An adaptive printing data generation method and device for a DNA inkjet printing device

Abstract

The present application relates to a kind of DNA inkjet printing equipment adaptive printing data generation method and equipment, belong to synthetic biology field.The present application is analyzed by the position relationship between reaction site and ink dot, and by the way of subpixel shift, the spacing between the center of reaction site and row ink dot, column ink dot is grouped, and template is constructed.Through the way of constructing template, for later, same size reaction site, only the center position of reaction site is obtained, that is, the printing position of preset ink dot can be directly obtained by template, greatly reduce the amount of calculation, improve printing efficiency.The present application is preferably, when the ink dot spacing of DNA printing equipment in Y direction is greater than the spacing in X direction, the influence of X direction ink dot is ignored, template is constructed, further reduce the amount of calculation, improve efficiency.

Description

Technical Field

[0001] This invention relates to the field of synthetic biology, specifically to an adaptive printing data generation method and device for DNA inkjet printing. Background Technology

[0002] In the field of biology, automated DNA synthesis is an emerging DNA synthesis method in synthetic biology. Current DNA inkjet printing equipment applies the principles of inkjet printing to the DNA synthesis process. Just as an inkjet printer sprays ink onto paper to form a pattern, DNA inkjet printing equipment sprays different nucleotide monomer solutions through tiny nozzles onto the surface of a specific solid support, adding nucleotides sequentially according to a preset sequence to gradually synthesize the desired DNA fragments. The aforementioned solution is also called an ink dot.

[0003] Existing DNA inkjet printing equipment uses nozzles to spray ink droplets onto the reaction sites of a DNA chip, which has multiple circular reaction sites arrayed on it. DNA inkjet printing equipment utilizes inkjet printing technology to formulate ink containing the four bases (ATCG) required for gene synthesis, along with an activator. This ink is then precisely printed onto different reaction sites on the DNA chip, ensuring thorough mixing of the base ink and activator ink for efficient reaction.

[0004] Because the reaction sites are very small, it is generally required to precisely spray the solution to the center of the reaction site. Therefore, high-precision spraying is needed to improve synthesis accuracy. The accuracy and resolution of DNA inkjet printing equipment are related. For the printing coordinates of a DNA inkjet printer, its three-dimensional coordinate system is XYZ, where X and Y directions are the horizontal and vertical directions of the horizontal plane, and Z direction is the vertical direction. During spraying, the Z direction, i.e., its height direction, is relatively fixed. The DNA chip is fixed on a horizontal mount; therefore, its resolution is the resolution in the X and Y directions. If the X direction is defined as its stepping direction, its resolution is related to its stepping accuracy. The Y direction is the direction of the nozzle, and the nozzle array has orifices; its resolution is related to the spacing between the orifices. For a printing device, with fixed X and Y direction resolutions, the distance between adjacent ink dots in the X and Y directions is fixed. Since the distance between adjacent ink dots is fixed, after determining the origin position, the distribution of ink dots on the image is fixed. For example, a 600 DPI nozzle has a spacing of approximately 42.3 micrometers between its nozzles and a stepping accuracy of 5 micrometers. Therefore, the coverage area of ​​its ink dots is an array of ink dots with a row spacing of 42.3 micrometers and a column spacing of 5 micrometers.

[0005] Taking the circular reaction sites of a commonly used DNA chip in the form of a glass slide as an example, their diameter is typically 100-300 micrometers. Assuming the lower left corner of a standard glass slide is the dot, the length direction of the slide is the X-axis, and the width direction is the Y-axis, then in the pixel coordinate system, for a DNA inkjet printer with fixed precision in the X and Y directions, the positions of the printable ink dots are fixed. That is, there are multiple ink dot positions within the reaction site, such as 60 ink dots. However, a single reaction site usually requires multiple ink dot printing positions, such as 9 or 17. Therefore, the problem arises of how to select the optimal 9 or 17 ink dots from the aforementioned 60 ink dots.

[0006] The current method involves selection either randomly or through linear compensation calculation. The random method tends to select ink dots at the edge of the reaction site, while the calculation method suffers from extremely low printing efficiency due to the sheer number of reaction sites, especially for high-throughput DNA chips, such as the inventor's patent application CN121003955B, which states that the aforementioned high-throughput gene DNA chip has tens of thousands of reaction sites, resulting in an enormous computational load. This makes it difficult to adjust in real time and achieve commercialization.

