Molecular synthesis array

Abstract

According to one aspect of the present invention, a molecular synthesis array (100, 100') is provided, the molecular synthesis array comprising: a substrate (208, 208'); an insulating layer (202, 202') disposed on the substrate (208, 208'); a plurality of lower electrode lines (104) and a plurality of upper electrode lines (102), the plurality of lower electrode lines extending parallel to each other along the column direction of the molecular synthesis array (100, 100'), the plurality of upper electrode lines extending parallel to each other along the row direction of the molecular synthesis array (100, 100'), wherein the upper electrode lines (102) are vertically separated from the lower electrode lines (210, 210') and extend across the lower electrode lines (104), and wherein the lower electrode lines and the upper electrode lines... (210, 210', 204, 204') are embedded in the insulating layer (202, 202'); and a plurality of composite holes (106) wherein each hole (200, 200') is formed at the intersection between the lower electrode line (210, 210') and the upper electrode line (204, 204'), and extends from the upper surface (226) of the insulating layer (202, 202'), through the insulating layer (202, 202') and through the upper electrode line (204, 204') to the lower electrode line (210, 210'), and exposes the electrode surface portions (222, 222') of the upper electrode line (204, 204') and the electrode surface portions (216, 216') of the lower electrode line (210, 210').

Description

Technical Field

[0001] This invention relates to a molecular synthesis array. It further relates to a molecular synthesis apparatus, a data storage system including the molecular synthesis apparatus, and a method for performing synthesis within the molecular synthesis apparatus. Background Technology

[0002] DNA (deoxyribonucleic acid) chips provide an array of nucleic acid strands fixed at defined sites on a solid surface. DNA chips allow for high-throughput electrochemical synthesis of DNA and have become a core technology in bioanalysis and biomedical diagnostics. Recently, in addition to traditional gene expression experiments, DNA microarrays have become powerful tools in many other research fields, such as for genome assembly, DNA origami, or as a data storage platform.

[0003] DNA chips can include electrode arrays that provide electrochemically controlled in-situ synthesis of different oligonucleotides at defined sites within the array. Advances in microfabrication techniques have enabled the scaling of electrodes, raising the potential for such arrays to allow for high-density and high-throughput DNA synthesis. While arrays for DNA synthesis have been mentioned above, this technology is not limited to DNA synthesis but can more generally be used for the synthesis of organic molecules such as polymers, DNA, or ribonucleic acid (RNA).

[0004] To date, microarrays for molecular synthesis typically rely on a structure in which each electrode (and therefore each synthesis site) is addressed individually. While this can facilitate selective addressing of synthesis sites, it makes scaling more challenging because increasing the number of electrodes complicates the wiring and also because the area required for wiring limits the electrode density. This can effectively limit the density of synthesis sites that can be achieved in an array. Summary of the Invention

[0005] In view of the foregoing, it is desirable to provide a molecular synthesis array capable of realizing a relatively large number of synthesis sites (i.e., high-density synthesis sites) in a relatively small region, for example, to facilitate the storage of large amounts of data in the array. Simultaneously, it is desirable to be able to selectively address individual synthesis sites to provide individual control over the synthesis reaction at each synthesis site (i.e., avoiding activation of adjacent synthesis sites). The purpose of this inventive concept is to address these needs. Further and alternative objectives may be understood from the following description.

[0006] According to a first aspect of the present invention, a molecular synthesis array is provided. The molecular synthesis array includes:

[0007] A substrate; an insulating layer disposed on the substrate; a plurality of lower electrode lines and a plurality of upper electrode lines extending parallel to each other along the column direction of a molecular synthesis array and extending parallel to each other along the row direction of the molecular synthesis array, wherein the upper electrode lines are vertically separated from the lower electrode lines and extend across the lower electrode lines, and wherein the lower electrode lines and upper electrode lines are embedded in the insulating layer; and a plurality of synthesis holes, wherein each hole is formed at the intersection between the lower electrode lines and the upper electrode lines and extends from the upper surface of the insulating layer, through the insulating layer and through the upper electrode lines to the lower electrode lines, and exposes the electrode surface portions of the upper electrode lines and the lower electrode lines.

[0008] The molecular synthesis array of the first aspect of the present invention can achieve many advantages:

[0009] (i) Increase the feasibility of area-efficient synthesis arrays with a large number of synthesis sites.

[0010] (ii) The hole structure at the synthesis location reduces the risk of crosstalk between adjacent synthesis holes.

[0011] (iii) Due to the reduced need for external selector devices (e.g., transistors) or capacitors (since the potential in the synthetic aperture itself can be used instead), the complexity during manufacturing is lower, and

[0012] (iv) The number of required electrode connections is scaled proportionally to the square root of the number of electrodes, rather than proportionally to the number of electrodes as in an array addressed one by one for each electrode (and therefore each synthesis location).

[0013] These advantages can be better and more fully understood from the following.

[0014] Based on the molecular synthesis array, an array of synthesis pores can be defined, wherein each synthesis pore can define a corresponding synthesis location (i.e., a synthesis point or synthesis unit), that is, the location of the molecular synthesis reaction can be achieved by electrically activating electrode lines crossing at the synthesis pores in the array. More specifically, the molecular synthesis array and its synthesis pores can be supplied with a molecular synthesis medium, such as a liquid solution containing reagents for the synthesis reaction, during use.

[0015] The electrode surfaces exposed at each synthesis well by the upper and lower electrode lines can be configured to control the reaction conditions at the corresponding synthesis well. The electrode surface at each synthesis well can be configured to initiate or inhibit a chemical reaction in the molecular synthesis medium in response to activation. The molecular synthesis medium (and any reagents supplied to the synthesis well) of each synthesis well can be configured such that a chemical reaction will be inhibited (i.e., will not occur) unless the associated electrode is activated. Alternatively, the molecular synthesis medium of each synthesis well can be configured such that a chemical reaction will be initiated (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 initiate or inhibit the reaction upon activation.

[0016] "Activating" or "biasing" an electrode thus means supplying current or voltage to the electrode via the lower and / or upper electrode lines. The magnitude of the voltage can be adjusted to either enable or inhibit a chemical reaction.

[0017] The cross arrangement of the lower and upper electrode lines achieves a so-called "crossbar structure," where specific electrodes and synthesis locations can be addressed by biasing the lower electrode (column) line (e.g., corresponding to the working electrode - WE) and the upper electrode (row) line (e.g., corresponding to the reverse electrode - CE), rather than addressing each electrode individually. This can be conceptually compared to addressing bit cells (equivalent to the electrode surfaces at synthesis vias) in conventional crossbar solid-state memory cells by biasing word lines and bit lines.

[0018] By biasing rows and columns (i.e., upper and lower electrode lines), the crossbar structure can effectively reduce the number of connections required for addressing electrodes from one connection per electrode to a value proportional to the square root of the number of electrodes. Therefore, improved scalability and area efficiency can be achieved.

[0019] Furthermore, forming a synthesis hole at the intersection of the lower and upper electrode lines allows the synthesis hole to expose the electrode surfaces of both the lower and upper electrode lines without requiring separate electrodes or additional wiring. Therefore, a compact and simple synthesis configuration can be achieved.

[0020] Furthermore, the exposed electrode surfaces in each synthesis well can be capacitively coupled to each other, thereby providing the synthesis well with its own inherent capacitance, allowing charge to be stored in the synthesis well for a certain period of time. Therefore, after removing the external bias voltage via the lower and upper electrode lines, the bias on the synthesis well 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 multiplexing bias scheme for parallel synthesis in multiple synthesis wells.

