KR101257847B1 - Device for printing droplet on a substrate and a method for printing droplet on it - Google Patents

Abstract

The present invention provides a solution on a substrate having an improved structure so that the volume of the solution droplet is maintained at a predetermined volume so that the solution including the bioparticles and the like can be accurately dropped to a desired size in a target portion at a desired position of the substrate. It relates to an apparatus for printing.

A needle-shaped solution droplet generating member which is arranged in a vertical direction and has a receiving part for receiving a solution, and a discharge hole connected to the receiving part and formed at a lower end of the receiving part so that the solution is discharged to the outside of the receiving part; A substrate disposed below the droplet generating member and having a target portion to which a solution discharged from a discharge port of the droplet generating member is attached to the substrate; A voltage applying device for applying a force to the droplets generated in the discharge port and causing the solution drop to fall to the target portion of the substrate; volume measuring means for measuring a volume of the solution droplet protruding downward from the discharge port; And solution control means for maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured by the volume measuring means.

Biochip, DNA microarray, bioparticles, printing, electric charge concentration phenomenon, electric charge concentration, volumetric means, solution control means, coulomb force, electrophoretic force, dielectric force, open voltage application device

Description

Device for printing droplet on a substrate and a method for printing droplet on it}

1 is a schematic cross-sectional view of an apparatus for printing a solution on a substrate using an electric charge concentration phenomenon according to a preferred embodiment of the present invention.

2 to 3C are two-dimensional images of the droplets detected by the image sensor in the process of dropping the solution onto the substrate using the printing apparatus shown in Figure 1 and the principle of measuring the volume of the droplets from the image A diagram for explaining.

FIG. 4 is a flow chart showing an algorithm for adjusting the volume of the droplet based on the volume calculation of the droplet and the volume performed in the computer processing apparatus in the printing apparatus shown in FIG. 1.

5 to 7 is a view showing a volume change with time of the solution droplet formed in the discharge port in the process of dropping the solution on the substrate using the printing device shown in FIG.

FIG. 8 is a graph showing the intensity of each printed spot after printing the solution onto the substrate using the printing device shown in FIG. 1.

FIG. 9 is a photograph of scanning each printed spot after printing the solution on the substrate using the printing apparatus shown in FIG. 1.

FIG. 10 illustrates the relationship between the positive charges charged in the field forming electrode and the negative charges induced on the substrate by the positive charges when the voltage is applied to the printing apparatus shown in FIG. Figure is a schematic diagram.

11 is a schematic cross-sectional view of an apparatus for printing a solution using an electric charge concentration phenomenon according to another embodiment of the present invention.

12 is a schematic cross-sectional view of an apparatus for printing a solution using an electric charge concentration phenomenon according to another embodiment of the present invention.

<Description of the symbols for the main parts of the drawings>

10 ... droplets of biological particles 20 ... field forming electrode

21 ... electrode lead wire 22 ... receiving part

23 Discharge outlet 30 Substrate

31.Target 40 ... Printer body

50 ... Open voltage applying device 60,61 ... Light source

62 Divergence Lens 63 Image Sensor

64 Computer processing unit 66 Pump

100,200,300 ... A device for printing a solution on a substrate using an electric charge concentration phenomenon

641 input unit 64 2 control unit

643.Output CL ... section

The present invention relates to an apparatus for printing a solution on a substrate and an apparatus for printing ink on a printing paper, and more particularly, nucleic acids such as probe DNA, RNA, peptide nucleic acid (PNA), and LNA. Droplets of bioparticles such as proteins, oligopeptides, human cells, animal cells, plant cells, viruses, bacteria, etc. In order to produce biochips by immobilization, a device for printing droplets of bioparticles on a substrate by using an electric charge concentration phenomenon and an ink charge are dropped onto a printing paper to print the contents of a computer document file and a photo file. The present invention relates to an apparatus for printing ink on printing paper.

