Molecular synthesis array
Through the cross-rod structure and the molecular synthesis array coupled with the selection transistor, the problems of electrode wiring complexity and density limitation are solved, high-density synthesis position and selective addressing are achieved, crosstalk risk is reduced, and synthesis efficiency is improved.
Patent Information
- Application Number
- CN202380041857.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-05-31
- Filing Date
- 2023-05-26
- Publication Date
- 2025-01-07
AI Technical Summary
The existing molecular synthetic microarrays face complex electrode wiring and density limitations during the scaling process, resulting in low synthesis position density and difficulty in selective addressing.
The molecular synthesis array with cross-rod structure is adopted to achieve high-density synthesis positions through the cross arrangement of column lines and row lines, and the crosstalk between adjacent synthesis holes is reduced by selecting the coupling structure of transistors and electrodes, and the potential of the synthesis hole itself is replaced by Special capacitors to reduce the number of electrode connections.
Arrays of high-density synthetic positions are realized, reducing the risk of crosstalk between adjacent synthetic holes, simplifying the manufacturing process, and improving the efficiency and area efficiency of the synthesis process through time division multiplexing schemes.
Smart Images
Figure CN119278096A_ABST
Abstract
Description
Technical Field
[0001] The inventive concept relates to a molecular synthesis array, a molecular synthesis device, a data storage system including the molecular synthesis device, and a method for realizing synthesis in the molecular synthesis device. Background Art
[0002] DNA (deoxyribonucleic acid) chips provide a collection of nucleic acid chains fixed at defined positions on a solid surface. DNA chips allow high-throughput electrochemical synthesis of DNA and have become a core technology in the fields of bioanalysis and biomedical diagnosis. Recently, in addition to traditional gene expression experiments, DNA microarrays have become a powerful tool in many other research fields, such as for gene assembly, DNA origami, or as a platform for data storage.
[0003] DNA chip can comprise electrode arrays, and these electrode arrays provide the electrochemically controlled in-situ synthesis of different oligonucleotides at the limited position in the array.As the progress of micro-fabrication technology enables scaling electrodes, it is envisioned that such arrays have the potentiality of allowing high-density and high-throughput DNA synthesis.Although the arrays mentioned above for DNA synthesis, this technology is not limited to the synthesis of DNA, but can be used for the synthesis of organic molecules such as polymers, DNA or ribonucleic acids (RNA) more generally.
[0004] To date, microarrays for molecular synthesis have typically relied on a structure in which each electrode (and therefore each synthesis position) is addressed individually. While this can facilitate selective addressing of synthesis positions, it makes scaling more challenging because the increased number of electrodes complicates the wiring of the electrodes and because the area required for wiring will limit the density of electrodes. This may actually limit the density of synthesis positions that can be achieved in the array. Summary of the invention
[0005] In view of the above, it would be desirable to provide a molecular synthesis array that can realize a relatively large number of synthesis positions (that is, high-density synthesis positions) in a relatively small area, such as to help store a large amount of data in the array. Simultaneously, it would be desirable to selectively address each synthesis position to provide a separate control of the building-up reaction at each synthesis position (that is, avoiding activating adjacent synthesis positions). The purpose of the inventive concept is to address these needs. Further and alternative purposes can be understood from hereinafter.
[0006] According to a first aspect of the present invention, a molecular synthesis array is provided. The molecular synthesis array includes: a substrate; an insulating layer, the insulating layer is arranged on the substrate; a plurality of column lines and a plurality of row lines, the plurality of column lines extend in parallel along the column direction of the molecular synthesis array, the plurality of row lines extend in parallel along the row direction of the molecular synthesis array, wherein the column lines are vertically separated from the row lines and extend transversely to the row lines; a plurality of synthesis units, wherein each unit is coupled to a corresponding pair of column lines and row lines and includes: a lower electrode and an upper electrode, the lower electrode and the upper electrode are vertically separated from each other and embedded in the insulating layer; a synthesis hole, the synthesis hole extends from the upper surface of the insulating layer through the insulating layer and penetrates extending through the upper electrode to the lower electrode, wherein the hole exposes a surface portion of the upper electrode and a surface portion of the lower electrode; and a selection transistor having a first terminal, a second terminal and a gate terminal, the first terminal and the second terminal forming respective source / drain terminals of the selection transistor, wherein the gate terminal is coupled to a row line, the first terminal is coupled to a column line, the second terminal is coupled to the lower electrode, and the upper electrode is coupled to a reference voltage, or wherein the gate terminal is coupled to the row line, the first terminal is coupled to the column line, the second terminal is coupled to the upper electrode, and the lower electrode is coupled to a reference voltage.
[0007] The molecular synthesis array of the first aspect of the present invention can achieve many advantages:
[0008] (i) increasing the feasibility of area-efficient synthesis arrays with a large number of synthesis locations,
[0009] (ii) The pore structure at the synthesis site reduces the risk of crosstalk between adjacent synthesis pores,
[0010] (iii) less complexity during manufacturing due to the reduced need for a separate dedicated capacitor (as the potential in the synthetic aperture itself can be utilized instead), and
[0011] (iv) The number of electrode connections required scales with the square root of the number of electrodes, rather than with the number of electrodes as in an array where each electrode (and therefore each synthesis position) is addressed individually.
[0012] These advantages may be better and more fully understood from the following.
[0013] According to the molecular synthesis array, an array of synthesis units can be defined, wherein each synthesis unit (or more specifically, its synthesis hole) can define a corresponding synthesis position (i.e., synthesis point), i.e., a position in the array where a molecular synthesis reaction can be achieved by electrically activating the column lines and row lines coupled to the electrodes of the synthesis unit. More specifically, the molecular synthesis array and its synthesis holes can be supplied with a molecular synthesis medium, such as a liquid solution containing reagents for the synthesis reaction, in use.
[0014] The upper and lower electrodes (or more specifically, the surface portions of the upper and lower electrodes exposed at each synthetic hole) can be configured to control the reaction conditions at the corresponding synthetic unit. The surface portion at each synthetic hole can be configured to enable or inhibit a chemical reaction in the molecular synthesis medium in response to being activated. The molecular synthesis medium of each synthetic hole (and any reagents supplied to the synthetic hole) can be such that the chemical reaction will be inhibited (i.e., will not occur) unless the associated electrode is activated. Alternatively, the molecular synthesis medium of each synthetic hole can be such that the chemical reaction will be enabled (i.e., will occur) unless the associated electrode is activated. In other words, depending on the specific synthesis type, the electrode can be configured to enable a reaction or inhibit a reaction when activated.
[0015] According to the molecular synthesis array, the gate terminal can be coupled to the row line, the first terminal can be coupled to the column line, the second terminal can be coupled to the lower electrode, and the upper electrode can be coupled to the reference voltage. This configuration of the synthesis unit may be referred to as the "first unit configuration" hereinafter. Alternatively, the gate terminal may be coupled to the row line, the first terminal may be coupled to the column line, the second terminal may be coupled to the upper electrode, and the lower electrode may be coupled to the reference voltage. This configuration of the synthesis unit may be referred to as the "second unit configuration" hereinafter.