[0021] The arrangement of the synthesized vias at the intersection between the upper and lower electrode lines further allows the electrode surface portions to be arranged relatively close to each other (along the vertical direction normal to the main extension plane of the substrate) compared to the distance to adjacent synthesized vias (along the horizontal direction parallel to the main extension plane of the substrate). This reduces the risk of crosstalk between synthesized vias due to electrical leakage between them, since the path of lowest resistance will pass through the biased synthesized via itself.

[0022] The pore structure at the synthesis site further provides advantages associated with the synthesis reaction itself. The synthesis pores can define a relatively small partial volume relative to the larger common volume of the molecular synthesis array located above the synthesis pores. Therefore, the electro-induced reaction conditions used for the synthesis reaction can be at least partially confined within each respective synthesis pore. This reduces the risk of crosstalk between adjacent synthesis pores. As a non-limiting and illustrative example, in a synthesis reaction where the reaction rate depends on the proton concentration generated by a redox reaction in the reagent solution, the desired proton concentration can be locally achieved within a partial volume of the selected synthesis pore by biasing the lower and upper electrode lines that intersect at the selected synthesis pore. Even if some protons (e.g., driven by an increased proton concentration) may diffuse out of the selected synthesis pore, the proton concentration can abruptly decrease in a larger volume outside the synthesis pore. Therefore, the effect of protons diffusing outward from the (selected) synthesis pore on the reaction conditions in adjacent (unselected) synthesis pores can be negligible.

[0023] Furthermore, during the use of the molecular synthesis array, a voltage-current exponential correlation (so-called) similar to that of a Schottky diode can be obtained between the (metal) electrode surface of the lower electrode line in the synthesis hole and the reagent solution (e.g., a solution containing an active redox substance). This current relationship (exponentially correlated with the applied voltage) can be used as a selector device for the molecular synthesis array. Therefore, the need for an external transistor-based selector device can be eliminated. More precisely, and as those skilled in the art will understand, although the current relationship is similar to that of a Schottky diode, it is not due to the metal-semiconductor junction, but rather to the nonlinear charge-transfer resistance between the electrode and the reagent solution, which arises in redox reactions described by Butler-Volmer kinetics.

[0024] Relative spatial terms such as “above,” “below,” “vertical,” “arranged on,” and “middle” are used herein to refer to the position or orientation within the frame of reference of the molecular synthesis array. Specifically, these terms can be understood relative to the bottom-up direction of the molecular synthesis array (i.e., the normal direction of the substrate (the main extension plane)). Correspondingly, the term “horizontal” can be understood as a position or orientation transverse to the bottom-up direction, i.e., relative to / along the substrate (the main extension plane).

[0025] The row and column directions should be understood as mutually transverse (horizontal) directions, each parallel to the substrate.

[0026] The phrase "the upper electrode line extends across the lower electrode line" therefore means that the upper electrode line extends above and across the lower electrode line. In other words, the upper electrode line is arranged to define the overlap with the lower electrode line, as seen along the vertical direction (e.g., towards the substrate). Correspondingly, the phrase "at the intersection," such as "at the intersection between the lower and upper electrode lines," should be understood as the lower and upper electrode lines defining the position of the overlap, as seen along the vertical direction (e.g., towards the substrate).

[0027] The phrase "vertically separated" between the upper and lower electrode lines therefore implies that the upper and lower electrode lines are physically and electrically separated along the vertical direction.

[0028] The term "embedded" means that the lower and upper electrode wires are "embedded in the insulating layer," implying that the lower and upper electrode wires are surrounded by the insulating layer.

[0029] Each of the plurality of synthetic vias may include: an upper portion extending from the upper surface of the insulating layer to an upper electrode line and exposing an upper electrode surface portion of the upper electrode line; and a lower portion extending from the upper electrode line to an electrode surface portion of the lower electrode line.

[0030] Providing synthesis wells with lower and upper aperture portions allows for increased depth of the synthesis wells without increasing the vertical spacing between the lower and upper electrode lines. Deeper synthesis wells can help confine reaction conditions to the selected well. For example, when using a synthesis array, protons can be generated in the lower portion of the selected well. Exposing the upper aperture portion to the upper electrode surface of the upper electrode line allows for a larger area of ​​the upper electrode surface relative to the lower electrode surface. This allows reactions occurring at the lower electrode surface to be balanced at the upper electrode surface. Assuming, for example, the lower and upper electrode surface portions are configured as the working and counter electrodes, respectively, protons generated by oxidation at the working electrode can be consumed in redox reactions at the counter electrode. This, in turn, reduces proton outward diffusion, which can cause crosstalk between synthesis wells.

[0031] The cross-sectional area of ​​the upper portion of each hole can be greater than the cross-sectional area of ​​the lower portion of the hole. More specifically, the exposed portion of the upper electrode surface of the upper electrode wire can be greater than the exposed portion of the lower electrode surface.

[0032] Consistent with the above discussion, the upper electrode surface portion allows protons generated at the lower electrode surface portion of the lower electrode line to be largely consumed by the upper electrode surface portion of the upper electrode line. Therefore, the risk of protons escaping from the synthesis aperture is reduced.

[0033] The exposed surface area of ​​the upper electrode wire can be at least twice the area of ​​the exposed surface area of ​​the lower electrode wire. Alternatively, the exposed surface area of ​​the upper electrode wire can be approximately three times the area of ​​the exposed surface area of ​​the lower electrode wire.

[0034] This ensures that the surface area of ​​the upper electrode portion is sufficiently large relative to the surface area of ​​the lower electrode portion.

[0035] Each lower electrode line may include a selector stack at each synthesized via, the selector stack comprising a lower metal layer, an upper metal layer, and an intermediate layer of semiconductor or insulating material, wherein the selector stack may form a selector diode, and wherein the electrode surface portion of the lower electrode line may be the upper surface portion of the upper metal layer.

[0036] In other words, the selector diode can be connected in series with the synthesis via. The selector diode can have a non-linear current response to a potential applied to its terminals. This can be advantageous because it ensures that the non-linearity of the resistance on the selected synthesis via is minimized, regardless of the specific chemical reaction being driven. The selector diode can have a symmetrical current-voltage relationship (IV). This allows the selector diode to drive reactions requiring either a negative or positive potential. The selector diode can be any two-terminal diode. The selector diode can be a back-to-back Schottky diode. The diode can be a metal-semiconductor-metal (MSM) tunneling diode. The diode can be a metal-insulator-metal (MIM) tunneling diode.

[0037] Each electrode surface portion of the lower electrode line can be configured as a working electrode, and each electrode surface portion of the upper electrode line can be configured as a counter electrode.

[0038] Therefore, in response to a positive (negative) voltage, the working electrode can act as a proton generating (consuming) electrode, and the counter electrode can act as a proton consuming (generating) electrode.

[0039] The vertical spacing between multiple lower electrode lines and multiple upper electrode lines can be smaller than the spacing between the synthesis vias. In other words, the vertical distance between the upper and lower electrode lines in a synthesis via can be smaller than the horizontal distance between two adjacent synthesis vias. This allows the preferred path for current flow to be formed by passing through the lower electrode line of the selected synthesis via rather than through adjacent synthesis vias.