Along with the phenomenal progress of the Human Genome Project, there has been a great need for a way to rapidly provide vast amounts of genetic information in the diagnosis, treatment and prevention of genetic diseases. Sanger's method, which has been used as a sequencing method until then, has been steadily developed because of the development and automation of a polymerase chain reaction (PCR) method that replicates DNA. Because of the time, effort, cost, and high level of proficiency, large amounts of genes cannot be analyzed, and new sequencing systems are constantly being sought. The need for this age has made progress in many areas related to the manufacturing and use of biochips over the last few years.

Biochip is a method for analyzing gene expression patterns, gene defects, protein fragments, and various reaction patterns by binding bioparticles such as nucleic acids, proteins, and cells to solid substrate surfaces such as silicon, surface modified glass, polypropylene, and activated polyacrylamide. Biological Microchip that can be.

When the target material to be analyzed is reacted with the biochip, the target material is combined with the probes attached to the biochip, and the target material can be analyzed by observing and interpreting the optical material or radiochemical method. . For example, when a target DNA fragment to be analyzed is bound to a DNA chip (DNA microarray) to which a probe DNA is attached, different hybridization bonds are determined depending on the complementary degree of the sequences on the probe and the target DNA fragment. (hybridization) state is achieved, and the sequencing by hybridization (SBH) can be analyzed by observing and interpreting it through various detection methods.

In the printing apparatus used to fabricate such a biochip or DNA micro array, a droplet generating member for generating a droplet above the substrate for dropping a solution on the substrate exists, and below the droplet generating member. Protruding droplets are evaporated in proportion to their surface area, so that the volume of the droplets decreases over time. As such, if the volume of the droplets is reduced, the spot size of the droplets to be printed on the substrate is also reduced. However, in the case of maintaining a spot having a constant size, there is a problem in that a device for maintaining a constant size of the droplet does not exist in the related art and thus cannot obtain a desired spot size.

In the fabrication of the biochip or DNA microarray, since droplets are dropped on the substrate to form spots, the size of the droplets has a great influence on the spot size formed on the substrate. Therefore, in order to manufacture a microarray consisting of spots of a constant size, it is necessary to maintain the solution droplets formed at the lower portion of the solution generation member at a constant size. If the size of the droplets formed at the lower portion of the droplet generating member is not kept constant, the size of the spots formed on the substrate is not constant. As a result, DNA micro-structures must be subjected to precise analysis such as sequencing. There is a problem that the purpose of the array cannot be achieved.

The present invention has been made to solve the above problems, an object of the present invention, by using an electric charge concentration phenomenon is improved structure to maintain a predetermined volume of the solution droplets protruding to the outside of the discharge port To provide a device for printing a solution on a substrate.

In addition, another object of the present invention is to provide a printing method capable of printing a solution containing bioparticles, ink and the like on a substrate with a constant spot size by using an electric charge concentration phenomenon.

In order to achieve the above object, an apparatus for printing a droplet on a substrate according to the present invention, which is arranged long in the vertical direction, is connected to the receiving portion containing the solution, the receiving portion and the solution is received A needle-shaped solution droplet generating member having a discharge port formed at a lower end of the receiving portion so as to be discharged to the outside of the portion;

A substrate disposed below the droplet generating member and having a target portion to which a solution discharged from a discharge port of the droplet generating member is attached to the substrate;

A voltage applying device for applying a force to the droplets generated at the discharge port and causing the droplets to fall to the target portion of the substrate;

Volume measuring means for measuring a volume of a droplet formed by protruding downwardly from the discharge port; And

And a solution adjusting means for maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured by the volume measuring means.

According to the invention, the principle of printing the droplets generated in the discharge port on the substrate is preferably using the electric charge concentration (electric charge concentration) phenomenon.

According to the present invention, the droplet generating member is made of a conductive material, and is arranged long in the vertical direction, the receiving portion for receiving the solution, and is connected to the receiving portion so that the solution is discharged to the outside of the receiving portion It is preferable that it is a needle-shaped field formation electrode which has the discharge port formed in the lower end part of the accommodating part.