[0016] In both the first cell configuration and the second cell configuration, the reference voltage may be a fixed reference voltage (eg, ground voltage) or a reference voltage switchable between a first reference voltage level and a second reference voltage level (eg, ground voltage and a positive reference voltage).
[0017] "Activating" or "biasing" an electrode of a synthesis cell thus means supplying a current or voltage to the electrode. The voltage may be supplied via a column line coupled to the synthesis cell or a reference voltage. The magnitude of the voltage may enable or inhibit a chemical reaction as the case may be.
[0018] The lateral (i.e., cross-shaped) arrangement of column and row lines enables a so-called "crossbar structure" in which specific electrodes and synthetic locations can be addressed by biasing column lines (e.g., corresponding to working electrodes - WE) and row lines (e.g., corresponding to counter electrodes - CE), rather than addressing each electrode individually. This can be conceptually compared to addressing the bit cells in a conventional crossbar solid-state memory cell (equivalent to the electrode surface at the synthetic aperture) by biasing word lines and bit lines.
[0019] By offsetting the row and column lines, the crossbar structure can effectively reduce the number of connections required to address the electrodes from one connection per electrode to a value proportional to the square root of the number of electrodes. Thus, improved scalability and area efficiency can be achieved.
[0020] In addition, the surface portions of the upper and lower electrodes exposed in each synthetic aperture can be capacitively coupled to each other to thereby provide the synthetic aperture with its own intrinsic capacitance, thereby allowing charge to be stored in the synthetic aperture for a certain amount of time. Therefore, after the external bias voltage is removed via the column and row lines, the bias on the synthetic aperture can be maintained to achieve the synthesis reaction without the need for, for example, external capacitors. As will be described in detail below, this enables a time-division multiplexed biasing scheme for parallel synthesis in multiple synthetic apertures.
[0021] The pore structure of the synthesis unit further provides advantages associated with the synthesis reaction itself. The synthesis hole can define a relatively small partial volume relative to the larger common volume of the molecular synthesis array located above the synthesis hole. Therefore, the electrical induction reaction conditions for the synthesis reaction can be at least partially limited in each corresponding synthesis hole. This can reduce the risk of crosstalk between adjacent synthesis holes. As a non-limiting and illustrative example, in the synthesis reaction in which the reaction rate depends on the proton concentration produced by the redox reaction in the reagent solution, the desired proton concentration can be locally realized in the partial volume of the synthesis hole by biasing the lower electrode and the upper electrode at the selected synthesis hole. Even if some protons (for example driven by increased proton concentration) may diffuse out from the selected synthesis hole, the proton concentration can also suddenly drop in the larger volume outside the synthesis hole. Therefore, the influence of the protons diffused outward from the (selected) synthesis unit on the reaction conditions in the adjacent (unselected) synthesis hole can be ignored.
[0022] Providing a selection transistor in each synthesis cell allows the synthesis cells to be selectively enabled with minimal risk of crosstalk, even if the synthesis cells are arranged relatively close to each other.
[0023] Relative spatial terms, such as "above", "below", "vertical" and "arranged on...", may be used herein to refer to a position or orientation within a reference frame of a molecular synthesis array. In particular, these terms may be understood relative to a bottom-up direction of the molecular synthesis array, i.e., a direction normal to (the main extension plane of) the substrate. Correspondingly, the term "horizontal" may be understood as a position or orientation transverse to the bottom-up direction, i.e., relative to / along (the main extension plane of) the substrate.
[0024] The row direction and the column direction are understood to be directions transverse (horizontal) to each other, each parallel to the substrate.
[0025] The phrase "column lines extend across row lines" or vice versa therefore means that the column lines extend over and across the row lines, or vice versa. In other words, the column lines are arranged to define an overlap with the row lines, as seen along a vertical direction (e.g., towards the substrate). Correspondingly, the phrase "at an intersection", such as "at an intersection between a row line and a column line", should be understood as a location where the row line defines an overlap with the column line, as seen along a vertical direction (e.g., towards the substrate).
[0026] The phrase "vertically separated" from the row lines thus means that the column lines and the row lines are physically and galvanically separated along the vertical direction. The same is true for the lower and upper electrodes of each synthesis unit.
[0027] The wording “embedded”, such as the upper electrode and the lower electrode “embedded in the insulating layer”, here means that the column lines and the row lines are surrounded by the insulating layer.
[0028] The hole of each synthesis unit may include an upper portion extending from an upper surface of the insulating layer to the upper electrode and exposing an upper surface portion of the upper electrode; and a lower portion extending from the upper electrode to the lower electrode.
[0029] Providing a synthetic hole with a lower hole portion and an upper hole portion allows the depth of the synthetic hole to be increased without increasing the vertical spacing between the upper electrode and the lower electrode. A deeper synthetic hole can help limit the reaction conditions to the selected synthetic hole. For example, when using a synthetic array, protons can be generated in the lower portion of the selected synthetic hole. Exposing the upper surface portion of the upper electrode by the upper hole portion allows the area of the upper surface portion of the upper electrode to increase relative to the area of the surface portion of the lower electrode. This can allow balancing the reactions occurring at the surface portion of the lower electrode and at the upper surface portion of the upper electrode. Assuming, for example, that the surface portion of the lower electrode and the surface portion of the upper electrode are configured as the working electrode and the counter electrode, respectively, the protons generated by the oxidation reaction at the working electrode can be consumed in the redox reaction at the counter electrode. This in turn can reduce the outward diffusion of protons, which may cause crosstalk between synthetic units.
[0030] The cross-sectional area of the upper portion of each hole may be greater than the cross-sectional area of the lower portion of the hole. More specifically, the upper surface portion of the upper electrode may be greater than the surface portion of the lower electrode.
[0031] Consistent with the above discussion, the upper surface portion of the upper electrode can thus cause protons generated at the surface portion of the lower electrode to be largely consumed by the upper surface portion of the upper electrode, thereby reducing the risk of protons escaping from the synthetic aperture.
[0032] The area of the exposed upper surface portion of the upper electrode may be at least twice the area of the exposed surface portion of the lower electrode. The area of the exposed upper surface portion of the upper electrode may be about three times the area of the exposed surface portion of the lower electrode.
[0033] This can ensure that the surface area of the upper surface portion of the upper electrode is sufficiently large relative to the surface area of the surface portion of the lower electrode.
[0034] The selection transistor of each synthesis unit can be a first selection transistor of a first conductivity type, and each synthesis unit can further include a second selection transistor, which is of an opposite second conductivity type and has a first terminal, a second terminal and a gate terminal, and the first terminal and the second terminal can form corresponding source terminals / drain terminals of the second selection transistor, wherein the gate terminal of each of the selection transistors can be coupled to a row line, the first terminal can be coupled to a column line, and the second terminal can be coupled to a lower electrode (in a first unit configuration), or wherein the gate terminal of each of the selection transistors can be coupled to a row line, the first terminal can be coupled to a column line, and the second terminal can be coupled to an upper electrode (in a second unit configuration).