[0040] The vertical spacing between the multiple lower electrode lines and the multiple upper electrode lines can be 40 to 300 nm, and the spacing of the synthesized holes can be at least twice the vertical spacing.

[0041] According to a second aspect of the invention, a molecular synthesis apparatus is provided. The molecular synthesis apparatus includes a molecular synthesis array according to the first aspect, and further includes an array controller configured to perform synthesis in selected synthesis holes by applying a voltage to the selected synthesis holes via lower and upper electrode lines intersecting at selected synthesis holes among a plurality of synthesis holes in the molecular synthesis array. In other words, the array controller can control the voltages of the upper and lower electrode lines to selectively control molecular synthesis in different synthesis holes.

[0042] The array controller can be further configured to perform synthesis in parallel in the selected synthesis holes via lower and upper electrode lines intersecting at each corresponding synthesis hole in a set of selected synthesis holes, by applying corresponding voltage pulse trains to the respective synthesis holes. The array controller can be configured to apply the voltage pulse trains simultaneously to the molecular synthesis array in a time-division multiplexed manner. That is, the voltage pulse trains can be applied to the synthesis array in parallel or simultaneously, but with a relative time offset, such that any two pulses in any two different voltage pulse trains do not overlap.

[0043] Due to the use of a crossbar array structure, selective addressing of a single synthesis well allows for the simultaneous activation of both an upper and lower electrode line. By employing the time-division multiplexing scheme described above, more time-efficient molecular synthesis processes can be performed on the molecular synthesis apparatus. More specifically, since the voltage pulse duration can be much shorter than the reaction time (e.g., 1 ms vs. 10 s), multiplexing can be performed using all upper and lower electrode lines associated with a set of selected synthesis wells, which works as efficiently as if all selected synthesis wells were activated simultaneously. To facilitate the multiplexing method, sufficient charge needs to be stored for a very short period to allow the reaction to continue occurring while multiplexing is performed through other electrode lines; as discussed above, this can be provided by the inherent capacitance of the synthesis well itself.

[0044] The molecular synthesis apparatus may further include a cover disposed on the molecular synthesis array and defining a synthesis compartment on the upper surface of an insulating layer for containing a solution comprising synthesis reagents, wherein the synthesis compartment may communicate with a plurality of orifices. Accordingly, the synthesis compartment and synthesis orifices of the molecular synthesis apparatus may contain a solution comprising synthesis reagents during use.

[0045] The molecular synthesis apparatus may further include: a set of reagent compartments, each configured to contain a reagent solution; an arrangement of fluid channels connecting the set of reagent compartments and a synthesis compartment and configured to transfer the reagent solution from each reagent compartment to the synthesis compartment; and a fluid controller configured to control the transfer of the reagent solution from the reagent compartment to the synthesis compartment.

[0046] According to a third aspect of the invention, a data storage system is provided. The data storage system includes a molecular synthesis apparatus according to a second aspect and a memory controller configured to receive an input data stream to be stored at selected locations in a synthesis array, and to enable an array controller to perform synthesis in selected synthesis wells based on the input data stream.

[0047] According to a fourth aspect of the invention, a method is provided for performing synthesis in selected synthesis wells of a molecular synthesis array of a molecular synthesis apparatus according to the second aspect. The method includes applying a voltage to the selected synthesis well via lower and upper electrode lines intersecting at the selected synthesis well.

[0048] The effects and features of the second, third, and fourth aspects of the invention are largely similar to those described above in conjunction with the first aspect of the inventive concept. The embodiments mentioned with respect to the first aspect of the invention are largely compatible with other aspects of the invention. To avoid excessive repetition, refer to the foregoing. Attached Figure Description

[0049] The above and other aspects of the inventive concept will now be described in more detail with reference to the accompanying drawings, which illustrate variations of the inventive concept. The drawings should not be construed as limiting the invention to specific variations; rather, they are used to explain and understand the inventive concept.

[0050] Figure 1 A molecular synthesis array according to an embodiment is illustrated schematically.

[0051] Figure 2A This is a three-dimensional cross-sectional view of the synthesis pores of a molecular synthesis array according to one embodiment.

[0052] Figure 2B This is a three-dimensional cross-sectional view of the synthesis pores of a molecular synthesis array according to another embodiment.

[0053] Figure 3A It includes Figure 2A A schematic circuit layout of a molecular synthesis array of the type of synthetic pores depicted.

[0054] Figure 3B It includes Figure 2B A schematic circuit layout of a molecular synthesis array of the type of synthetic pores depicted.

[0055] Figure 4 This is a schematic diagram of a molecular synthesis apparatus according to an embodiment.

[0056] Figure 5 This is a schematic diagram of a data storage system according to an embodiment.

[0057] Figure 6 This is a diagram illustrating the writing scheme of a molecular synthesis apparatus. Detailed Implementation

[0058] The inventive concept will now be described more fully below with reference to the accompanying drawings, in which embodiments are illustrated. However, the inventive concept can be practiced in many different forms and should not be construed as being limited to the variations set forth herein; rather, these variations are provided to achieve thoroughness and completeness and to fully communicate the scope of the inventive concept to those skilled in the art.

[0059] Now refer to Figures 1 to 6 Examples of molecular synthesis arrays, molecular synthesis apparatuses including molecular synthesis arrays, data storage systems including molecular synthesis apparatuses, and methods for performing synthesis in molecular synthesis apparatuses 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 apparatus. For example, some structures and layers may be exaggerated herein for illustrative purposes.

[0060] This invention can be applied to 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, and spatial transcriptomics. Furthermore, this invention 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. Understanding the data encoding scheme employed during writing—that is, the mapping between data symbols and the constructed structures of the synthetic molecules—allows the written data symbols to be read from the structure of the synthetic molecules accordingly, such as the sequence of monomers (for polymers) or the sequence of base pairs (for DNA or RNA). In other words, molecular synthetic arrays can be used to control the generation of oligonucleotide chains, which can be used to encode bit-like data.

[0062] According to the present invention, a molecular synthesis array is provided, comprising an array of synthesis wells defined at the intersection of lower and upper electrode lines, each well defining a corresponding synthesis location. Reagents for synthesis can be supplied to the synthesis wells via valves and channels (e.g., microfluidic channels). Subsequently, a synthetic chemical reaction can be achieved via a corresponding pair of lower and upper electrode lines intersecting at the selected synthesis wells by biasing the electrode surfaces at those wells. Hereinafter, reference will primarily be made to solid-phase DNA synthesis controlled by ion generation. However, it is envisioned that the molecular synthesis array can also be compatible with other synthetic reactions, wherein the reaction rate can be controlled by electrochemically induced redox reactions.

[0063] In situ synthesis of DNA microarrays is based on conventional solid-phase DNA synthesis. In short, successive synthetic cycles are performed to add phosphoramidite nucleotides to growing oligonucleotide chains bound to a surface. Each synthetic cycle can consist of four steps: phosphoramidite nucleotide coupling; end capping; phosphate backbone oxidation; and deprotection of the coupled nucleotides to allow the addition of the next phosphoramidite nucleotide. The locally controlled deprotection step (detriphenylmethylation) enables the addition of nucleotides only at the desired positions and thus allows for the parallel synthesis of multiple DNA chains.