The voltage applying device is electrically connected to the field forming electrode to charge the field forming electrode, and is applied to a force generated between the charge charged in the field forming electrode and the charge induced in the substrate by the charge. It is preferable that the solution is an open voltage application device that causes the solution to fall to the target portion of the substrate.

According to the invention, the volume measuring means, the light source for shining a light beam on the solution formed below the discharge port; An image sensor detecting a shadow image of the droplet generated by the light source; And a computer processing device which receives data sensed by the image sensor and calculates a volume of the droplet.

In addition, according to the present invention, it is preferable that a lens is disposed between the light source and the image sensor.

In addition, according to the present invention, the image sensor is preferably able to detect the one-dimensional image or two-dimensional image of the droplet.

In addition, according to the present invention, the light source is preferably disposed perpendicular to the longitudinal direction of the field-forming electrode.

In addition, according to the present invention, the solution control means preferably comprises a pump for pressurizing or reducing the contained solution of the receiving portion.

In addition, according to the present invention, the pump is preferably a syringe pump.

Further, according to the present invention, the substrate is an electrical insulator that is not grounded,

The lower side of the substrate is preferably an air layer so as not to affect the electric field by the open voltage application device.

In addition, according to the present invention, the solution comprises a bioparticle, the bioparticle is preferably selected from the group consisting of nucleic acids, proteins, oligopeptides, sugars, eukaryotic cells, viruses and bacteria.

In addition, according to the present invention, it is preferable that the open voltage applying device is configured to apply a pulse voltage having a pulse shape so that an intermittent electric field is formed between the field forming electrode and the substrate.

In addition, according to the present invention, it is preferable that a pulse voltage of 100V to 100,000V is applied to the field forming electrode.

In addition, according to the present invention, it is preferable that the pulse width of the pulse voltage is 10 Hz to 100 Hz.

Further, according to the present invention, the pulse shape of the pulse voltage is preferably trapezoidal.

In addition, according to the present invention, the substrate is preferably made of one or more selected from the group consisting of silicon, glass, and polymer.

In addition, according to the present invention, the surface of the substrate is a amine group, a carboxyl group, biotin, streptavidin (streptavidine), poly-L-lysine and At least one member selected from the group consisting of thiols is preferably coated.

In addition, in order to achieve the above object, in the method of printing a solution on a substrate using an electric charge concentration phenomenon, it is made of a conductive material, the accommodation containing a solution containing the bioparticles, etc. A field forming electrode arrangement step of disposing a needle-shaped field forming electrode having a discharge hole formed at a lower end portion of the accommodating part and connected to the accommodating part and discharging the solution to the outside of the accommodating part; A substrate disposing step of having a target portion to which a solution including bioparticles discharged from a discharge hole of the field forming electrode is attached and separated, and placing a substrate under the field forming electrode; Arranging an open voltage applying device for arranging an open voltage applying device electrically connected to the field forming electrode; Probe DNA, RNA, PNA (Peptide nucleic acid), LNA, etc. Nucleic acid: Antigen, Antibody, etc. Proteins: Oligopeptides: Sugars: Human cells, animal cells, plant cells Eukaryotic cell types such as; virus; A solution supplying step of supplying a solution containing bioparticles such as bacteria to a receiving portion of the field forming electrode; A volume measuring step of measuring a volume of a droplet formed by protruding downwardly from the discharge port; A solution adjusting step of maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured by the volume measuring means; And applying a voltage to the field forming electrode from the open voltage applying device to charge the field forming electrode, and the solution by the force generated between the charged charge and the charge induced in the substrate by the charge. It characterized in that it comprises a solution printing step of dropping to the target portion of the substrate.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is a cross-sectional view schematically showing an apparatus for printing a solution on a substrate using an electric charge concentration phenomenon according to an embodiment of the present invention, Figures 2 to 3c using the printing device shown in FIG. In the process of dropping the solution on the substrate, it is a view for explaining the principle of measuring the volume of the droplet from the image and the two-dimensional image of the droplet detected by the image sensor, Figure 4 is the printing shown in FIG. A flow chart showing an algorithm for adjusting the volume of a droplet based on the volume calculation of the droplet and the volume of the solution performed by the computer processing apparatus in the apparatus, and FIGS. FIG. 8 is a view illustrating a volume change with time of a solution drop formed in the discharge hole in the process of dropping a solution. After printing a solution on a substrate using a printed printing device, a graph showing the intensity of each printed spot is shown, and FIG. 9 is a diagram of printing a solution on a substrate using the printing device shown in FIG. 1. Afterwards, it is a photograph of scanning each printed spot.