[0035] In other words, the selection transistors may be complementary metal oxide semiconductors (CMOS). A pair of selection transistors with opposite conductivity types allows the synthetic aperture to be biased with both negative and positive polarity voltages by applying voltages above or below a (fixed) reference voltage via the column lines. For example, if the upper electrode (in the case of the first cell configuration) or the lower electrode (in the case of the second cell configuration) is connected to a ground level reference voltage, a positive polarity voltage (as seen from the lower electrode to the upper electrode) may be provided by applying a positive voltage to the column line, and a negative polarity voltage may be provided by applying a negative voltage to the column line.
[0036] Each lower electrode may be configured as a working electrode, and each upper electrode may be configured as a counter electrode.
[0037] Thus, in response to a positive (negative) voltage, the working electrode can act as a proton producing (consuming) electrode, and the counter electrode can act as a proton consuming (producing) electrode.
[0038] The vertical spacing between the lower electrode and the upper electrode of each synthesis unit can be smaller than the spacing of the synthesis holes. In other words, the vertical distance between the upper electrode and the lower electrode in the synthesis hole can be smaller than the horizontal distance between two adjacent synthesis holes.
[0039] The vertical spacing between the plurality of lower electrode lines and the plurality of upper electrode lines may be 40 to 300 nm, and the pitch of the synthetic apertures may be at least 40 nm.
[0040] According to a second aspect of the inventive concept, a molecular synthesis device is provided. The molecular synthesis device includes a molecular synthesis array according to the first aspect, and further includes an array controller, which is configured to implement synthesis in a selected synthesis unit among a plurality of synthesis units of the molecular synthesis array by applying a selection voltage to a row line coupled to the selected synthesis unit, and applying a synthesis voltage to a column line coupled to the selected synthesis unit. Therefore, the array controller can supply the synthesis voltage to the selected synthesis unit along the activated row line.
[0041] The array controller may be further configured to implement synthesis in a group of selected synthesis cells in parallel by applying a corresponding selection voltage pulse train to a row line coupled to each corresponding synthesis cell in the group of selected synthesis cells and applying a corresponding synthesis voltage pulse train to a column line coupled to each corresponding synthesis cell in the group of selected synthesis cells, wherein the selection voltage pulse train and the synthesis voltage pulse train are simultaneously applied to the molecular synthesis array in a time division multiplexed manner.
[0042] Due to the use of a crossbar array structure, a row line and a column line can be activated simultaneously for the selective addressing of a single synthetic aperture. By using a time-division multiplexing scheme as described above, a more time-efficient molecular synthesis process can be performed on a molecular synthesis device. More specifically, since the time of the voltage pulse can be much shorter than the reaction time (e.g., 1 ms versus 10 s), multiplexing can be performed through all upper and lower electrode lines associated with a group of selected synthetic units, which can work as effectively as if all selected synthetic units were activated at the same time. In order to facilitate the multiplexing method, it is necessary to store enough charge in a very short period of time to allow the reaction to continue to occur while multiplexing is performed through other electrode lines, which can be provided by the inherent capacitance of the synthetic aperture itself, as discussed above.
[0043] The molecular synthesis device may further include a cover, which is arranged on the molecular synthesis array and defines a synthesis compartment for accommodating a solution containing a synthesis reagent on the upper surface of the insulating layer, wherein the synthesis compartment can be connected to the synthesis holes of the plurality of synthesis units. Accordingly, the synthesis compartment and the synthesis hole of the molecular synthesis device can include a solution containing a synthesis reagent during use.
[0044] The molecular synthesis device may further include: a group of reagent compartments, each reagent compartment being configured to hold a reagent solution; a fluid channel arrangement, the fluid channel arrangement being connected between the group of reagent compartments and the synthesis compartment and being configured to transfer the reagent solution from each reagent compartment to the synthesis compartment; and a fluid controller, the fluid controller being configured to control the transfer of the reagent solution from the reagent compartment to the synthesis compartment.
[0045] According to a third aspect of the inventive concept, a data storage system is provided. The data storage system comprises a molecular synthesis device according to the second aspect and a memory controller, the memory controller being configured to receive an input data stream to be stored at a selected position in a synthesis array, and to enable the array controller to implement synthesis in a selected synthesis unit based on the input data stream.
[0046] According to a fourth aspect of the inventive concept, there is provided a method for implementing synthesis in a selected synthesis unit of a molecular synthesis array of a molecular synthesis device according to the second aspect. The method comprises: applying a selection voltage to a row line coupled to the selected synthesis unit, and applying a synthesis voltage to a column line coupled to the selected synthesis unit.
[0047] The effects and features of the second, third and fourth aspects of the present invention are largely similar to those described above in conjunction with the first aspect of the present invention. The embodiments mentioned with respect to the first aspect of the present invention are compatible with other aspects of the present invention to a large extent. In order to avoid excessive repetition, reference is made to the above. BRIEF DESCRIPTION OF THE DRAWINGS
[0048] The above and other aspects of the inventive concept will now be described in more detail with reference to the accompanying drawings showing variations of the inventive concept. The drawings should not be considered to limit the invention to the specific variations; rather they are used to explain and understand the inventive concept.
[0049] Figure 1A is a schematic circuit layout of a molecular synthesis array including a synthesis unit according to one embodiment.
[0050] Figure 1B is a schematic circuit layout of a molecular synthesis array including a synthesis unit according to another embodiment.
[0051] Figure 2A is a cross-sectional side view of a synthesis unit of a molecular synthesis array according to one embodiment.
[0052] Figure 2B yes Figure 2A Top view of the synthesis unit.
[0053] Figure 2C yes Figure 2A A cross-sectional perspective view of a synthesis unit.
[0054] Figure 3 is a schematic diagram of a molecular synthesis apparatus according to an embodiment.
[0055] Figure 4 is a schematic diagram of a data storage system according to an embodiment.
[0056] Figure 5AThis is a diagram for illustrating a writing scheme of a molecular synthesis device.
[0057] Figure 5B is a schematic diagram of the molecular synthesis array. DETAILED DESCRIPTION
[0058] The inventive concept will now be described more fully hereinafter with reference to the accompanying drawings, in which embodiments are shown. However, the inventive concept may be implemented in many different forms and should not be construed as limited to the variations set forth herein; rather, these variations are provided for thoroughness and completeness and to fully convey the scope of the inventive concept to the skilled person.
[0059] Now, reference will be made to FIGS. 1 to Figure 5B Embodiments of molecular synthesis arrays, molecular synthesis devices including molecular synthesis arrays, data storage systems including molecular synthesis devices, and methods for implementing synthesis in molecular synthesis devices are described. It should be noted that the relative sizes and shapes of different layers or components may not represent the physical implementation of the corresponding device. For example, for illustrative purposes, some structures and layers may be exaggerated in this article.
[0060] The inventive concept can be used for any application that utilizes in situ DNA synthesis and requires high density and therefore ultra-high throughput, such as DNA data storage, gene expression profiling, spatial transcriptomics, etc. In addition, the inventive concept can also be used to drive other electrochemical reactions, not only for DNA synthesis, but also for the synthesis of polymers and RNA.