[0064] On an electrode array (such as the molecular synthesis array of the present invention), the detriphenylmethylation step can be electrochemically induced. In short, the synthesis site (i.e., the synthesis pore) can be equipped with electrodes known to release hydrogen ions (e.g., H+) upon oxidation. + The solution washes away the triphenylmethylation of the proton redox pair (e.g., hydroquinone / benzoquinone, hydrogen / fluorine, hydrogen / chlorine, or any other redox pair in which the reaction is not diffusion-restricted (i.e., redox reaction dominated by Butler-Volmer kinetics)). If the addition of the next nucleotide is required, an oxidation potential can be applied relative to the working and counter electrodes at the synthesis site. The oxidation reaction occurring at the surface of the selected electrodes causes proton release at the electrode at the synthesis site, resulting in a local pH decrease that induces the removal of the DMT (dimethoxytriphenylmethyl) protecting group of the phosphoramidite bound to the oligonucleotide chain on the surface. In a subsequent step, the next nucleotide can be added to the chain.

[0065] As described above, molecular synthesis arrays utilize intersecting lower and upper electrode lines to selectively address synthesis holes in a manner conceptually similar to conventional crossbar addressing schemes. However, selective addressing is not as straightforward as in conventional memory chips. The main difference lies in the fact that, in the use of molecular synthesis arrays, all electrode lines are in contact with and electrically interconnected through reagent solutions. This makes selective addressing of the electrodes more difficult. However, as achieved by the inventors, an exponential correlation between voltage and current, similar to that of a Schottky diode, can be obtained between the (metallic) electrode surface of the lower electrode line in the synthesis hole and the synthesis reagent (e.g., a solution containing an active redox substance) (due to the Butler-Volmer kinetics of redox reactions). This mechanism can be used as a selector device between individual synthesis sites to avoid activating adjacent synthesis holes. Accordingly, proton generation in the selected synthesis hole can be exponentially correlated with the applied potential. Assuming a linear decrease in the potential between two adjacent synthesis holes (due to their separation), an exponential decrease in the amount of protons in adjacent (unselected) synthesis holes can be achieved. Furthermore, the reaction rate v of the synthesis reaction can depend linearly 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 the nucleoside with the DMT protecting group of phosphoramidite). The reactivity of the unselected synthesis well can be several orders of magnitude of the reactivity of the selected synthesis site, and therefore would require an exponentially increasing amount of time to produce the same result.

[0066] Figure 1 A molecular synthesis array 100 is illustrated schematically as an example. Specifically, Figure 1 A general crossbar array structure of the molecular synthesis array 100 is shown. An example of the layer structure of the molecular synthesis array 100 will be combined with... Figure 2A and Figure 2B Further discussion.

[0067] The molecular synthesis array 100 includes a plurality of lower electrode lines 104. In this example, the molecular synthesis array 100 includes eight lower electrode lines. However, it should be noted that the molecular synthesis array 100 may include any number of lower electrode lines. The plurality of lower electrode lines 104 extend parallel to each other along the column direction of the molecular synthesis array 100.

[0068] The molecular synthesis array 100 further includes a plurality of upper electrode lines 102. In this example, the molecular synthesis array 100 includes eight upper electrode lines. However, it should be noted that the molecular synthesis array 100 may include any number of upper electrode lines. In the example shown, the molecular synthesis array 100 includes the same number of upper and lower electrode lines. However, the molecular synthesis array 100 may include different numbers of upper and lower electrode lines. The plurality of upper electrode lines 102 extend parallel to each other along the row direction of the molecular synthesis array.

[0069] 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 and column directions can intersect each other at angles other than right angles (e.g., at a slightly inclined angle). Furthermore, the upper electrode line 102 and the lower electrode line 104 are physically and electrically vertically separated from each other. Therefore, the upper electrode line extends across the lower electrode line. It should be noted that even if the upper electrode line is described as extending in the row direction and the lower electrode line is described as extending in the column direction, the opposite can also be true.

[0070] The molecular synthesis array 100 further includes a plurality of synthesis wells 106. Each synthesis well can be used as a synthesis site for molecular synthesis performed on the molecular synthesis array 100. When the molecular synthesis array 100 is used in a data storage system, each synthesis well (or synthesis site) can be used as a bit unit. The plurality of synthesis wells 106 are formed at the intersection between the lower electrode lines and the upper electrode lines. In the molecular synthesis array 100 shown herein, there are eight upper electrode lines and eight lower electrode lines, thus allowing 64 individual synthesis wells to be formed. In each synthesis well, the electrode surface portions of the upper electrode lines and the lower electrode lines are exposed to allow for synthetic reactions. The structure of the synthesis wells will be described below. Figure 2A and Figure 2B Further description.

[0071] If combined Figure 4 Further described, the upper and lower electrode lines can be connected to an array controller configured to apply voltage to different electrode lines. The synthesis location (i.e., the synthesis aperture) can be selected by applying voltage to specific upper and lower electrode lines that intersect at the synthesis location.

[0072] The composite holes in the multiple composite holes 106 can be arranged at regular intervals along the row and column directions, such as Figure 1 As shown. The distance between two adjacent synthesis holes along the column or row direction can be called the pitch of the molecular synthesis array. Although Figure 1 The pitch along the column direction and the pitch along the row direction can be the same, but it is conceivable that the array can have different pitches along the column direction and the row direction.

[0073] Figure 2A This is a three-dimensional view of a portion of the molecular synthesis array 100. More specifically, Figure 2A A cross-section of synthesis aperture 200 and an adjacent synthesis aperture 224 are shown. Synthesis apertures 200 and 224 generally represent any pair of adjacent synthesis apertures arranged along the same lower electrode line among the plurality of synthesis apertures 106 of array 100. The structure of synthesis aperture 200 shown in cross-section will be described below. However, it should be noted that the same structure also applies to the other synthesis apertures of the molecular synthesis array 100.

[0074] As mentioned above Figure 1 As described, the molecular synthesis array 100 includes a plurality of lower electrode lines 104 and a plurality of upper electrode lines 102. The upper and lower electrode lines can be formed of any material suitable as an electrode material. Examples include, but are not limited to, platinum, gold, and ruthenium.

[0075] exist Figure 2A In the portion of the molecular synthesis array 100 shown, reference numerals 210 and 204 indicate a corresponding pair of lower and upper electrode lines that intersect at synthesis apertures 200. The lower electrode line 210 extends in the column direction (i.e., upwards and into the image plane). The upper electrode line 204 extends in the row direction (i.e., from one side to the other as viewed from the image plane). An upper electrode line 218 is also shown intersecting the lower electrode line 210 at an adjacent synthesis aperture 224, with this upper electrode line extending parallel to the upper electrode line 204.

[0076] like Figure 2AAs seen, the molecular synthesis array 100 further includes a substrate 208. The molecular synthesis array 100 further includes an insulating layer 202 disposed on the substrate 208. The insulating layer 202 may include one or more insulating materials. For example, the insulating layer 202 may include one or more layers of silicon oxide and / or silicon nitride. Upper electrode lines 204 and lower electrode lines 210 are embedded in the insulating layer 202. Specifically, the upper electrode lines 204 and lower electrode lines 210 may be completely encapsulated by the insulating layer 202, but a portion is exposed in the synthesis aperture 200. The upper electrode lines 204 and lower electrode lines 210 are vertically separated from each other. A portion 206b of the insulating layer 202 is thus disposed between the upper electrode lines 204 and lower electrode lines 210 to separate them from each other. The insulating layer 202 further includes an upper portion 206a disposed on and covering the upper electrode line 204. The upper portion 206a of the insulating layer 202 has a thickness represented by h2. This thickness can be from 40 to 300 nm. The lower electrode line 210 can be disposed directly on the (non-conductive) surface portion of the substrate 208. However, the lower electrode line 210 can also be disposed within the insulating layer 202 so that it is omnidirectionally surrounded by the insulating layer.