1 to 9, the apparatus 100 for printing a solution 10 on a substrate using the electric charge concentration phenomenon of the present embodiment includes a field forming electrode 20, a substrate 30, and a printer body. 40, an open voltage application device 50, a volume measuring means, and a solution adjusting means.

The field forming electrode 20 may be formed of a conductive metal such as gold, platinum, copper, or the like, or a conductive polymer, any one of indium-tin oxide (ITO) GLASS, carbon nanotubes, or the like. , Conductive polymer, and ITO (Indium-Tin Oxide) GLASS, at least two of the carbon nanotubes, in this embodiment is made of stainless steel (stainless steel). The field forming electrode 20 is elongated in one direction, and is generally needle-shaped, and is long in the vertical direction. An electrode lead line 21 is connected to an upper end of the field forming electrode 20, and the electrode forming line 21 electrically connects the field forming electrode 20 to an open voltage applying device 50 described later. It is.

The field forming electrode 20 includes a receiving portion 22 and a discharge port 23.

The accommodating part 22 is a probe DNA, RNA, PNA (Peptide nucleic acid), LNA, such as nucleic acids (nucleic acid), antigens, antibodies such as antibodies (Protein), oligopeptides, human cells, It is a part that contains a solution containing bioparticles or inks such as cells such as animal cells and plant cells, viruses and bacteria.

The discharge port 23 is formed at the lower end of the accommodating part 22 and is connected to the accommodating part 22. Since the inner diameter of the discharge port 23 is formed to be very small, if the force is not applied from the outside, the solution 10 overcomes gravity by the surface tension and is suspended in the discharge port 23. The solution 10 accommodated in the accommodating portion 22 through the discharge port 23 may be discharged to the outside of the accommodating portion 22 by the electric charge concentration phenomenon described later. Since the vicinity of the discharge port 23 is hydrophobic, the contact angle of the solution 10 is increased so that the solution 10 does not flow next to the discharge port 23.

The substrate 30 constitutes a biochip or DNA microarray, and is made of any one of an electrical insulator, glass, or a polymer, or at least two of silicon, glass, and a polymer. In this embodiment, an amine (Amine) It consists of coated glass. The lower side of the substrate is a stage made of a conductor such as a metal so that electromagnetic interaction with the field forming electrode 20 does not occur electrically so as not to affect the electric field by the open voltage application device 50 described later. It is comprised so that it may become an air layer, without using it. The substrate 30 is disposed below the field forming electrode 20, and is particularly arranged to be substantially orthogonal to the field forming electrode 20. A target portion is formed on the substrate 30. The solution 10 discharged from the discharge port 23 of the field forming electrode 20 is attached to the target portion. The substrate 30 is not grounded. The surface of the substrate 30, in particular the target portion of the substrate is coated with any one of an amine group, a carboxyl group, streptavidin, biotin, thiol, poly-L-Lysine Or coated with at least two of an amine group, a carboxyl group, streptavidin, biotin, thiol, and poly-L-Lysine. Less can be attached to the surface of the substrate better. The substrate 30 may be installed on a stage (not shown) and moved by a conveyor or the like.