[0061] In data storage applications, stable organic molecules (such as polymers, DNA or RNA) can be synthesized in a structured manner to form molecules that map to data symbols. Knowing the data encoding scheme employed during writing, i.e., the mapping between the data symbols and the building structure of the synthesized molecules, the written data symbols can be read out from the structure of the synthesized molecules accordingly, such as the sequence of monomers (for polymers) or the sequence of base pairs (for DNA or RNA). In other words, molecular synthesis arrays can be used to control the generation of oligonucleotide chains, which can be used to encode data similar to bits.
[0062] According to the inventive concept, a molecular synthesis array is provided, which comprises an array of synthesis units coupled to column lines and row lines, and each synthesis unit comprises a synthesis unit that limits corresponding synthesis positions. Reagents for synthesis can be supplied to the synthesis positions by valves and channels (such as microfluidic channels). Subsequently, by using a corresponding pair of column lines and row lines coupled to selected synthesis units to bias the upper electrode and the lower electrode of the synthesis unit, synthetic chemical reactions can be achieved. Hereinafter, reference will be mainly made to the solid phase DNA synthesis controlled by ion generation. However, it is envisioned that the molecular synthesis array may also be compatible with other synthesis reactions, in which the reaction rate may be controlled by the redox reaction of electrochemical induction.
[0063] The in-situ synthesis of DNA microarray is based on conventional solid phase DNA synthesis. In short, successive synthesis cycles are performed to add phosphoramidite nucleotides to growing oligonucleotide chains that are bound on the surface. Each synthesis cycle can be composed of the following four steps: phosphoramidite nucleotide coupling; end-capping; phosphate backbone oxidation; and deprotection of coupled nucleosides to allow the addition of the next phosphoramidite nucleotide. The locally controlled deprotection step (detritylation) enables the addition of nucleotides only at the desired position, and therefore allows the synthesis of multiple DNA chains in parallel.
[0064] On an electrode array (such as the molecular synthesis array of the present invention), the detritylation step can be induced electrochemically. Briefly, a synthesis site (i.e., a synthesis well) can be provided with a material containing a molecule known to release (e.g., as hydrogen ions H) upon oxidation. + The electrode is rinsed with a detritylation solution of a redox pair of protons (e.g., hydroquinone / benzoquinone, hydrogen / fluorine, hydrogen / chlorine, or any other redox pair in which the reaction is not diffusion limited (i.e., a redox reaction dominated by Butler-Volmer kinetics)). In the event that the next nucleotide addition is desired, an oxidation potential relative to the working electrode and the counter electrode at the synthesis site can be applied. The oxidation reaction occurring at the surface of the selected electrode causes the release of protons at the electrode surface at the synthesis site, which causes the local pH to drop, thereby inducing the removal of the DMT (dimethoxytrityl) protecting group of the phosphoramidite at the oligonucleotide chain bound to the surface. For example, the reaction rate v of the synthesis reaction can be linearly dependent on the power product of the reactant concentrations (e.g., v=k[H + ] s [Nucleoside + DMT] t , where [H + ] is the proton concentration, and [nucleoside+DMT] is the concentration of nucleosides with the DMT protecting group of the phosphoramidite). In a subsequent step, the next nucleotide can be added to the chain.
[0065] Figure 1AThe schematic diagram of the circuit layout of the molecular synthesis array 100 according to one embodiment is shown by way of example. The exemplary structure of the molecular synthesis array 100 is combined with FIG. 2A to FIG. 2C Further Description: In order to clearly illustrate the electrical connections of the molecular synthesis array 100, the placement and size of the components in the circuit system layout may be exaggerated and should not be considered as limiting the actual molecular synthesis array 100.
[0066] The molecular synthesis array 100 includes a plurality of column lines 102. For illustration purposes, the molecular synthesis array 100 is illustrated herein as having two column lines C1 and C2. However, it should be noted that the molecular synthesis array 100 may include any number of column lines. The plurality of column lines 102 extend in parallel along the column direction of the molecular synthesis array 100.
[0067] The molecular synthesis array 100 further includes a plurality of row lines 104. For demonstration purposes, the molecular synthesis array 100 is shown herein as having two row lines R1 and R2. However, the molecular synthesis array 100 may include any number of row lines. In the example shown, the molecular synthesis array 100 includes the same number of column lines and row lines (e.g., to define an array with a square layout). However, the molecular synthesis array 100 may include a different number of column lines and row lines (e.g., to define an array with a non-square rectangular layout). The plurality of row lines 104 extend in parallel along the row direction of the molecular synthesis array 100.
[0068] The row direction is transverse to the column direction. In the example shown, the row direction is perpendicular to the column direction. However, the row direction and the column direction may extend across each other at an angle other than a right angle (e.g., at a slightly inclined angle). Further, the row lines and the column lines are physically and electrically separated vertically.
[0069] The molecular synthesis array 100 further includes a plurality of synthesis cells 105. Each synthesis cell can be used as a synthesis location of the molecular synthesis array 100. Each synthesis cell is coupled to a corresponding pair of column lines and row lines. A synthesis cell can be selected by biasing the corresponding row and column lines. As an example, by applying a first voltage (e.g., a "synthesis voltage") to the first column line C1 and applying a second voltage (e.g., a "selection voltage") to the first row line R1, the synthesis cell C1-R1 can be selected. As shown in FIG. Figure 3 As further described, the voltage may be supplied by an array controller coupled to the row lines and column lines. Figure 5A and Figure 5B The addressing scheme is described in more detail.
[0070] Each synthesis unit includes a lower electrode 112 and an upper electrode 110. The lower electrode 112 can be configured as a working electrode, and the upper electrode 110 can be configured as a counter electrode of the corresponding synthesis unit. Each synthesis unit further includes a synthesis hole. The synthesis hole exposes a surface portion of the upper electrode and a surface portion of the lower electrode of the synthesis unit (at FIG. 2A to FIG. 2C further shown in ).
[0071] The synthesis holes of the plurality of synthesis units 105 may be arranged at regular intervals along the row direction and the column direction. The distance between two adjacent synthesis holes along the column direction or the row direction may be referred to as the pitch of the molecular synthesis array 100. The pitch of the molecular synthesis array 100 may correspond to the pitch of the column line and the row line. Figure 1A It is indicated that the pitch along the column direction and the pitch along the row direction may be the same, but it is envisaged that the array may exhibit different pitches along the column direction and the row direction.
[0072] Each synthesis cell further includes a single selection transistor 106 ("1T cell"). The selection transistor 106 is configured as a three-terminal selector device for the synthesis cell. The selection transistor 106 has a first terminal 114a, a second terminal 114b and a gate terminal 114c. The first terminal 114a and the second terminal 114b form respective source terminals / drain terminals of the selection transistor 106. In the example shown, the gate terminal 114c is coupled to a row line. Thus, the row line can be used as a selection line or word line to turn on the selection transistor 106 by applying a selection voltage. For example, for an n-type MOSFET, the selection voltage can be a positive voltage (e.g., a high logic level voltage) that exceeds the threshold voltage of the selection transistor 106. The first terminal 114a (i.e., the source or drain of the transistor) is coupled to a column line. Thus, the column line can be used as a bit line to supply the synthesis voltage to the synthesis cell. Figure 1A The synthesis unit in the embodiment has a so-called first configuration, and accordingly, the second terminal 114b of the selection transistor 106 is coupled to the lower electrode 112, while the upper electrode 110 is coupled to the reference voltage (V ref ).