[0077] A synthesis aperture 200 is formed at the intersection between the upper electrode line 204 and the lower electrode line 210. The synthesis aperture 200 extends from the upper surface 226 of the insulating layer 202 to the lower electrode line 210. Therefore, the synthesis aperture 200 extends through the insulating layer 202 and through the upper electrode line 204. The synthesis aperture 200 thus exposes the electrode surface portion 222 of the upper electrode line 204 and the electrode surface portion 216 of the lower electrode line 210. The electrode surface portion 216 of the lower electrode line 210 can form the bottom surface of the synthesis aperture 200. The exposed electrode surface portion 222 of the upper electrode line 204 and the exposed electrode surface portion 216 of the lower electrode line 210 can therefore be used as the electrode surface of the synthesis aperture 200. In particular, the electrode surface portion 216 of the lower electrode line 210 can be configured as the working electrode of the synthesis aperture 200. The electrode surface portion 222 of the upper electrode line 204 can be configured as the counter electrode of the synthesis aperture 200.

[0078] The synthetic hole 200 is shown herein as a circular hole. However, as those skilled in the art will recognize, the synthetic hole 200 may also have other shapes, such as polygonal or elliptical.

[0079] The synthetic via 200 may include an upper portion 212 and a lower portion 214, as shown. The upper portion 212 and the lower portion 214 of the synthetic via 200 may be centered relative to a common central axis as seen along a vertical direction (e.g., toward the substrate). The upper portion 212 extends from the upper surface 226 of the insulating layer 202 to the upper electrode line 204, exposing the upper electrode surface portion 221 of the upper electrode line 204. The lower portion 214 of the synthetic via 200 extends from the upper electrode line 204 and passes through it to reach the electrode surface portion 216 of the lower electrode line 210. (As shown in...) Figure 1 As seen in the image, the upper electrode surface portion 221 circumferentially surrounds the topmost portion (i.e., the hole in the upper electrode line 204) formed by the lower portion 214 of the synthetic hole 200 passing through the upper electrode line 204.

[0080] The lower portion 214 of the synthetic hole 200 has a first diameter as indicated by the mark d1. The upper portion 212 of the synthetic hole 200 has a second diameter as indicated by the mark d2. Figure 2A As can be seen, d2 is greater than d1, causing the cross-sectional area of ​​the upper portion 212 (as seen along the vertical direction) to exceed the cross-sectional area of ​​the lower portion 214. In particular, the area A2 of the exposed upper electrode surface portion 221 of the upper electrode line 204 can be greater than the area A1 of the exposed electrode surface portion 216 of the lower electrode line 210.

[0081] The determination of the size of the synthesis array 100 is a trade-off between (1) ensuring that the area A2 (relative to the area A1) is large enough to facilitate the synthesis reaction and reduce the risk of crosstalk; and (2) keeping the area A2 small enough to also allow for small pitch (and thus high density) of the synthesis array 100.

[0082] The diameters d1 and d2 of the upper portion 212 and the lower portion 214 of the synthetic hole 200, as well as the pitch p, can be determined as follows.

[0083] The area A1 of the exposed electrode surface portion 216 of the lower electrode line 210 can be expressed as:

[0084] A1=πr1 2 ,

[0085] Where r1 is the radius of the lower portion 214 of the synthesis hole 200. Therefore, the area A2 of the exposed upper electrode surface portion 221 of the upper electrode line 204 (ignoring the side surface portion 220 of the upper electrode line 204) can be expressed as:

[0086] A2=πr2 2 -πr1 2 ,

[0087] Where r2 is the radius of the upper portion 212 of the synthetic hole 200. The relationship between A2 and A1 can be expressed by the formula:

[0088] A2 = αA1,

[0089] Where α is a scaling factor. Preferably, A2 is equal to or greater than A1 (i.e., α ≥ 1). More preferably, A2 is greater than A1 (i.e., α > 1). Even more preferably, A2 is at least twice A1 (α ≥ 2).

[0090] Considering the expressions for A1 and A2 above, the relationship between A2 and A1 can be rewritten as follows:

[0091] πr2 2 -πr1 2 =απr1 2

[0092] r2 2 =(1+α)r1 2

[0093]

[0094] As an example, assuming the diameter of the lower portion 214 of the synthetic aperture 200 is chosen to be 20 nm (i.e., d1 = 20 nm), and the area A1 of the exposed electrode surface portion 216 of the lower electrode line 210 should be half the area A2 of the exposed upper electrode surface portion 221 of the upper electrode line 204 (i.e., α = 2), then the diameter of the upper portion 212 of the synthetic aperture 200 will be 34.64 nm (i.e., d2 = 34.64 nm). As a non-limiting example, d1 can be 20 nm or greater, and d2 can be 35 nm or greater. The pitch p can be 80 nm or greater.

[0095] Possible minimum pitch p min It can be represented as

[0096] p min =d2+CD,

[0097] CD is the critical dimension of the electrode line spacing (e.g., along the row or column direction) for a technical node in the manufacturing process used to pattern the electrode lines. The critical dimension can typically be the same as the diameter of the lower portion 214 of the synthetic aperture 200. In the example above, a critical dimension CD of, for example, 20 nm would therefore result in a minimum pitch p of 54.64 nm. min .

[0098] As an alternative to upper hole portions 212 and lower hole portions 214 of different diameters, considering that the width of the composite hole 200 can be the same along the depth dimension of the composite hole 200, in this case, the electrode surface portion 222 of the upper electrode line 204 can be a side surface portion 220 of the upper electrode line 204, which surrounds the opening through the upper electrode line.

[0099] In any case, the vertical spacing between the lower electrode line 210 and the upper electrode line 204 can be smaller than the spacing between the synthesis aperture 200 and the adjacent synthesis aperture 224 (i.e., the pitch of the molecular synthesis array 100), because this improves the selectivity of the addressing scheme.

[0100] Given the distance h1 between the lower electrode surface portion 216 and the upper electrode surface portion 221 in the synthetic aperture 200 (see... Figure 2A The depth h2 of the upper portion 212 of the synthetic hole 200 (i.e., the distance between the upper surface 226 of the insulating layer 202 and the upper electrode surface portion 221, see...) Figure 2A The distance D between the upper electrode surface portion 221 of the selected synthesis hole 200 and the lower electrode surface portion of the adjacent unselected synthesis hole 224 along the same lower electrode line 210 (i.e., the same column) is given by the following formula (ignoring the thickness of the upper electrode line 204):

[0101] D = h1 + 2h2 + p

[0102] Accordingly, the amount by which D exceeds h1 depends on the values ​​of h2 and p. Therefore, the preferred path for current flow in the reagent solution will pass through the selected synthesis well 200, but not through adjacent synthesis wells 224 (e.g., assuming the conductivity of the reagent solution within the lower well portion 214 of synthesis well 200 is not several orders of magnitude greater than the conductivity of the reagent solution in the upper well portion 212 and outside synthesis well 200). As a non-limiting example, where h1 and h2 are 300 nm and p is 3000 nm, then D = 3900 = 13h1. More generally, h1 can be from 40 to 300 nm, h2 can be from 40 to 300 nm, and p can be at least twice h1.

