attached to Node1.

Then, at the end of the detritylation step, the SPDT switch SW1 connects Out2 and S1, so that the current from S1 can flow from Node2 to Node1. At this stage, the current can neutralize the above acidic microenvironment around Node1 in a controllable and rapid way.

That is, the control signals provided by the control sub-circuit 401 are determined by the detritylation step occurring in the container 303.

Therefore, with the circuit of the first embodiment, it can flow the current from Node1 to Node2 so as to generate an acidic microenvironment around Node1 in the Echem solution of the container at the beginning of the detritylation step, and flow the current from Node2 to Node1 so as to neutralize the acidic microenvironment around Node1 in the Echem solution at the end of the detritylation step. As a result, it can reduce error rate.

FIG. 5 illustrates a second example of the control circuit of the present application. As shown in FIG. 5, the control circuit 500 includes a first output terminal (Out1) connected to a first node (Node1) of the container 303 and a second output terminal (Out2) connected to a second node (Node2) of the container 303. Since the container 303 contains a solution (such as an Echem solution) , when a current flows from Node2 to Node1 or from Node1 to Node2, the solution can be regarded as a load resistor R1.

The control circuit 500 includes a control sub-circuit 501 configured to provide control signals controlling the circuit 500. For example, the control sub-circuit 501 can provide control signals according to the detritylation step occurring in the container.

In addition, the control circuit 500 includes a current source sub-circuit 502 configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit.

In particular, the current source sub-circuit 502 includes two current sources, S1 and S2. The current source S1 can provide the second direction current flowing from the second node (Node2) to the first node (Node1) via the second output terminal (Out2) . The current source S2 can provide the first direction current flowing from the first node (Node1) to the second node (Node2) via the first output terminal (Out1) . In the solution of the container, when S2 works, the first direction current generates an acidic microenvironment in the solution around the first node (Node1) , and when S1 works, the second direction current neutralizes said acidic microenvironment in the solution around the first node (Node1) .

In addition, the control circuit 500 includes an enable sub-circuit 503 disposed between the current source sub-circuit 502 and the first output terminal (Out1) . For example, the selection sub-circuit is a MOS transistor (J3) normally. The MOS transistor is turned on in response to a SRAM signal provided by the selection circuit 301. When the MOS transistor is turned on, it can enable S1 of the current source sub-circuit 502 to flow from Node2 to Node1 or enable S2 of the current source sub-circuit 502 to flow from Node1 to Node2.

In addition, the control circuit 500 includes a switch sub-circuit 504. In this embodiment, for example, the switch sub-circuit includes a single-pole, double-throw (SPDT) switch (SW1) , which has a first terminal, a second terminal and a third terminal. As shown in FIG. 5, the first terminal is electrically connected to the first output terminal (Out1) via the enable sub-circuit 503, the second terminal is connected to the first current source (S1) , and the third terminal is connected to the second current source (S2) .

The SPDT switch SW1 selectively connects the first terminal and the second terminal or connects the first terminal and the third terminal in response to the control signals provided by the control sub-circuit 501.

For example, at the beginning of the detritylation step, the SPDT switch SW1 connects Out1 and S2, so that the current from S2 can flow from Node1 to Node2. At this stage, the current generates an acidic microenvironment around Node1, and effectively deblocks the DNA strands attached to Node1.

Then, at the end of the detritylation step, the SPDT switch SW1 connects Out1 and S1, so that the current from S1 can flow from Node2 toNode1. At this stage, the current can neutralize the above acidic microenvironment around Node1 in a controllable and rapid way.

That is, the control signals provided by the control sub-circuit 501 are determined by the detritylation step occurring in the container 303.

Therefore, with the circuit of the second embodiment, it can flow the current from Node1 to Node2 so as to generate an acidic microenvironment around Node1 in the Echem solution of the container at the beginning of the detritylation step, and flow the current from Node2 to Node1 so as to neutralize the acidic microenvironment around Node1 in the Echem solution at the end of the detritylation step. As a result, it can reduce error rate.

FIG. 6 illustrates a third example of the control circuit of the present application. As shown in FIG. 6, the control circuit 600 includes a first output terminal (Out1) connected to a first node (Node1) of the container 303 and a second output terminal (Out2) connected to a second node (Node2) of the container 303. Since the container 303 contains a solution (such as an Echem solution) , when a current flows from Node2 to Node1 or from Node1 to Node2, the solution can be regarded as a load resistor R1.