[0073] In the example shown, the reference voltage is a reference voltage source 108 that can be switched between a first reference voltage level and a second reference voltage level. The first reference voltage level can be a ground voltage, and the second reference voltage level can be a positive reference voltage. In this way, both positive polarity voltages and negative polarity voltages can be applied to the synthesis unit. For example, by applying a positive voltage to the column line C2 and applying the first reference voltage level to the upper electrode 110, a positive polarity voltage (as seen from the lower electrode 112 to the upper electrode 110) can be provided. At the same time, by applying the second reference voltage level to the upper electrode 110 and applying a ground voltage (or another low level voltage less than the second reference voltage level) to the lower electrode 112, a negative polarity voltage (as seen from the lower electrode 112 to the upper electrode 110) can be provided.
[0074] Although Figure 1A A separate reference voltage source is shown for each synthesis cell 105, but the respective upper electrodes 110 of the synthesis cells may also be coupled to a common reference voltage. Thus, the common reference voltage may be simultaneously applied to the respective upper electrodes of a plurality of synthesis cells 105. For example, the upper electrodes may be formed by a common metal layer extending over the synthesis array 100, or by a plurality of metal lines extending, for example, in a row direction or a column direction.
[0075] The synthesis cell 105 may alternatively be arranged according to a so-called second cell configuration, in which the upper electrode 110 is coupled to the second terminal 114b of the select transistor 106 instead, and the lower electrode 112 is coupled to the reference voltage. The second cell configuration is schematically illustrated by the dashed lines in the synthesis cell coupled to the row line R1 and the column line C1. The description of the reference voltage above with reference to the first cell configuration applies correspondingly to the second cell configuration, except that the polarity of the voltage is reversed.
[0076] Figure 1B A schematic diagram of a circuit layout of a molecular synthesis array 100 according to another embodiment is shown by way of example.
[0077] The molecular synthesis array 100 has two column lines C1 and C2, two row lines R1 and R2, and four synthesis units.
[0078] and Figure 1A The molecular synthesis array 100 forms a control, Figure 1B Each synthesis unit 105 includes two selection transistors ("2T unit"). That is, a first selection transistor 106a of a first conductivity type (e.g., n-type) and a second selection transistor 106b of an opposite conductivity type (e.g., p-type). Therefore, the selector device 106 of each synthesis unit 105 can be a complementary metal oxide semiconductor (CMOS) transistor pair.
[0079] Each of the first select transistor 106a and the second select transistor 106b has a first terminal 114a, 114a', a second terminal 114b, 114b' and a gate terminal 114c, 114c'. The first terminal 114a, 114a' and the second terminal 114b, 114b' form the respective source terminal / drain terminal of the respective first select transistor 106a and the second select transistor 106b. In the illustrated example, the gate terminals 114c, 114c' of the first select transistor 106a and the second select transistor 106b are coupled to the row line. The first terminals 114a, 114a' of the first select transistor 106a and the second select transistor 106b are coupled to the column line. Thus, similar to Figure 1A In the embodiments, the row lines and column lines can be used as selection lines / word lines and bit lines, respectively. The second terminals 114b, 114b' of the first selection transistor 106a and the second selection transistor 106b are coupled to the lower electrode 112. The upper electrode 110 is coupled to a reference voltage in the form of a ground voltage. In other words, the potential of the upper electrode 110 is set to ground. More generally, the reference voltage can instead be a low (logic) level voltage or a negative power supply voltage (e.g., VSS) supplied by a reference voltage source. By having a first selection transistor 106a and a second selection transistor 106b of opposite conductivity types, both a positive voltage and a negative voltage can be supplied to the lower electrode 112, so that a positive polarity voltage or a negative polarity voltage can be applied to the synthesis unit. The upper electrodes 110 of multiple synthesis units 105 can be coupled to a common ground to simplify the circuit layout. Although Figure 1B A separate reference voltage (e.g., ground) is shown for each synthesis cell 105, but the respective upper electrodes 110 of the synthesis cells may also be coupled to a common reference voltage (e.g., common ground). For example, the upper electrode may be formed by a common metal layer extending over the synthesis array 100, or by a plurality of metal lines extending, for example, in a row direction or a column direction, the metal layer or the metal lines forming a common ground plane for the plurality of synthesis cells 105.
[0080] Although the illustrated example corresponds to a so-called first cell configuration, a so-called second configuration may also be used in a 2T cell, wherein the second terminals 114b, 114b' of the first and second select transistors 106a, 106b may be coupled to the upper electrode 110, and the lower electrode 112 may be coupled to a reference voltage (e.g., ground). The second cell configuration is schematically illustrated by the dashed lines in the composite cell coupled to the row line R1 and the column line C1.
[0081] Figure 2A is a cross-sectional side view of a synthesis hole 223 of a synthesis unit 200 of a molecular synthesis array 100 according to one embodiment. Figure 2B is a top view of the same synthesis unit 200. Figure 2C 2 is a three-dimensional cross-sectional view through the same synthesis unit 200, wherein another synthesis hole 223' of an adjacent synthesis unit can also be seen. FIG. 2A to FIG. 2C The synthesis aperture 223 of the synthesis unit 200 shown generally represents Figure 1A to Figure 1B A synthetic aperture of any one of the plurality of synthetic units 105 of the array 100 is shown.
[0082] As described above, the combining unit 200 is coupled to a corresponding pair of column and row lines. FIG. 2A to FIG. 2C Column and row lines are not shown in an individualized manner, but are considered to form part of the schematically shown substrate layer 212, which includes, for example, a semiconductor substrate on which CMOS devices and interconnect structures are formed. The column and row lines can be formed of any material suitable for forming CMOS interconnect structures, such as copper, aluminum, tungsten, as some non-limiting examples.
[0083] The synthesis unit 200 includes an upper electrode 206 and a lower electrode 226. The upper electrode 206 and the lower electrode 226 can be formed of any material suitable as an electrode material. Examples include, but are not limited to, platinum, gold, and ruthenium. The lower electrode 226 can be configured as a working electrode, and the upper electrode 206 can be configured as a counter electrode of the synthesis hole 223.