[0007] Therefore, how to automatically calculate the position information of the ink droplets used in each reaction site according to the number of ink droplets to be printed, so that the ink droplets carrying DNA printing material can fall accurately into the reaction site area, is a technical problem that urgently needs to be solved.

[0008] Therefore, there is a need for an adaptive printing data generation method and system for DNA inkjet printing equipment, which can obtain the position information of the ink droplets used in each site according to the number of ink droplets to be printed, so that the ink droplets carrying DNA printing material can fall precisely into the reaction site area. The position information of the ink droplets can be directly sent to the printhead controller for precise inkjet printing. Summary of the Invention

[0009] The present invention is proposed to alleviate or solve at least one aspect or point of the above-mentioned problems.

[0010] The present invention discloses an adaptive printing data generation method for a DNA inkjet printing device, wherein the DNA inkjet printing device uses a nozzle to spray ink droplets onto the reaction sites of a DNA chip, and the DNA chip has multiple reaction sites arrayed on it. The method includes the following steps: Obtain the physical dimensions of the DNA chip, as well as the coordinates of the center of the reaction site and the size of the reaction site in the DNA chip coordinate system; The coordinates of the reaction sites on the DNA chip coordinate system are transformed into the coordinates on the printing coordinate system. The coordinates of the printing coordinate system are (X, Y, Z), where X and Y are the horizontal and vertical directions, and Z is the vertical direction. Obtain the resolution of the DNA inkjet printer in the X and Y directions; The coordinates of the reaction site in the printed coordinate system are converted to the coordinates in the pixel coordinate system by coordinate transformation, so as to determine the position and coverage of the reaction site in the pixel coordinate system. To obtain the coverage area of ​​the ink dots in the pixel coordinate system, where the ink dots are in rows E and columns F, let the spacing between ink dots in the X direction be DX and the spacing between ink dots in the Y direction be DY. Create a reaction site center position-ink dot printing template; the reaction site center position-ink dot printing template includes multiple position intervals, and a preset ink dot printing position corresponding to each position interval; the multiple position intervals include n×m position intervals, where n and m are natural numbers; During actual printing, select the preset ink dot printing position in the ink dot printing template based on the center position of the reaction site.

[0011] Preferably, the process of creating the reaction site center position-ink dot printing template includes the following steps: The multiple position intervals are divided as follows: In the pixel coordinate system, two ink dots are selected in the same row of ink dots in row E and column F. In the column corresponding to the two ink dots, one adjacent ink dot is selected in the same direction, for a total of 4 adjacent ink dots. The above four ink dots are used as endpoints to form a square with side lengths DX and DY. The offset step size in the Y direction is defined as PY, PY=DY / n, and the offset step size in the X direction is PX, PX=DX / m. This square is divided into the above n×m position intervals. For each position interval, denoted as (j, i), where i and j are natural numbers, i>=1, i<=n-1, j>=1, j<=m-1, the center of each position interval is taken as the center of the reaction site, the range of ink dots covered by the reaction site corresponding to each position space is obtained, and the preset ink dot printing position is obtained according to the number of ink dots required by the reaction site, denoted as MW(j, i).

[0012] Preferably, the process of creating the reaction site center position-ink dot printing template includes the following steps: If DY > DX, let m = 1; Set the distance between the center of the initial reaction site and one of the rows of ink dots to 0. Based on the number of ink dots required for the reaction site, obtain the preset ink dot printing position, denoted as MW(0). Let n>=2; For offset number i, the distance the center of the reaction site is shifted along the Y direction is denoted as d(i), where d(i) = PY*i; Based on the number of ink dots required for the reaction site, determine the set of ink dot printing positions MW(i) after translation, and obtain n sets of printing positions [MW(0), MW(1), ..., MW(n-1)].

[0013] Preferably, the process of creating the reaction site center position-ink dot printing template further includes: establishing the following position intervals: [0, PY / 2] or [d(n-1)+PY / 2, d(n-1)+PY], ..., [d(i)-PY / 2, d(i)+PY / 2], ...[d(n-1)-PY / 2, d(n-1)+PY / 2].

[0014] Preferably, DY is more than 3 times greater than DX.