The control circuit 600 includes a control sub-circuit 601 configured to provide control signals controlling the circuit 600. For example, the control sub-circuit 601 can provide the control signals according to the detritylation step occurring in the container.

In addition, the control circuit 600 includes a current source sub-circuit 602 configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit.

In particular, the current source sub-circuit 602 includes two current sources, S1 and S2. The current source S1 can provide the second direction current flowing from the second node (Node2) to the first node (Node1) via the second output terminal (Out2) . The current source S2 can provide the first direction current flowing from the first node (Node1) to the second node (Node2) via the first output terminal (Out1) . In the solution of the container, when S2 works, the first direction current generates an acidic microenvironment in the solution around the first node (Node1) , and when S1 works, the second direction current neutralizes said acidic microenvironment in the solution around the first node (Node1) .

In addition, the control circuit 600 includes an enable sub-circuit 603 disposed between the current source sub-circuit 602 and the first output terminal (Out1) . For example, the selection sub-circuit is a MOS transistor (J3) normally. The MOS transistor is turned on in response to a SRAM signal provided by the selection circuit 301. When the MOS transistor is turned on, it can enable S1 of the current source sub-circuit 602 to flow from Node2 to Node1 or enable S2 of the current source sub-circuit 602 to flow from Node1 to Node2.

In addition, the control circuit 600 includes a pair of switch sub-circuits, 604a and 604b. In this embodiment, for example, the pair of switch sub-circuits includes two signal switches, SW1a and SW1b. The switch SW1a has a first terminal and a second terminal, the first terminal is connected to the first current source (S1) , and the second terminal is electrically connected to the second output terminal (Out2) . The switch SW1b has a third terminal and a fourth terminal, the third terminal is connected to the second current source (S2) , and the fourth terminal is connected to the first output terminal (Out1) via the enable sub-circuit 603.

For example, at the beginning of the detritylation step, the switch SW1a disconnects S1 and Out2 in response to the control signals provided by the control sub-circuit 601. At the same time, the switch SW1b connects S2 and Out1 in response to the control signals provided by the control sub-circuit 601. Thus, the current from S2 can flow from Node1 to Node2. At this stage, the current generates an acidic microenvironment around Node1, and effectively deblocks the DNA strands attached to Node1.

Then, at the end of the detritylation step, the switch SW1b disconnects S2 and Out1 in response to the control signals provided by the control sub-circuit 601. At the same time, the switch SW1a connects S1 and Out2 in response to the control signals provided by the control sub-circuit 601. Thus, the current from S1 can flow from Node2 to Node1. At this stage, the current can neutralize the above acidic microenvironment around Node1 in a controllable and rapid way.

That is, the control signals provided by control sub-circuit 601 are determined by the detritylation step occurring in the container 303.

Therefore, with the circuit of the third embodiment, it can flow the current from Node1 to Node2 so as to generate an acidic microenvironment around Node1 in the Echem solution of the container at the beginning of the detritylation step, and flow the current from Node2 to Node1 so as to neutralize the acidic microenvironment around Node1 in the Echem solution at the end of the detritylation step. As a result, it can reduce error rate.

The disclosed and other embodiments, modules and the functional operations described in this document can be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this document and their structural equivalents, or in combinations of one or more of them. The disclosed and other embodiments can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a computer readable medium for execution by, or to control the operation of, data processing apparatus. The computer readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of matter effecting a machine-readable propagated signal, or a combination of one or more them. The term “data processing apparatus” encompasses all apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, or multiple processors or computers. The apparatus can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them. A propagated signal is an artificially generated signal, e.g., a machine-generated electrical, optical, or electromagnetic signal, that is generated to encode information for transmission to suitable receiver apparatus.

A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document) , in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code) . A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

The processes and logic flows described in this document can be performed by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit) .

Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor will receive instructions and data from a read only memory or a random-access memory or both. The essential elements of a computer are a processor for performing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. However, a computer need not have such devices. Computer readable media suitable for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks; magneto optical disks; and CD ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

While this document contains many specifics, these should not be construed as limitations on the scope of any invention or of what may be claimed, but rather as descriptions of features that may be specific to particular embodiments of particular inventions. Certain features that are described in this patent document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.

Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Moreover, the separation of various system components in the embodiments described in this patent document should not be understood as requiring such separation in all embodiments.

Only a few implementations and examples are described and other implementations, enhancements and variations can be made based on what is described and illustrated in this patent document.

Claims

A circuit for generating an acidic or basic microenvironment in a solution, comprising:

a first output terminal connected to a first node of a container which contains the solution;

a second output terminal connected to a second node of the container;

a control sub-circuit configured to provide control signals controlling the circuit; and

a current source sub-circuit configured to selectively provide a first direction current flowing from the first node to the second node via the first output terminal, or a second direction current flowing from the second node to the first node via the second output terminal, under the control of the control signals from the control sub-circuit;

wherein the first direction current generates an acidic microenvironment around the first node and/or a basic microenvironment around the second node in the solution, and the second direction current generates a basic microenvironment around the first node and/or an acidic microenvironment around the second node in the solution.
The circuit of claim 1, wherein the current source sub-circuit comprises a first current source which provides the second direction current and a second current source which provide the first direction current.
The circuit of claim 2, further comprising:

a switch sub-circuit comprising a switch having a first terminal, a second terminal and a third terminal, wherein the first terminal is connected to the first output terminal, the second terminal is connected to the first current source, and the third terminal is connected to the second current source.
The circuit of claim 2, further comprising:

a switch sub-circuit comprising a switch having a first terminal, a second terminal and a third terminal, wherein the first terminal is connected to the second output terminal, the second terminal is connected to the first current source, and the third terminal is connected to the second current source.
The circuit of claim 3 or 4, wherein

the switch sub-circuit selectively connects the first terminal and the second terminal or connects the first terminal and the third terminal in response to the control signals provided by the control sub-circuit.
The circuit of claim 5, wherein the control signals provided by the control sub-circuit are determined by the detritylation step occurring in the container.
The circuit of claim 6, wherein

the switch sub-circuit connects the first terminal and the third terminal so as to flow the first direction current from the first node to the second node at the beginning of the detritylation step, and

the switch sub-circuit connects the first terminal and the second terminal so as to flow the second direction current from the second node to the first node at the end of the detritylation step.
The circuit of claim 2, further comprising:

a pair of switch sub-circuits comprising a first sub-switch and a second sub-switch, wherein the first sub-switch has a first terminal and a second terminal, the first terminal being connected to the first current source, and the second terminal being connected to the first output terminal, and the second sub-switch has a third terminal and a fourth terminal, the third terminal being connected to the second current source, and the fourth terminal being connected to the second output terminal.
The circuit of claim 8, wherein

the pair of switch sub-circuits selectively turns on one of the first sub-switch and the second sub-switch and turns off the other one in response to the control signals provided by the control sub-circuit.
The circuit of claim 9, wherein the control signals provided by the control sub-circuit are determined by the detritylation step occurring in the container.
The circuit of claim 10, wherein

the pair of switch sub-circuits turns off the first sub-switch and turns on the second sub-switch so as to flow the first direction current from the first node to the second node at the beginning of the detritylation step, and

the pair of switch sub-circuits turns off the second sub-switch and turns on the first sub-switch so as to flow the second direction current from the second node to the first node at the end of the detritylation step.
The circuit of claim 2, further comprising:

an enable sub-circuit disposed between the current source sub-circuit and the first output terminal, the selection sub-circuit being configured to enable the first direction current or the second direction current of the current source sub-circuit to flow in response to a selection signal from outside.
The circuit of claim 1, wherein

the container is formed on one substrate of a substrate array of a semiconductor chip, and the solution in the container is a deblocking solution comprising a redox system.
An apparatus for generating an acidic or basic microenvironment in a solution, comprising:

a plurality of containers, each container having a first node and a second node, the container configured to contain the solution; and

a circuit according to any one of claims 1 to 13.
The apparatus of claim 14, wherein

each container is formed on one substrate of a substrate array of a semiconductor chip, and the solution in the container is a deblocking solution comprising a redox system.
The apparatus of claim 15, further comprising:

a selection circuit configured to select one of the containers so as to generate an acidic or basic microenvironment in the solution of the selected container.