[0084] The lower electrode 226 and the upper electrode 206 of the synthesis unit 200 are embedded in the insulating layer 202. The insulating layer 202 can be a composite stack as shown. In other words, the insulating layer 202 can include a plurality of insulating layers 204, 208, 210 made of one or more insulating materials. For example, the insulating layer 202 can include one or more layers of silicon oxide and / or silicon nitride. In particular, the lower electrode 226 and the upper electrode 206 can be completely encapsulated by the insulating layer 202 (except for the exposed surface portions of the upper electrode 206 and the lower electrode 226 in the synthesis hole 223, as explained below). The upper electrode 206 and the lower electrode 226 are vertically separated from each other by a certain distance h1. A portion 208 of the insulating layer 202 is therefore arranged between the upper electrode 206 and the lower electrode 226 to separate them from each other. The insulating layer 202 further includes an upper portion 204, which is arranged on and covers the upper electrode 206. The upper portion 204 of the insulating layer 202 has a thickness indicated by h2, such as Figure 2C As seen in.
[0085] The synthetic aperture 223 extends from an upper surface 225 of the insulating layer 202 through the insulating layer 202 and through the upper electrode 206 to the lower electrode 226. The synthetic aperture 223 thereby exposes an upper surface portion 214 of the upper electrode 206 and an upper surface portion 220 of the lower electrode 226. The surface portion 220 of the lower electrode 226 forms the bottommost surface of the synthetic aperture 223. The exposed surface portions 214, 220 of the upper electrode 206 and the lower electrode 226 may serve as electrode surfaces of the synthetic aperture 223 in question.
[0086] The synthetic hole can be a circular hole, such as Figure 2B However, as the skilled person will appreciate, the synthetic aperture may also have other shapes, such as a polygon or an ellipse.
[0087] As shown, the synthetic aperture 223 may include an upper portion 224 and a lower portion 222. The upper portion 224 and the lower portion 222 of the synthetic aperture 223 may be centered relative to a common central axis as viewed along a vertical direction (e.g., toward the substrate). The upper portion 224 extends from the upper surface 225 of the insulating layer 202 to the upper electrode 206 and exposes an upper surface portion 214 of the upper electrode 206. The lower portion 222 of the synthetic aperture 223 extends from the upper electrode 206 and passes through the upper electrode to the lower electrode 226. As shown in Figure 2B As seen in FIG. 2 , the upper electrode surface 214 circumferentially surrounds the topmost portion of the lower portion 222 of the synthetic aperture 223 formed through the upper electrode 206 (i.e., the hole in the upper electrode 206). FIG. 2A to FIG. 2C As shown, the hole / top-most portion of the lower portion 222 also exposes a side surface portion 218 of the upper electrode 206 (surrounding the hole in the upper electrode 206 ).
[0088] The lower portion 222 of the synthetic hole 223 has a first diameter as indicated by the label d1. The upper portion 224 of the synthetic hole 223 has a second diameter as indicated by the label d2. FIG. 2A to FIG. 2B As can be seen in , d2 is greater than d1, so that the cross-sectional area of the upper portion 224 (as seen along the vertical direction) exceeds the cross-sectional area of the lower portion 222. In particular, the area of the exposed upper surface portion 214 of the upper electrode 206 can be greater than the area of the exposed surface portion 220 of the lower electrode 226. For example, the area of the exposed upper surface portion 214 of the upper electrode 206 can be at least twice the area of the exposed surface portion 220 of the lower electrode 226, such as about 3 times.
[0089] In any case, the vertical spacing between the lower electrode 226 and the upper electrode 206 may be smaller than the spacing between the synthetic aperture 200 and the adjacent synthetic aperture 200' (eg, Figure 2CAs seen in (i.e., the pitch of the molecular synthetic apertures 223), since this improves the selectivity of the addressing scheme. As a non-limiting example of dimensions associated with the synthetic apertures 223, h1 can be 40 to 300 nm and h2 can be 40 to 300 nm. The pitch p of the synthetic apertures can, for example, be at least twice that of h1.
[0090] As an alternative to having upper and lower portions 224, 222 of synthetic aperture 223 having different diameters, it is contemplated that the width of synthetic aperture 223 may be the same size along the depth of synthetic aperture 223. In this case, side surface portions 218 of upper electrode 206 surrounding the hole through upper electrode 206 may be the only exposed electrode surface of upper electrode 206.
[0091] As above combined Figure 1A As described, the synthesis unit 200 further includes a selection transistor 106. Alternatively, as in combination Figure 1B As depicted, the synthesis unit 200 may include a first select transistor 106a and a second select transistor 106b. The select transistor(s) 106 / 106a-b may be included in the substrate layer 212 as may the column and row lines. The second terminal 114b of the select transistor 116 or the second terminals 114b and 114b' of the select transistors 106a, 106b may be coupled to the lower electrode 226 via an interconnect structure, such as including a first interconnect portion 230 extending from the terminal 114b / 114b, 114b' to a second interconnect portion in the form of a metal via 228 coupling the lower electrode 226 to the first interconnect portion 230. Provided that the select transistor(s) 106 / 106a-b are formed within the footprint of the lower electrode 226, the first interconnect portion 230 may simply be a metal contact adjacent to the second terminal 114b / 114b, 114b' of the select transistor(s). However, the select transistor(s) 106 / 106a - b may be more generally shifted relative to the lower electrode 226 , wherein the first interconnect portion 230 may include a combination of horizontal and vertical wiring resources extending to a location below the lower electrode 226 and the metal vias 228 .
[0092] As above combined Figure 1A and Figure 1B As described, the upper electrode 206 may be formed of a single metal layer common to all the synthesis units 105. Alternatively, the upper electrode 206 may be formed of metal lines extending in the row direction and / or column direction of the synthesis units 105, thereby connecting the upper electrodes 206 together along the rows and / or columns.
[0093] Figure 3 Schematic diagram of a molecular synthesis device 300. The molecular synthesis device 300 includes a combination of Figures 1A to 2C The molecular synthesis array 100 of any one of the described embodiments. The molecular synthesis device 300 further includes an array controller 302. The array controller 302 is capable of performing synthesis in a selected synthesis unit among a plurality of synthesis units of the molecular synthesis array 100. The array controller 302 performs synthesis by (as described above in conjunction with Figure 1A to Figure 1B The array controller 302 may be configured to provide a plurality of circuits for the synthesis of the plurality of cells. ...
[0094] The array controller 302 may be further configured to implement synthesis in parallel in a group of selected synthesis units. Parallel synthesis may be performed by supplying a corresponding voltage pulse train to each synthesis unit in the group of selected synthesis units, wherein the voltage pulse trains are simultaneously applied to the molecular synthesis array 100 in a time division multiplexing manner. Figure 5A and Figure 5B An example of how the synthesis can be performed in a time division multiplexed manner is further described.
[0095] The molecular synthesis device 300 may further include a cover, which is arranged on the molecular synthesis array 100 to define a synthesis compartment or fluid pool 310 on the upper surface of the insulating layer for receiving and accommodating a solution (i.e., a reagent solution) containing a synthesis reagent. The synthesis compartment 310 may be connected to a plurality of synthesis holes. Accordingly, the solution received in the synthesis compartment 310 may flow into and fill the synthesis hole.
[0096] The molecular synthesis apparatus 300 may further include a set of reagent compartments 306A-C. Each reagent compartment in the set of reagent compartments 306A-C may be configured to hold a reagent solution. Different reagent compartments in the set of reagent compartments 306A-C may hold different reagent solutions, such as a reagent compartment containing a solution of different phosphoramidite nucleotides, and a reagent compartment containing a detritylation solution including a redox pair, to facilitate proton release in the selected synthesis pore and thus enable a synthesis reaction therein.