[0103] As can be understood, the actual resistance value will depend on the composition of the reagent solution used, or more specifically, on the ionic conductivity of the reagent solution. The ionic conductivity of the reagent solution depends on the ion concentration (e.g., salt content) of the reagent solution. The higher the salt content, the higher the conductivity. In practice, the ion concentration of the reagent solution should be selected such that the resistance between the lower electrode surface portion 216 and the upper electrode surface portion 221 of the selected synthesis well is approximately equal to the electron tunneling resistance (i.e., charge transfer resistance) between the electrode surface and the reagent solution.

[0104] Given a certain value for distance h2, distance h1 can be chosen as any value, with the maximum value given by the following formula:

[0105]

[0106] Table 1 shows several examples of d1 and different values ​​of d2, p, and h1 when α = 2 and h2 = 100.

[0107] Table 1

[0108]

[0109] Table 2 shows several examples of d1 and different values ​​of d2, p, and h1 when α = 1 and h2 = 100.

[0110] Table 2

[0111]

[0112]

[0113] Figure 2B This is a perspective view of a portion of a molecular synthesis array 100' including synthesis pores according to another embodiment. More specifically, Figure 2B A cross-section of such a synthesis aperture 200' is shown. Reference numeral 224' denotes adjacent synthesis apertures along the same column. Synthesis apertures 200' and 224' generally represent any pair of adjacent synthesis apertures of array 100' arranged along the same lower electrode line. The structure of the synthesis aperture 200' shown in cross-section will be described below. However, it should be noted that the same structure applies to the other synthesis apertures of the molecular synthesis array 100'.

[0114] because Figure 2B Molecular synthesis array 100' and Figure 2A The molecular synthesis arrays 100 share many features, so refer to the above to avoid excessive repetition. Instead, the following discussion focuses on... Figure 2A The structural differences. Figure 2B In the figures, the reference numerals are followed by a single quotation mark ('), unless otherwise specified, which corresponds to... Figure 2A Features similar to the numbering in the middle.

[0115] The lower electrode line 210' of the synthesis aperture 200' includes a selector stack 211' located below the synthesis aperture 200'. The selector stack 211' includes a lower metal layer 232', an upper metal layer 228', and an intermediate layer 230'. As shown herein, the intermediate layer 230' is disposed between the lower metal layer 232' and the upper metal layer 228'. The intermediate layer 230' can be formed of a semiconductor material or an insulating material, or a stack of different semiconductor materials or insulating materials. Examples of semiconductor materials include, but are not limited to, aSi, Si, IGZO, and two-dimensional materials such as MoS2, MoSe2, and WSe2. The selector stack 211' can form a selector diode for the synthesis aperture 200'. The selector diode 211' can therefore be used as a selector for the synthesis aperture 200', thereby improving the selectivity of the molecular synthesis array 100. In the case of selector stacks, the upper surface portion of the upper metal layer 228' can form the electrode surface portion 216' of the lower electrode line 210' at the composite hole 200', while the lower metal layer 232' can form the lower electrode line extending along the column direction.

[0116] The selector stack along each lower electrode line 210' can be formed as a corresponding layer stack on a continuous metal line. In other words, the lower electrode line 210' can be formed by a lower metal layer 232' that is a continuous line along the entire column. At each intersection between the lower electrode line 210' and the upper electrode line 204', a layer stack of intermediate layer 230' and upper metal layer 228' can be formed on top of the (continuous) electrode line 210'. In other words, the selector stack can be formed as an island along a continuous metal line. Alternatively, all layers of the selector stack can be a continuous line. In other words, the selector stack can be formed by a continuous line of lower metal layer 232', intermediate layer 230', and upper metal layer 228' extending along the entire column.

[0117] Figure 3A A schematic diagram of the circuit layout of the molecular synthesis array 100 is shown as an example. Figure 3A The circuit layout corresponds to the above combined Figure 2A An example of a molecular synthesis array 100 with a synthesis pore 200 is described.

[0118] For illustrative purposes, the molecular synthesis array 100 is shown herein as having four lower electrode lines C1 to C4 and four upper electrode lines R1 to R4. For each pair of lower and upper electrode lines, a synthesis aperture 200 is provided, resulting in 16 synthesis apertures. Each synthesis aperture has an electrode surface portion 216 of the lower electrode line and an electrode surface portion 222 of the upper electrode line as described above. To clearly illustrate the electrical connections of the molecular synthesis array 100, the synthesis aperture is shown on one side of the intersection between the upper and lower electrode lines. However, it should be noted that the synthesis aperture, as described above, is formed at the intersection between the upper and lower electrode lines. As described above, the electrode surface portion 216 of the lower electrode line can be used as a working electrode, and the electrode surface portion 222 of the upper electrode line can be used as a counter electrode.

[0119] As an example, a synthesis aperture at the intersection of C2-R4 can be activated by applying a voltage to the second lower electrode line C2 and the fourth upper electrode line R4. The methods for controlling each synthesis aperture will be described below. Figure 6 describe.

[0120] Figure 3B A schematic diagram of the circuit layout of the molecular synthesis array 100' is shown as an example. Figure 3B The circuit layout corresponds to the above combined Figure 2B An example of a molecular synthesis array 100' with a synthesis pore 200' is described.

[0121] like Figure 3A As shown, the molecular synthesis array 100' is presented herein as having four lower electrode lines C1 to C4, four upper electrode lines R1 to R4, and 16 synthesis wells.

[0122] and Figure 3A The molecular synthesis array 100 is the opposite. Figure 3B The molecular synthesis array 100' further includes a selector stack / diode 211'. The selector diode 211' is connected in series between the lower electrode line (e.g., C1-C4) and the electrode surface portion 216' of the lower electrode line.

[0123] In this molecular synthesis array 100, in addition to the selector diode 211', the nonlinearity of the electrochemical reaction itself (e.g., due to the Butler-Volmer kinetics of the reaction) also acts as a selector for each synthesis aperture. Because the selector diode 211' introduces nonlinearity, the selectivity between synthesis apertures depends to a lesser extent on the nonlinearity of the electrochemical reduction itself.

[0124] Figure 4 This is a schematic diagram of a molecular synthesis apparatus 400. The molecular synthesis apparatus 400 includes a binding... Figures 1 to 3BThe molecular synthesis array 100 or 100' in any of the described embodiments. The molecular synthesis apparatus 400 further includes an array controller 402. The array controller 402 is configured to perform synthesis in selected synthesis holes among a plurality of synthesis holes of the molecular synthesis array 100. The array controller 402 can perform synthesis by applying a voltage to the selected synthesis hole via lower and upper electrode lines crossing at the selected synthesis hole. For the purpose of providing voltage and current to the electrode lines, the array controller 402 may include a driver circuit system comprising column line drivers and row line drivers. The function and implementation of such a driver circuit system are known to those skilled in the art and will therefore not be described further herein.

[0125] The array controller 402 can be further configured to perform synthesis in parallel across a set of selected synthesis wells. Parallel synthesis can be performed via lower and upper electrode lines crossing at corresponding synthesis wells within the set of selected synthesis wells, by applying a corresponding voltage pulse train to each corresponding synthesis well, wherein the voltage pulse trains are simultaneously applied to the molecular synthesis array 100 in a time-division multiplexed manner. The following is in conjunction with... Figure 6 Further examples of how synthesis can be performed using time-division multiplexing are provided.