[0015] Preferably, in the process of creating the reaction site center position-ink dot printing template: the preset ink dot printing position is obtained according to the number of ink dots required for the reaction site, including: selecting the preset ink dot printing position based on the principle of being as close as possible to the center position of the reaction site.

[0016] Preferably, the preset ink dot printing position is found by drawing circles with the center of the reaction site as the center and the diameter increasing from small to large.

[0017] Preferably, in the printing coordinate system, the X direction is parallel to the length direction of the DNA chip, and the Y direction is parallel to the width direction of the DNA chip.

[0018] Preferably, the DNA chip is a standard glass slide DNA chip.

[0019] The present invention also provides a DNA inkjet printing device that employs the adaptive printing data generation method described in any of the above claims.

[0020] This invention analyzes the positional relationship between reaction sites and ink dots, and uses sub-pixel offset to group the spacing between the center of the reaction site and the row and column ink dots to construct a template. By constructing a template, for reaction sites of the same size, only the center position of the reaction site needs to be obtained to directly obtain the preset ink dot printing position through the template, greatly reducing the amount of calculation and improving printing efficiency.

[0021] In this invention, when the spacing between ink dots in the Y direction of the DNA printing device is greater than the spacing in the X direction, the influence of ink dots in the X direction is ignored. Furthermore, by using sub-pixel offset, the spacing between the center of the reaction site and the row of ink dots is grouped to construct a template. By constructing this template, for reaction sites of the same size, only the center position of the reaction site needs to be obtained to directly obtain the predetermined ink dot position through the template, greatly reducing the computational load and improving printing efficiency. Attached Figure Description

[0022] Figure 1 This is a front view schematic diagram of a DNA chip, which is an exemplary embodiment of the present invention.

[0023] Figure 2 This is a partially enlarged schematic diagram of the DNA chip reaction sites, which is an exemplary embodiment of the present invention.

[0024] Figure 3 This is one of the schematic diagrams illustrating the positional relationship between the reaction site and the ink dot, which is an exemplary embodiment of the present invention.

[0025] Figure 4 for Figure 3 A magnified view of a portion of the image.

[0026] Figure 5 This is a second schematic diagram illustrating the positional relationship between the reaction site and the ink dot, which is an exemplary embodiment of the present invention.

[0027] Figure 6 This is one of the schematic diagrams illustrating the determination of a preset ink dot printing position based on the required number of ink dots, which is an exemplary embodiment of the present invention.

[0028] Figure 7 This is a second schematic diagram illustrating the determination of a preset ink dot printing position based on the required number of ink dots, as an exemplary embodiment of the present invention.

[0029] Figure 8 This is a third schematic diagram illustrating the determination of the preset ink dot printing position based on the required number of ink dots, which is an exemplary embodiment of the present invention.

[0030] Figure 9 This is a fourth schematic diagram illustrating the determination of the preset ink dot printing position based on the required number of ink dots, which is an exemplary embodiment of the present invention.

[0031] Figure 10 This is a schematic diagram showing the positional relationship between the reaction site and the ink dot, which is another exemplary embodiment of the present invention.

[0032] Figure 11 for Figure 10 A magnified view of a portion of the image.

[0033] Figure 12This is a schematic flowchart of an adaptive printing data generation method for a DNA inkjet printing device, which is an exemplary embodiment of the present invention.

[0034] Figure 13 This is a schematic diagram of the process for creating a reaction site center position-ink dot printing template, which is an exemplary embodiment of the present invention.

[0035] Figure 14 This is a schematic diagram of the process for creating a reaction site center position-ink dot printing template, which is another exemplary embodiment of the present invention.

[0036] Among them: 20-DNA chip, 21-reaction site. Detailed Implementation

[0037] The following description of embodiments of the present invention with reference to the accompanying drawings is intended to explain the overall inventive concept of the invention and should not be construed as a limitation thereof. In this invention, the same reference numerals denote the same or similar parts.

[0038] The features described herein may be implemented in various forms and should not be construed as limited to the examples described herein. Rather, the examples described herein are provided only to illustrate some of the many feasible ways in which the methods, apparatuses, and / or systems described herein will become clear upon understanding the disclosure of the invention.

[0039] The terminology used herein is for the purpose of describing various examples only and is not intended to limit disclosure. Unless the context clearly indicates otherwise, the singular form is intended to include the plural form as well. The terms “comprising,” “including,” and “having” indicate the presence of the described features, quantities, operations, components, elements, and / or combinations thereof, but do not preclude the presence or addition of one or more other features, quantities, operations, components, elements, and / or combinations thereof.