The printer body 40 is disposed above the discharge port 23 of the field forming electrode 20. The printer body 40 supports the field forming electrode 20 and is made of PMMA (polymethlymethacrylate). The printer body 40 is capable of three-dimensional movement in the x, y and z axis by a separate driving device (not shown). Thus, by driving the separate driving device it is possible to move the field forming electrode 20 supported by the printer body 40 above the target portion to be spaced apart from the target portion by a certain distance.

The open voltage application device 50 is electrically connected to the field forming electrode 20. The open voltage applying device 50 may apply a pulsed voltage to the field forming electrode 20 through the electrode lead line 21. When the pulse voltage is applied, an electric field is intermittently formed between the field forming electrode 20 and the substrate 30. That is, at the moment when the electric field is formed between the field forming electrode 20 and the substrate 30, the droplet 10a is dropped from the discharge port 23 to the substrate 30 so that the solution on the substrate 30 The spot of the droplet 10a is formed. If the pulse interval of the pulse voltage is shortened, a large number of spots are formed per unit time, and if the pulse interval is long, a relatively small number of spots are formed per unit time.

On the other hand, it is preferable that a voltage of 100V to 100,000V is applied to the field forming electrode. In particular, it is more preferable that the pulse width of the pulse voltage is 10 Hz to 100 Hz. When applying a pulse voltage outside the voltage range and the pulse width as described above, by applying a Coulomb force (Fe) of the appropriate size to the droplet 10, the droplet 10 is efficiently applied to the substrate 30 It is not preferable because it cannot be dropped. The pulse shape of the pulse voltage is preferably trapezoidal. If the pulse shape is trapezoidal, the solution droplet 10a formed at the discharge port 23 is clearly distinguished from the moment when the electric field is formed between the field forming electrode 20 and the substrate 30. The efficiency of spots falling to the substrate 30 increases.

The volume measuring means includes a light source 60, an image sensor 63, and a computer processing device 64.

The light source 60 is provided to shine a light beam on the droplet 10a formed at the lower portion of the discharge port 23. The droplet 10a has a shadow image by the light source 60. The light source 60 is disposed to emit light in a direction substantially perpendicular to the longitudinal direction of the field forming electrode 20. As the light source 60, a general incandescent lamp or a light emitting diode (LED) may be used.

The image sensor 63 is provided to detect a shadow image of the droplet 10a generated by the light source 60. The image sensor 63 is a semiconductor device that converts an optical image into an electrical signal, and a representative example thereof is a charge coupled device (CCD). A CCD image sensor is a device in which charge carriers are stored in capacitors and carriers are stored while individual metal-oxide-silicon (MOS) capacitors are in close proximity to each other. The image sensor 63 is well known as the CCD and detailed description thereof will be omitted.

The image sensor 63 may detect a shadow image of the droplet 10a in two or one dimensions. That is, since the shape of the solution 10a is generally a part of a sphere, the height of the solution 10a has a correlation proportional to the volume of the solution 10a, so that the height of the solution 10a is increased. When detected, the volume of the solution 10a can be calculated. The image sensor 63 for this purpose is a one-dimensional image sensor (63). On the other hand, in general, when using the two-dimensional image sensor 63, the shadow image of the droplet (10a) by measuring the diameter of the circular cross-section according to the height to calculate the area of the circular cross-section and the height of the droplet The volume of the droplet 10a can be obtained by integrating the area of the circular cross section with respect to the. In this embodiment, the two-dimensional image sensor 63 is employed. A diverging lens 62 is disposed between the image sensor 63 and the light source 60 to enlarge the shadow image of the droplet 10a. Since the size of the droplet 10a is too small, the diverging lens 62 is provided to enlarge the shadow image of the droplet 10a to increase the detection yield of the image sensor 63. The diverging lens 62 typically includes a concave lens that emits incident light.

The computer processing device 64 is provided to calculate the volume of the droplet 10a and generate an output signal for driving the pump 66, which will be described later, in comparison with the volume of the predetermined droplet 10a. .