[0126] The molecular synthesis apparatus 400 may further include a cover disposed on the molecular synthesis array 100 to define a synthesis compartment or fluid pool 410 on the upper surface of an insulating layer for receiving and containing a solution (i.e., a reagent solution) containing synthesis reagents. The synthesis compartment 410 may communicate with a plurality of synthesis wells. Accordingly, the solution received in the synthesis compartment 410 may flow into and fill the synthesis wells.

[0127] The molecular synthesis apparatus 400 may further include a set of reagent compartments 406A-C. Each reagent compartment in this set of reagent compartments 406A-C may be configured to contain a reagent solution. Different reagent compartments in this set of reagent compartments 406A-C may contain different reagent solutions, such as reagent compartments containing solutions with different phosphoramidine nucleotides, and reagent compartments containing solutions including redox pairs of detrimethylated solutions (e.g., facilitating proton release in selected synthesis wells and thus enabling synthetic reactions to take place therein).

[0128] The molecular synthesis apparatus 400 may further include an arrangement of fluid channels 408A-C connecting the group of reagent compartments 406A-C to the synthesis compartment 410, and configured to transfer reagent solutions from each reagent compartment to the synthesis compartment 410. The fluid channels may be, for example, microfluidic channels. Additional fluid channels may be present for managing the flow of reagent solutions within the molecular synthesis apparatus 400.

[0129] The molecular synthesis apparatus 400 may further include a fluid controller 404. The fluid controller 404 may be configured to control the transfer of a reagent solution from reagent compartments 406A-C to synthesis compartment 410. The fluid controller 404 may be, for example, a microfluidic controller. The fluid controller 404 may control the flow of the reagent solution using techniques known in the art itself (e.g., by controlling valves arranged along fluid channels 408A-C).

[0130] Molecular synthesis apparatus 400 can be configured to synthesize oligonucleotides bound to the lower electrode surface portions of the synthesis wells of synthesis arrays 100, 100' using solid-phase DNA synthesis. The apparatus 400 can be configured to perform synthesis in selected synthesis wells (or multiplexed in a group of selected synthesis wells) by applying a voltage to the selected synthesis wells via lower and upper electrode lines crossing at the selected synthesis wells, thereby causing deprotection of the protected nucleosides of the oligonucleotide chains bound to the lower electrode surfaces of the selected synthesis wells. Nucleotides from a reagent solution can then be added to the oligonucleotide chains. As described above, the applied voltage can induce an oxidation reaction of the redox pair in the reagent solution, allowing protons to be released at the electrode surfaces and achieving deprotection (e.g., removal of protecting groups from the oligonucleotide chains). This process can be repeated to sequentially add nucleotides to the oligonucleotide chains. The type of nucleotide added can vary by changing the reagent solution containing the desired type of nucleotide (e.g., adenine, cytosine, thymine, or guanine (A, C, T, G)).

[0131] In addition to inducing deprotection via proton generation (which means applying a positive voltage to the lower electrode surface portion (working electrode) and upper electrode surface portion (counter electrode) of the selected synthesis wells to enable the addition of nucleotides to oligonucleotide chains), a negative voltage can be applied to enable the grafting process. Grafting refers to the process of functionalizing the working electrode for synthesis, i.e., attaching one or more anchoring molecules (such as diazo compounds) to the lower electrode surface portion, on which (corresponding) oligonucleotide chains can be synthesized. Like nucleotide addition, grafting can be selectively achieved by applying a negative voltage to the lower electrode surface portion and upper electrode surface portion of the selected synthesis wells. However, alternatively, grafting can be achieved non-selectively (i.e., in all synthesis wells of the synthesis array) as an initialization step prior to (selective) sequential oligonucleotides in the synthesis wells. As can be understood, the amplitudes of the positive voltage (for deprotection) and the negative voltage (for grafting) can be different.

[0132] Figure 5 This is a schematic diagram of a data storage system 500. The data storage system 500 includes, for example, the components described above. Figure 4 The molecular synthesis apparatus 400 is described. The data storage system 500 further includes a memory controller 502. The memory controller 502 is configured to receive an input data stream to be stored at a selected location in the molecular synthesis array of the molecular synthesis apparatus 400. The memory controller 502 may be configured to cause a fluid controller 404 to supply appropriate reagent solutions to the synthesis arrays 100, 100' in response to the input data stream. The memory controller 502 may be further configured to enable the array controller of the molecular synthesis apparatus 400 to perform synthesis in selected synthesis wells based on the input data stream. Therefore, the data storage system 500 allows data to be stored in the molecular synthesis apparatus 400 during molecular synthesis.

[0133] The memory controller 502 can 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 can be stored in a quaternary system. In other words, the memory controller 502 can convert the data symbols of the input data stream from binary format to a "polymer" field, where the input data stream is represented as a polymer sequence. The memory controller 502 can then synthesize polymer sequences in one or more selected synthesis wells.

[0134] Figure 6 This demonstrates the molecular synthesis apparatus (such as those described above). Figure 4 A diagram showing a scheme for achieving synthesis in one or more selected synthesis wells of the described molecular synthesis apparatus 400.

[0135] In the simplest case, where only a single synthesis aperture is addressed (i.e., data is written to it), a single activation pulse of sufficient length to complete the reaction can be applied to the corresponding upper and lower electrode lines. When the synthesis aperture is activated, the activation pulse (i.e., a voltage pulse) causes a positive or negative bias to be applied to the aperture depending on the reaction to be performed (e.g., deprotection or grafting). Therefore, the polarity of the activation pulse applied to the lower and upper electrode lines of the selected synthesis aperture can be positive or negative. The upper and / or lower electrode lines coupled to unselected synthesis apertures can remain suspended (e.g., disconnected from the drive circuitry from the array controller). Reference Figure 3A or Figure 3B By simultaneously applying activation pulses to the corresponding electrode lines R1 and C2 (such as...) Figure 6 (As seen in the diagram), a synthesis orifice can be enabled at the intersection between R1 and C2. The magnitude of the voltage applied to the selected synthesis unit should exceed the overpotential of the redox reaction. Figure 3AIn this context, the overpotential can depend on the exponential correlation between voltage and current arising from the Butler-Volmer kinetics of the redox reaction. Figure 3B In this context, the overpotential can depend on a combination of the exponential correlation between voltage and current resulting from the Butler-Volmer kinetics of the redox reaction and the threshold voltage of the selector diode 211'.

[0136] like Figure 6 Furthermore, it is pointed out that synthesis can be simultaneously achieved in other synthesis holes arranged along the same upper electrode line, for example, by simultaneously applying an activation pulse along C4, and simultaneously achieving synthesis in the synthesis hole at the intersection between R1 and C4. More specifically, by applying activation / voltage pulse trains to the synthesis array in a time-division multiplexed manner, the synthesis reaction can be achieved in parallel in a set of synthesis holes. Now, reference will be made to... Figure 6 And simultaneously at the intersections of R1-C2, R1-C4, R2-C1 and R2-C3 (e.g. Figure 3A and Figure 3B This method is described by an example of synthesis implemented in the document (see below). Figure 6 The first cycle of multiple pulse trains is illustrated. Each pulse train is applied to the corresponding upper or lower electrode line. As mentioned above, the pulse represents the activation of the individual upper and lower electrode lines, rather than the application of actual potentials (depending on the type of reaction). The corresponding "activation pulses" applied to rows R1-R4 and columns C1-C4 can therefore be referred to as row address gating pulses and column address gating pulses, respectively. The duration of the first cycle can correspond to the time during which the inherent capacitance of each synthesis well (even without 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 well is complete.