[0040] To enable those skilled in the art to utilize the content of this invention, the following exemplary embodiments may be provided in conjunction with specific application scenarios, specific systems, device and component parameters, and specific connection methods. However, these embodiments are merely examples for those skilled in the art, and the general principles defined herein can be applied to other embodiments and application scenarios without departing from the spirit and scope of this invention.

[0041] According to an exemplary embodiment of the present invention: Figures 1-14 As shown, the present invention provides an adaptive printing data generation method for a DNA inkjet printing device, wherein the DNA inkjet printing device uses a nozzle to spray ink droplets onto the reaction sites of a DNA chip, and the DNA chip has multiple circular reaction sites arrayed on it.

[0042] For example, such as Figures 1-2 The diagram illustrates commonly used DNA chips. Taking a glass slide-based DNA chip as an example, this type of DNA chip typically measures 75.3 mm in length and 25.3 mm in width. The reaction sites on it are extremely small; for example, a circular reaction site has a diameter of approximately 100-300 micrometers.

[0043] To achieve high-throughput detection or chemical DNA synthesis, a large number of reaction sites need to be integrated on the surface of a DNA chip. These reaction sites are typically arranged in a microarray, with each site being extremely small. In this invention, for example, the reaction region is designed as a circular reaction region with a diameter of 120 micrometers. Such a tiny size requires the use of high-precision technologies such as photolithography, precision printing, or laser processing during the manufacturing process to ensure the consistency of the shape, size, and spatial position of the reaction sites.

[0044] During DNA chip synthesis, the target monomer solution and activator solution required for each round of reactions are determined based on the target base sequence. For example, if the target base sequence is ATTC…G, the first round of reactions uses a monomer solution containing adenine (A), and the second round uses a monomer solution containing thymine (T). Each round involves spraying the nucleotide onto the reaction site through the nozzle of the synthesis apparatus, and so on. Following a defined target monomer solution, this process is repeated cyclically, with the nucleotide chain elongating by one base after each cycle. Through this cyclic reaction, the nucleotide chain can be gradually extended to synthesize the desired DNA sequence.

[0045] Because the reaction sites are very small, it is generally required that the solution be sprayed precisely to the center of the reaction site. Therefore, high-precision spraying is needed to improve the accuracy of the synthesis.

[0046] According to an exemplary embodiment of the present invention: Figures 1-14 As shown, an adaptive printing data generation method for a DNA inkjet printing device according to the present invention includes the following steps: obtaining the physical dimensions of the DNA chip, and the coordinates of the center of the reaction site and the size of the reaction site in the DNA chip coordinate system. For example, the DNA chip coordinate system typically has its origin at the lower left corner of the DNA chip, the length direction of the DNA chip as the X direction, and the width direction of the DNA chip as the Y direction.

[0047] The coordinates of the reaction sites in the DNA chip coordinate system are converted to those in the printing coordinate system through coordinate transformation. Since the DNA chip is located on a mounting base, the position of the base and the physical dimensions of the DNA chip are known. Therefore, the coordinates of the reaction sites in the DNA chip coordinate system can be converted to those in the printing coordinate system through coordinate transformation. In practice, preferably, after fixing the DNA chip on the mounting base, a calibration step can be included to obtain the precise position of the DNA chip. Calibration can be performed using the crosshairs on the DNA chip, which uses existing methods and will not be elaborated here. The coordinates of the printing coordinate system are (X, Y, Z), where X and Y are the horizontal and vertical directions, and Z is the vertical direction. Since the spray height is fixed, the Z-axis direction does not need to be transformed. That is, the position of the Z-axis is considered constant. For example, the X-direction of the printing coordinate system is parallel to the X-direction in the DNA chip coordinate system, the X-direction of the printing coordinate system is parallel to the Y-direction in the DNA chip coordinate system, and the Z-direction of the printing coordinate system is parallel to the Z-direction in the DNA chip coordinate system.

[0048] Obtain the resolution of the printing device in the X and Y directions. Transform the coordinates of the reaction site in the printing coordinate system to the pixel coordinate system, determining the position and coverage area of ​​the reaction site in the pixel coordinate system. After obtaining the resolution of the printing device in the X and Y directions, the coordinates of the reaction site in the printing coordinate system can be converted to pixel coordinates.