[0097] The molecular synthesis device 300 may further include a fluid channel 308A-C arrangement that is coupled between the set of reagent compartments 306A-C and the synthesis compartment 310 and is configured to transfer reagent solutions from each reagent compartment to the synthesis compartment 310. The fluid channel may be, for example, a microfluidic channel. Additional fluid channels may be present to manage the flow of reagent solutions within the molecular synthesis device 300.
[0098] The molecular synthesis device 300 may further include a fluid controller 304. The fluid controller 304 may be configured to control the transfer of reagent solutions from the reagent compartments 306A-C to the synthesis compartment 310. The fluid controller 304 may be, for example, a microfluidic controller. The fluid controller 304 may control the flow of the reagent solution using techniques known per se in the art (e.g., by controlling valves arranged along the fluid channels 308A-C).
[0099] The molecular synthesis device 300 can be configured to enable the use of solid phase DNA synthesis to synthesize oligonucleotides bound to the surface portion of the lower electrode of the synthetic hole of the synthesis array 100, wherein the molecular synthesis device 300 can be configured to achieve synthesis in the selected synthesis unit (or in a group of selected synthesis units using time division multiplexing) by applying a voltage to the synthetic hole of the (multiple) selected synthesis unit via the column lines and row lines coupled to the (multiple) selected synthesis unit to cause the deprotection of the protected nucleosides of the oligonucleotide chain bound to the surface portion of the lower electrode of the (multiple) selected synthesis unit. Thus, the nucleotides in the reagent solution can be added to the oligonucleotide chain. As described above, the applied voltage can induce the oxidation reaction of the redox pair in the reagent solution, so that the protons can be released at the electrode surface and deprotection is achieved (for example, the protecting group of the oligonucleotide chain is removed). This process can be repeated to add nucleotides to the oligonucleotide chain in sequence. The type of nucleotides added can be varied by changing the reagent solution containing the desired type of nucleotides, such as adenine, cytosine, thymine, or guanine (A, C, T, G).
[0100] In addition to inducing deprotection by proton generation (which means a voltage with positive polarity on the lower electrode (working electrode) and the upper electrode (counter electrode) of the selected synthetic pore) to enable the addition of nucleotides to the oligonucleotide chain, a negative polarity voltage can be applied to enable the grafting process. Grafting refers to the process of functionalizing the working electrode for synthesis, that is, attaching one or more anchor molecules (such as diazo compounds) to the lower electrode, on which the (corresponding) oligonucleotide chain can be synthesized. Like nucleotide addition, grafting can be selectively achieved by applying a voltage of negative polarity on the lower electrode and the upper electrode of the selected synthetic pore. However, it is considered that, alternatively, grafting can be achieved non-selectively (that is, in all synthetic pores of the synthetic array) as an initialization step before the (selective) sequential oligonucleotides in the synthetic pore. As can be understood, the amplitude of the positive polarity voltage (for deprotection) and the amplitude of the negative polarity voltage (for grafting) can be different.
[0101] Figure 44 is a schematic diagram of a data storage system 400. The data storage system 400 includes, for example, Figure 3 The described molecular synthesis device 300. The data storage system 400 further includes a memory controller 402. The memory controller 402 is configured to receive an input data stream, which is to be stored at a selected position in the molecular synthesis array of the molecular synthesis device 300. The memory controller 402 can be configured to enable the fluid controller 304 to supply appropriate reagent solutions to the synthesis array 100 in response to the input data stream. The memory controller 402 can be further configured to enable the array controller of the molecular synthesis device 300 to perform synthesis in the selected synthesis unit based on the input data stream. Therefore, the data storage system 400 can therefore allow data to be stored in the molecular synthesis device 300 by molecular synthesis.
[0102] The memory controller 402 may be configured to map received data symbols of an input data stream to corresponding nucleotides or corresponding nucleotide sequences. For example, using four nucleotides A, C, T, and G, data symbols may be stored in a quaternary system. In other words, the memory controller 402 may convert the data symbols of the input data stream from a binary format to a "polymer" domain, where the input data stream is represented as a polymer sequence. The memory controller 402 may thereafter synthesize the polymer sequence in one or more selected synthetic apertures.
[0103] Figure 5A is demonstrated in a molecular synthesis device (such as the above combined Figure 3 A diagram of a scheme for implementing synthesis in one or more selected synthesis units of the described molecular synthesis device 300). Figure 5B is a schematic diagram of an example of a molecular synthesis array having four column lines C1 to C4, four row lines R1 to R4, and 16 synthesis units (shown as circles) coupled to each pair of column and row lines.
[0104] In the simplest case, in which only a single synthesis cell is to be addressed (i.e., data is to be written therein), a single activation pulse having a length sufficient to complete the reaction may be applied to the corresponding column and row lines. When activating a synthesis cell, the activation pulse (i.e., a voltage pulse) is such that a positive or negative bias is applied to the synthesis cell, depending on which reaction is to be performed (e.g., deprotection or grafting). Thus, the polarity of the activation pulse applied to the lower and upper electrodes of the selected synthesis cell may be a positive potential or a negative potential. The row and / or column lines coupled to unselected synthesis cells may be left suspended (e.g., disconnected from drive by the drive circuitry from the array controller).
[0105] As described above, synthesis reactions can be achieved in parallel in a group of synthesis cells by applying activation / voltage pulse trains to the synthesis array in a time-division multiplexed manner.
[0106] Now refer to Figure 5A and Figure 5B and simultaneously at the intersections of R1-C2, R1-C4, R2-C1 and R2-C3 (e.g. Figure 5B This approach is described using an example of implementing synthesis in . Figure 5A The first cycle of multiple pulse trains is shown. Each pulse train corresponds to a row line and a column line. As described above, the pulses represent the activation of individual row lines and column lines, rather than applying actual potentials, because, depending on the motivation, a positive bias or a negative bias can be applied when activating the synthesis unit. The corresponding "activation pulses" applied to rows R1-R4 and columns C1-C4 can therefore be referred to as row address strobe pulses and column address strobe pulses, respectively. The time length of the first cycle can correspond to the time when the inherent capacitance of each synthesis unit (even without the application of external bias) can maintain sufficient charge to allow the synthesis reaction to continue. The first cycle of the activation pulse train can be repeated until the synthesis reaction in the synthesis hole is completed.
[0107] The first cycle is divided into four time periods. Each time period corresponds to the time of each pulse. ON Indicates the pulse length.
[0108] In the first time period, an activation pulse is applied to the first row line R1. In addition, an activation pulse is applied to the second column line C2 and the fourth column line C4. Therefore, the synthesis units R1-C2 and R1-C4 are activated for a period of time t ON Thereafter, the first row line R1 and the second and fourth column lines C2 and C4 are deactivated for the remainder of the first cycle.