[0137] The first cycle is divided into four time periods. Each time period corresponds to the duration of each pulse, t. ON The pulse length is indicated.

[0138] During the first time period, an activation pulse is applied to the first upper electrode line R1. Additionally, activation pulses are applied to the second lower electrode line C2 and the fourth lower electrode line C4. Therefore, the synthesis holes R1-C2 and R1-C4 are activated for a period of time t. ON Subsequently, the first upper electrode line R1, the second lower electrode line C2, and the fourth lower electrode line C4 are deactivated for the remainder of the first cycle.

[0139] During the second time period, an activation pulse is applied to the second upper electrode line R2. Additionally, activation pulses are applied to the first lower electrode line C1 and the third lower electrode line C3. Therefore, the synthesis holes R2-C1 and R2-C3 are activated for a period of time t. ON They were subsequently discontinued.

[0140] In the third and fourth time periods, activation pulses are applied to the third and fourth upper electrode lines, respectively. However, since no lower electrode lines are activated, these pulse trains do not generate any activated synthetic vias. To achieve a more efficient addressing scheme, synthetic vias that do not activate can be skipped.

[0141] As described above, the pulse cycle shown in this paper can be repeated, so that the synthesis holes R1-C2 and R1-C4 are reactivated in subsequent time periods, and so on.

[0142] This example illustrates how multiple synthesis apertures can be activated simultaneously by applying an activation pulse train. This can be achieved by shortening the pulse length t. ON It can enable more synthesis holes at the same time.

[0143] Furthermore, variations of the disclosed variants can be understood and implemented by a person skilled in the art when practicing the claimed invention by studying the drawings, the disclosure, and the appended claims.

Claims

1. A molecular synthesis array (100, 100'), comprising: Substrate (208, 208'); An insulating layer (202, 202') is disposed on the substrate (208, 208'); A plurality of lower electrode lines (104) and a plurality of upper electrode lines (102) extend parallel to each other along the column direction of the molecular synthesis array (100, 100') and parallel to each other along the row direction of the molecular synthesis array (100, 100'). The upper electrode lines (102) are vertically separated from the lower electrode lines (104) and extend across the lower electrode lines (104). The lower electrode lines (104) and upper electrode lines (102) are embedded in the insulating layer (202, 202'). Multiple synthetic holes (106, 200, 200') are formed at the intersection between the lower electrode line (210, 210') and the upper electrode line (204, 204'), and extend from the upper surface (226) of the insulating layer (202, 202'), through the insulating layer (202, 202') and through the upper electrode line (204, 204') to the lower electrode line (210, 210'), and expose the electrode surface portions (222, 222') of the upper electrode line (204, 204') and the electrode surface portions (216, 216') of the lower electrode line (210, 210').

2. The molecular synthesis array (100, 100') according to claim 1, wherein, Each of the plurality of synthetic vias (106, 200, 200') includes: an upper portion (212, 212') extending from the upper surface (226, 226') of the insulating layer (202, 202') to the upper electrode line (204, 204') and exposing the upper electrode surface portion (221, 221') of the upper electrode line (204, 204'); and a lower portion (214, 214') extending from the upper electrode line (204, 204') to the electrode surface portion (216, 216') of the lower electrode line (210, 210').

3. The molecular synthesis array (100, 100') according to claim 2, wherein, The cross-sectional area of ​​the upper portion (212, 212') of each synthetic hole is greater than the cross-sectional area of ​​the lower portion (214, 214') of the synthetic hole.

4. The molecular synthesis array (100, 100') according to claim 2, wherein, The area of ​​the exposed upper electrode surface portion (221, 221') of the upper electrode line (204, 204') is at least twice the area of ​​the exposed electrode surface portion (216, 216') of the lower electrode line (210, 210').

5. The molecular synthesis array (100') according to claim 1, wherein, Each lower electrode line (210') includes a selector stack at each composite via (200'), the selector stack including a lower metal layer (232'), an upper metal layer (228'), and an intermediate layer (230') of semiconductor or insulating material, wherein the selector stack forms a selector diode (211'), and wherein the electrode surface portion (216') of the lower electrode line (210') is the upper surface portion of the upper metal layer (228').

6. The molecular synthesis array (100, 100') according to claim 1, wherein, Each electrode surface portion (216, 216') of the lower electrode line (104) is configured as a working electrode, and each electrode surface portion (222, 222') of the upper electrode line (102) is configured as a counter electrode.

7. The molecular synthesis array (100, 100') according to claim 1, wherein, The vertical spacing between the plurality of lower electrode lines (104) and the plurality of upper electrode lines (102) is smaller than the spacing between the synthetic holes (106, 200, 200').

8. The molecular synthesis array (100, 100') according to claim 1, wherein, The vertical spacing between the plurality of lower electrode lines (104) and the plurality of upper electrode lines (102) is 40 to 300 nm, and the spacing between the synthetic apertures (106, 200, 200') is at least twice the vertical spacing.

9. The molecular synthesis array (100, 100') according to claim 1, wherein, The plurality of lower electrode lines (104) and the plurality of upper electrode lines (102) are formed of ruthenium.

10. A molecular synthesis apparatus (400) comprising a molecular synthesis array (100, 100') according to claim 1, and further comprising an array controller (402) configured to perform synthesis in a selected synthesis hole by applying a voltage to the selected synthesis hole via a lower electrode line and an upper electrode line intersecting at a selected synthesis hole among a plurality of synthesis holes in the molecular synthesis array (100, 100').

11. The molecular synthesis apparatus (400) according to claim 10, wherein, The array controller (402) is further configured to perform synthesis in parallel in the set of selected synthesis holes by applying a corresponding voltage pulse train on the corresponding synthesis hole via the lower electrode line and the upper electrode line crossing at each corresponding synthesis hole in the set of selected synthesis holes, wherein the array controller (402) is configured to apply the voltage pulse train to the molecular synthesis array simultaneously in a time-division multiplexing manner.

12. The molecular synthesis apparatus (400) according to claim 10, further comprising a cover disposed on the molecular synthesis array and defining a synthesis compartment (410) on the upper surface of the insulating layer for containing a solution comprising the synthesis reagents, wherein, The synthesis compartment (410) is connected to the plurality of synthesis holes.

13. The molecular synthesis apparatus (400) according to claim 12, further comprising: A set of reagent compartments (406A-C), each reagent compartment being configured to contain a reagent solution; The arrangement of fluid channels (408A-C), which connect the reagent compartments (406A-C) to the synthesis compartment (410), and configured to transfer reagent solutions from each reagent compartment (406A-C) to the synthesis compartment (410); and A fluid controller (404) is configured to control the transfer of the reagent solution from the reagent compartment (406A-C) to the synthesis compartment (410).

14. A data storage system (500) comprising the molecular synthesis apparatus (400) according to claim 10 and a memory controller (502) configured to receive an input data stream to be stored at a selected location in the synthesis array and to enable the array controller to perform synthesis in a selected synthesis well based on the input data stream.

15. A method for performing synthesis in selected synthesis holes of a molecular synthesis array (100, 100') of a molecular synthesis apparatus (400) according to claim 10, the method comprising applying a voltage to the selected synthesis hole via a lower electrode line and an upper electrode line intersecting at the selected synthesis hole.

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