[0049] Obtain the coverage area of ​​the ink dots in the pixel coordinate system, with ink dots in rows E and columns F. Let the spacing between ink dots in the X direction be DX and the spacing between ink dots in the Y direction be DY.

[0050] By using the coordinate transformation described above, the distance between the center of the actual reaction site and its adjacent row of ink dots can be obtained, thus obtaining the range of ink dots covered by the reaction site.

[0051] like Figure 3 The diagram illustrates the positional relationship between a column of reaction sites (showing three) and ink dots on a DNA chip. The three large circles represent the three reaction sites, and the array of small circles indicates the ink dot printing positions. It is evident that the relative positional relationship between different reaction sites and ink dots within a column of reaction sites is different. If the preset ink dot printing position for each reaction site were determined by calculation based on the required number of ink dots, the computational workload would be extremely high.

[0052] According to an exemplary embodiment of the present invention: Figure 3 , Figure 4 , Figure 5 and Figure 13As shown, the process of creating the reaction site center position-ink dot printing template in this invention includes the following steps: assuming the spacing between ink dots in the X direction is DX and the spacing between ink dots in the Y direction is DY, where DY>DX; the above spacing is determined based on the resolution of the printing device in the X and Y directions.

[0053] like Figure 5 As shown schematically, the spacing between adjacent ink dots in the X direction is 5 micrometers, and the spacing between adjacent ink dots in the Y direction is 42.3 micrometers. It is evident that 42.3 micrometers is significantly larger than 5 micrometers, i.e., DY > DX. Therefore, the variation in the position of the reaction site in the X direction can be ignored. That is, when DY is significantly greater than DX, such as when DY is more than 3 times DX, preferably 4, 5, or 6 times DX, i.e. Figure 5 As shown, the ink dots within the reaction sites in the second row of the figure are roughly consistent, differing only at the edges. However, in practical applications, ink dots near the edges are not selected. Therefore, a template can be used, such as selecting the first one on the left as the template. When selecting four points, the four middle points of the middle row can be chosen, and all the above reaction sites can be applied. This method significantly reduces the computational load. Therefore, this invention preferably ignores the influence of the positional relationship between the reaction sites and ink dots in the X direction. A reaction site center position-ink dot printing template is created using the above method. The above method is more effective when DY is significantly larger than DX, such as when DY is more than three times DX.

[0054] like Figure 3 , Figure 4 As shown, a reaction site center position-ink dot printing template is created. The reaction site center position-ink dot printing template includes multiple position intervals and a preset ink dot printing position corresponding to each position interval. The multiple position intervals include n×m position intervals, where n and m are natural numbers. Let m=1; by setting m=1, the influence of the positional relationship between the reaction site and the ink dot in the X direction can be ignored. Preferably, the template includes the distance interval between the reaction site center position and its adjacent lower row ink dot, and the corresponding preset ink dot printing position within the aforementioned distance interval.

[0055] During actual printing, select the ink dot printing position in the ink dot printing template based on the center position of the reaction site. Specifically, the preset ink dot printing position can be determined based on the distance between the center position of the reaction site and the adjacent ink dot in the lower row.

[0056] As shown in Figures 3 and 4, Figure 13 As shown, the process of creating the reaction site center position-ink dot printing template includes the following steps: Set the distance between the center of the initial reaction site and one of the rows of ink dots to 0, and obtain the preset ink dot printing position according to the number of ink dots required for the reaction site, denoted as MW (0). Define the offset step size in the Y direction as PY, PY=DY / n, where n is a natural number, n>=2; The offset step size PY is smaller than both DX and DY, therefore, the above offset is also called sub-pixel offset.

[0057] For offset index i, the center of the reaction site is shifted by a distance d(i) along the Y direction, d(i) = PY*i, where i is a natural number, i>=1, i<=n-1). Determine the set of ink dot printing positions MW(i) after translation based on the number of ink dots required for the reaction site. For example, when i=1, the translation distance of the center is d(i)=PY*1, and the corresponding ink dot printing position set is MW(1). When i=2, the translation distance of the center is d(i)=PY*2, and the corresponding ink dot printing position set is MW(2). Similarly, when i=n-1, the translation distance of the center is d(i)=PY*(n-1), and the corresponding ink dot printing position set is MW(n-1).