[0109] In the second time period, an activation pulse is applied to the second row line R2. In addition, an activation pulse is applied to the first column line C1 and the third column line C3. Therefore, the synthesis units R2-C1 and R2-C3 are activated for a period of time t ON , after which they were deactivated.
[0110] In the third and fourth time periods, activation pulses are applied to the third and fourth row lines R3 and R4, respectively. However, since no column lines are activated, these pulse trains do not result in any activated synthesis cells.
[0111] As described above, the train pulse cycles presented herein may be repeated such that in subsequent time periods, synthetic apertures R1 - C2 and R1 - C4 are activated again, and so on.
[0112] By this example, it has been shown how a plurality of synthesis units can be activated simultaneously by applying an activation pulse train. ON , more synthesis units can be enabled at the same time.
[0113] Additionally, variations to the disclosed variations can be understood and effected by the skilled artisan in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.
Claims
1. A molecular synthesis array (100), comprising: substrate; an insulating layer (202), the insulating layer being arranged on the substrate; A plurality of column lines (102) and a plurality of row lines (104), wherein the plurality of column lines extend in parallel along the column direction of the molecular synthesis array (100), and the plurality of row lines extend in parallel along the row direction of the molecular synthesis array (100), wherein the column lines (102) are vertically separated from the row lines (104) and extend transversely to the row lines (104); A plurality of synthesis units (105), wherein each unit (200) is coupled to a corresponding pair of column and row lines and comprises: a lower electrode (226) and an upper electrode (206), the lower electrode and the upper electrode being vertically separated from each other and embedded in the insulating layer (202), a synthetic hole (223) extending from an upper surface (225) of the insulating layer (202), through the insulating layer (202) and through the upper electrode (206) to the lower electrode (226), wherein the hole (223) exposes a surface portion (214) of the upper electrode (206) and a surface portion (220) of the lower electrode (226), and a select transistor (106) having a first terminal (114a), a second terminal (114b) and a gate terminal (114c), the first terminal and the second terminal (114a, 114b) forming respective source / drain terminals of the select transistor (106), wherein the gate terminal (114c) is coupled to the row line, the first terminal (114a) is coupled to the column line, the second terminal (114b) is coupled to the lower electrode (226), and the upper electrode (206) is coupled to a reference voltage, or The gate terminal (114c) is coupled to the row line, the first terminal (114a) is coupled to the column line, the second terminal (114b) is coupled to the upper electrode (206), and the lower electrode (226) is coupled to a reference voltage.
2. The molecular synthesis array (100) according to claim 1, wherein: The hole (226) of each synthesis unit (200) includes: an upper portion (224) extending from the upper surface (225) of the insulating layer (202) to the upper electrode (206) and exposing an upper surface portion (214) of the upper electrode (206); and a lower portion (222) extending from the upper electrode (206) to the lower electrode (226).
3. The molecular synthesis array (100) according to claim 2, wherein: The cross-sectional area of the upper portion (224) of each hole (223) is greater than the cross-sectional area of the lower portion (222) of the hole (223).
4. The molecular synthesis array (100) according to claim 2 or 3, wherein: The area of the exposed upper surface portion (214) of the upper electrode (206) is at least twice the area of the exposed surface portion (220) of the lower electrode (226).
5. The molecular synthesis array (100) according to any one of claims 1 to 4, wherein: The transistor (106) of each synthesis unit (200) is a first selection transistor (106a) of a first conductivity type, and each synthesis unit (200) further includes a second selection transistor (106b) of a second opposite conductivity type and having a first terminal (114a'), a second terminal (114b') and a gate terminal (114c'), the first terminal and the second terminal (114a', 114b') forming respective source terminals / drain terminals of the second selection transistor (106b), wherein the gate terminal (114c, 114c') of each of the select transistors (106a, 106b) is coupled to the row line, the first terminal (114a, 114a') is coupled to the column line, and the second terminal (114b, 114b') is coupled to the lower electrode (226), or wherein a gate terminal (114c, 114c') of each of the selection transistors (106a, 106b) is coupled to the row line, the first terminal (114a, 114a') is coupled to the column line, and the second terminal (114b, 114b') is coupled to the upper electrode (206).
6. The molecular synthesis array (100) according to any one of the preceding claims, wherein: Each lower electrode (226) is configured as a working electrode, and each upper electrode (206) is configured as a counter electrode.
7. The molecular synthesis array (100) according to any one of the preceding claims, wherein: The vertical spacing between the lower electrode (226) and the upper electrode (206) of each synthesis unit (200) is smaller than the spacing of the synthesis holes (223).
8. The molecular synthesis array (100) according to any one of the preceding claims, wherein: The vertical spacing between the lower electrode (226) and the upper electrode (206) of each synthesis unit (200) is 40nm to 300nm, and the pitch of the synthesis holes (223) is at least 40nm.
9. A molecular synthesis device (300), comprising a molecular synthesis array (100) according to any one of the preceding claims, and further comprising an array controller (302), the array controller being configured to implement synthesis in a selected synthesis unit among a plurality of synthesis units of the molecular synthesis array (100) by the following steps: A select voltage is applied to a row line coupled to the selected synthesizing cell, and a synthesized voltage is applied to a column line coupled to the selected synthesizing cell.
10. The molecular synthesis device (300) according to claim 9, wherein: The array controller (302) is further configured to implement synthesis in a group of selected synthesis cells in parallel by applying a corresponding selection voltage pulse train to the row line coupled to each corresponding synthesis cell in the group of selected synthesis cells and applying a corresponding synthesis voltage pulse train to the column line coupled to each corresponding synthesis cell in the group of selected synthesis cells, wherein the selection voltage pulse train and the synthesis voltage pulse train are simultaneously applied to the molecular synthesis array (100) in a time division multiplexing manner.
11. The molecular synthesis device (300) according to claim 9 or 10, further comprising a cover, which is arranged on the molecular synthesis array (100) and defines a synthesis compartment (310) for accommodating a solution containing a synthesis reagent on the upper surface of the insulating layer, wherein: The synthesis compartment (310) is connected to the synthesis holes of the plurality of synthesis units.
12. The molecular synthesis device (300) according to claim 11, further comprising: a set of reagent compartments (306A-C), each reagent compartment being configured to hold a reagent solution; a fluid channel arrangement (308A-C) coupled between the set of reagent compartments (306A-C) and the synthesis compartment (310) and configured to transfer reagent solution from each reagent compartment (306A-C) to the synthesis compartment (310); and A fluid controller (304) configured to control the transfer of the reagent solutions from the reagent compartments (306A-C) to the synthesis compartment (310).
13. A data storage system (400), comprising a molecular synthesis device (300) according to any one of claims 9 to 12 and a memory controller (402), the memory controller being configured to receive an input data stream to be stored at a selected position in the synthesis array and to enable the array controller (302) to implement synthesis in a selected synthesis unit based on the input data stream.
14. A method for realizing synthesis in a selected synthesis unit of a molecular synthesis array of a molecular synthesis device (300) according to any one of claims 9 to 13, the method comprising: A select voltage is applied to the row line coupled to the selected synthesizing cell, and a synthesized voltage is applied to the column line coupled to the selected synthesizing cell.