[0058] Finally, we obtain n sets of printing positions [MW(0), MW(1), ..., MW(n-1)].

[0059] Based on the above process, the correspondence between the distance d(i) between the center of the reaction site and the ink dot and the preset printing position set is obtained. Subsequently, based on the distance relationship between the center of the reaction site and the ink dot, a suitable printing position can be directly found in the above template.

[0060] The following positional mapping relationship can be established schematically: [d0, d0+PY / 2] or [d(n-1)+PY / 2, d(n-1)+PY], ... [d(i)-PY / 2, d(i)+PY / 2] ... [d(n-1)-PY / 2, d(n-1)+PY / 2].

[0061] That is, if the distance between the center of the reaction site and the ink dot is in [d0, d0+PY / 2] or [d(n-1)+PY / 2, d(n-1)+PY], then MW(0) is selected; if it is in [d1-PY / 2, d1+PY / 2], then MW(1) is selected... and so on. If it is in [d(n-1)-PY / 2, d(n-1)+PY / 2], then MW(n-1) is selected.

[0062] If the above distance happens to be at the boundary point, such as d1+PY / 2, then since d1+PY / 2 is at the endpoint of both intervals, it can be selected forward or backward, i.e., MW(1) or MW(2).

[0063] For example, such as Figure 3 , Figure 4 The diagram illustrates a method for creating a printing template that centers the reaction site as an ink dot. Figure 3 As shown, the positional relationship between a column of reaction sites (three of which are illustrated) and ink dots on a DNA chip is illustrated. It can be seen that the relative positional relationship between different reaction sites and ink dots is different within a column of reaction sites. For rapid calculation, the reaction sites are classified according to their relative positions to the row of ink dots, and reaction site center position-ink dot printing templates are created. The spacing between the rows of ink dots is divided into 5 equal parts, resulting in five templates.

[0064] Set the distance between the center of the initial reaction site and one of the ink dots in a row to 0. Based on the number of ink dots required for the reaction site, obtain the preset ink dot printing position, denoted as MW(0). Of course, the distance between the center of the initial reaction site and any ink dot in the Y direction can also be set to 0, which is also within the protection scope of this invention. Define the offset step size in the Y direction as PY, where PY = DY / 5; For offset index i, the distance the center of the reaction site is shifted along the Y direction is denoted as d(i), where d(i) = PY*i, i is a natural number, i>=1, i<=n-1). That is: when i=1, the distance from the center of the reaction site to the row ink dot is PY, and the number of ink dots required according to the reaction site is obtained, and the preset ink dot printing position is obtained, which is MW (1). When i=2, the distance from the center of the reaction site to the row ink dot is 2*PY. Based on the number of ink dots required for the reaction site, the preset ink dot printing position is obtained and denoted as MW(2). And so on; when i=4, the number of ink dots required according to the reaction site is obtained, and the preset ink dot printing position is obtained, which is MW(4).

[0065] Establish the following position intervals: [0, PY / 2] or [9PY / 2, 5PY], [PY / 2, 3PY / 2], [3PY / 2, 5PY / 2], [5PY / 2, 7PY / 2], [7PY / 2, 9PY / 2].

[0066] The preset ink dot printing position is obtained from the template based on the distance between the center of the reaction site and the adjacent ink dot below it.

[0067] According to an exemplary embodiment of the present invention: to ensure the quality of DNA synthesis, the ink droplets should be as close as possible to the center of the reaction site during nozzle ejection. For example... Figures 6-9 The diagram illustrates how to preset the ink droplet printing position selection method based on the different ink droplet numbers required for the reaction site. Figures 6-9The units for both the x-axis and y-axis are micrometers. The exemplary reaction site is circular with a diameter of 120 micrometers. The spacing between adjacent ink dots in the X-direction is 5 micrometers, and the spacing between adjacent ink dots in the Y-direction is 42.3 micrometers.

[0068] like Figure 6 As shown, when a reaction site requires 9 ink dots, based on the principle of being as close as possible to the center of the reaction site, it is easy to select the 9 ink dots in the middle row of the diagram through manual observation. It should be noted that the above manual observation includes manual measurement using measuring tools such as a ruler. When a reaction site requires 17 ink dots, then... Figure 7 The ink dots shown are within the reaction sites. Select the middle 16 dots in the middle row and the middle 1 dot in the first row above.

[0069] One preferred method is to draw circles with the center of the reaction site as the center and the diameter increasing from small to large. For example, if the diameter of a reaction site is 120 micrometers, and 9 ink dots are needed, first draw a circle with a diameter of 20 micrometers and observe how many reaction sites are in the circle. If there are not enough, increase the diameter by 5 micrometers each time until a suitable preset ink dot position is selected.

[0070] Figure 8 The diagram illustrates the selection of preset ink dot positions when 9 ink dots are required: 4 dots in the middle for upward strokes and 5 dots in the middle for downward strokes. Figure 9 The diagram illustrates the selection of preset ink dot positions when 17 ink dots are needed: the middle 8 dots are used for the upward stroke, and the middle 9 dots are used for the downward stroke. The selection is based on the principle of being as close as possible to the center of the reaction site, and will not be repeated here.

[0071] According to an exemplary embodiment of the present invention: Figure 10 and Figure 11 The diagram illustrates another preferred method for fabricating a reaction site center position-ink dot printing template according to the present invention, as shown below. Figure 10 As shown, when DX and DY are not significantly different, the change in the X direction should no longer be ignored. Figure 10 It can be seen that the different positions of the reaction sites in the second row will result in different printing positions of the selected preset ink dots.

[0072] The reaction site center position-ink dot printing template is created in the following way: The reaction site center position-ink dot printing template includes multiple position intervals and a preset ink dot printing position corresponding to each position interval; the multiple position intervals include n×m position intervals, where n and m are natural numbers.

[0073] The above multiple position intervals are divided in the following way: In the pixel coordinate system, select two ink dots in the same row of ink dots in row E and column F. In the column corresponding to the two ink dots, select one adjacent ink dot in the same direction, for a total of 4 adjacent ink dots. With the above four ink dots as endpoints, they form a square with side lengths DX and DY. Define the offset step size in the Y direction as PY, PY=DY / n, and the offset step size in the X direction as PX, PX=DX / m. Divide it into n×m position intervals, where n and m are natural numbers.

[0074] For each position interval, denoted as (j, i), where i and j are natural numbers, i>=1, i<=n-1, j>=1, j<=m-1, the center of each position interval is taken as the center of the reaction site, the range of ink dots covered by the reaction site corresponding to each position space is obtained, and the preset ink dot printing position is obtained according to the number of ink dots required by the reaction site, denoted as MW(j, i).

[0075] In subsequent applications, the preset ink dot printing position is determined based on the center of the reaction site and its location within the interval.

[0076] like Figure 11 As shown, it is assumed that the center of the reaction site is located at Figure 11 For the cross-shaped area, the corresponding preset ink dot position in MW(i,j) is selected. If it is located at the boundary, the preset ink dot position corresponding to any interval adjacent to the boundary can be selected, which will not be elaborated here.

[0077] This invention analyzes the positional relationship between reaction sites and ink dots, and uses sub-pixel offset to group the spacing between the center of the reaction site and the row and column ink dots to construct a template. By constructing a template, for reaction sites of the same size, only the center position of the reaction site needs to be obtained to directly obtain the preset ink dot printing position through the template, greatly reducing the amount of calculation and improving printing efficiency.

[0078] In this invention, when the spacing between ink dots in the Y direction of the DNA printing device is greater than the spacing in the X direction, the influence of ink dots in the X direction is ignored. Furthermore, by using sub-pixel offset, the spacing between the center of the reaction site and the row of ink dots is grouped to construct a template. By constructing this template, for reaction sites of the same size, only the center position of the reaction site needs to be obtained to directly obtain the predetermined ink dot position through the template, greatly reducing the computational load and improving printing efficiency.

[0079] It should be noted that, although in the example of this invention, the X direction is the stepping direction and the Y direction is the length direction of the nozzle, the above directions can obviously be interchanged, that is, the X direction is the length direction of the nozzle and the Y direction is the stepping direction, both of which are within the protection scope of this invention.

[0080] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that variations and combinations of elements may be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An adaptive printing data generation method for a DNA inkjet printing device, wherein the DNA inkjet printing device uses a nozzle to spray ink droplets onto the reaction sites of a DNA chip, the DNA chip having an array of multiple reaction sites, characterized in that: Includes the following steps: Obtain the physical dimensions of the DNA chip, as well as the coordinates of the center of the reaction site and the size of the reaction site in the DNA chip coordinate system; The coordinates of the reaction sites on the DNA chip coordinate system are transformed into the coordinates on the printing coordinate system. The coordinates of the printing coordinate system are (X, Y, Z), where X and Y are the horizontal and vertical directions, and Z is the vertical direction. Obtain the resolution of the DNA inkjet printer in the X and Y directions; The coordinates of the reaction site in the printed coordinate system are converted to the coordinates in the pixel coordinate system by coordinate transformation, so as to determine the position and coverage of the reaction site in the pixel coordinate system. To obtain the coverage area of ​​the ink dots in the pixel coordinate system, where the ink dots are in rows E and columns F, let the spacing between ink dots in the X direction be DX and the spacing between ink dots in the Y direction be DY. Create a reaction site center position-ink dot printing template; the reaction site center position-ink dot printing template includes multiple position intervals, and a preset ink dot printing position corresponding to each position interval; the multiple position intervals include n×m position intervals, where n and m are natural numbers; During actual printing, select the preset ink dot printing position in the ink dot printing template based on the center position of the reaction site.

2. The adaptive print data generation method according to claim 1, characterized in that: Creating a center position ink dot printing template for reaction sites involves the following steps: The multiple position intervals are divided as follows: In the pixel coordinate system, two ink dots are selected in the same row of ink dots in row E and column F. In the column corresponding to the two ink dots, one adjacent ink dot is selected in the same direction, for a total of 4 adjacent ink dots. The above four ink dots are used as endpoints to form a square with side lengths DX and DY. The offset step size in the Y direction is defined as PY, PY=DY / n, and the offset step size in the X direction is PX, PX=DX / m. This square is divided into the above n×m position intervals. For each position interval, denoted as (j, i), where i and j are natural numbers, i>=1, i<=n-1, j>=1, j<=m-1, the center of each position interval is taken as the center of the reaction site, the range of ink dots covered by the reaction site corresponding to each position space is obtained, and the preset ink dot printing position is obtained according to the number of ink dots required by the reaction site, denoted as MW(j, i).

3. The adaptive print data generation method according to claim 1, characterized in that: Creating a center position ink dot printing template for reaction sites involves the following steps: If DY > DX, let m = 1; Set the distance between the center of the initial reaction site and one of the rows of ink dots to 0. Based on the number of ink dots required for the reaction site, obtain the preset ink dot printing position, denoted as MW(0). Let n>=2; For offset number i, the distance the center of the reaction site is shifted along the Y direction is denoted as d(i), where d(i) = PY*i; Based on the number of ink dots required for the reaction site, determine the set of ink dot printing positions MW(i) after translation, and obtain n sets of printing positions [MW(0), MW(1), ..., MW(n-1)].

4. The adaptive print data generation method according to claim 3, characterized in that: The process of creating the reaction site center position-ink dot printing template also includes: establishing the following position intervals: [0, PY / 2] or [d(n-1)+PY / 2, d(n-1)+PY], ..., [d(i)-PY / 2, d(i)+PY / 2], ..., [d(n-1)-PY / 2, d(n-1)+PY / 2].

5. The adaptive print data generation method according to claim 3, characterized in that: DY is more than 3 times that of DX.

6. The adaptive print data generation method according to any one of claims 2-5, characterized in that: In the process of creating the center position of the reaction site - ink dot printing template: based on the number of ink dots required for the reaction site, the preset ink dot printing position is obtained, including: selecting the preset ink dot printing position according to the principle of being as close as possible to the center position of the reaction site.

7. The adaptive print data generation method according to claim 6, characterized in that: The preset ink dot printing position is found by drawing circles with the center of the reaction site as the center and the diameter increasing from small to large.

8. The adaptive print data generation method according to any one of claims 1-5, characterized in that: In the printing coordinate system, the X direction is parallel to the length direction of the DNA chip, and the Y direction is parallel to the width direction of the DNA chip.

9. The adaptive print data generation method according to any one of claims 1-5, characterized in that: The DNA chip is a standard glass slide DNA chip.

10. A DNA inkjet printing device, characterized in that: The adaptive print data generation method described in any one of claims 1-9 is adopted.

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