The computer processing device 64 includes an input unit 641, a control unit 642, and an output unit 643. The input unit 641 receives a portion of the shadow image of the droplet 10a from the image sensor 63.

The controller 642 calculates the volume of the droplet 10a from the data of the shadow image of the droplet 10a received from the input unit 641 and generates an output signal of the pump 66 to be described later. That's the part. The controller 642 calculates the volume of the droplet 10a by an algorithm as described below. The principle of calculating the volume of the droplet 10a in the control unit 642 is as follows.

That is, FIG. 2 schematically shows an example of the shadow image of the solution 10a and the concept of integrating an arbitrary cross section at an arbitrary position. FIG. 3a shows the profile of the contrast of the image for any section line CL such that the cross-section of the droplet 10a is circular at a particular location of the droplet 10a. The profile for the image contrast can distinguish the boundary of the solution droplet 10a by the difference in contrast according to the position. Meanwhile, to differentiate the boundary of the solution droplet 10a more finely, as shown in FIG. 3B, when the image profile according to the contrast is differentiated with respect to time, peaks and peaks at the boundary of the solution droplet 10a are different. Since a valley occurs on the graph, the distance between the peak and the valley becomes the width of the dark part of the image, which is the diameter of the circular section (2R). 3c shows the diameter 2R of the circular cross section according to the position of the solution droplet 10a thus obtained. Therefore, the cross-sectional area (πR ² ) of the circular cross-sections can be calculated. In this way, the area of the circular cross section is calculated while moving the section line CL from the lower end of the discharge port 23 to the lower end of the solution 10, and the original cross sectional areas are calculated with respect to the height of the solution drop 10a. When integrated, the solution becomes the volume of the droplet 10a.

The process performed by the controller 642 using this principle will be described in more detail as follows. Referring to the flowchart shown in FIG. 4, an image of the droplet 10a is obtained from the image sensor 63. The image is input to the controller 642 through the input unit 641. The controller 642 obtains the diameter of the circular cross section from the section line CL as shown in FIG. 4 at each pixel while moving the image along the height of the droplet 10a by pixel. The circular cross-sectional area is found by After that, the position is moved to the next pixel and the same process is repeated, and the circular cross-sectional areas are summed together to calculate the volume of the droplet 10a. The volume of the solution droplets 10a measured in this way is compared with a preset volume. If the volume of the measured solution 10a is smaller than the volume of the solution 10a, the pump 66, which will be described later, generates a signal for applying pressure to the solution 10 contained in the receiving portion 22. Let's do it. Therefore, the volume of the solution 10a is increased. On the other hand, if the volume of the measured solution droplet (10a) is larger than the volume of the set solution (10a) the pump 66 to be described later to reduce the pressure to the solution 10 contained in the receiving portion 22 Generate. Therefore, the volume of the solution 10a is reduced. While repeatedly performing such an algorithm, the volume of the solution 10a is maintained at a predetermined volume.

The output unit 643 is a portion for sending the control signal of the pump 66 generated by the control unit 642 to the pump 66.

The solution adjusting means includes a pump 66. The pump 66 is preferably a syringe pump, for example. The syringe pump is a variable flow pump capable of supplying a small amount of reagent at a constant flow rate or rapidly. The syringe pump includes a high resolution micro stepping motor, the structure of which is well known, and thus the detailed description thereof will be omitted. The pump 66 receives a drive signal from the output portion 643 of the computer processing device 64 and protrudes below the discharge port 23 by pressurizing or depressurizing the solution 10 contained in the accommodating portion 22. It is intended to increase or decrease the volume of the droplet 10a formed.

Hereinafter, an example of a process of printing the solution 10 using the apparatus 100 for printing a solution containing bioparticles or ink on a substrate using the electric charge concentration phenomenon of the present embodiment will be described in detail. .

First, the driving device is driven to move the printer body 40, on which the field forming electrode 20 is supported, above the target portion of the substrate 30. Subsequently, nucleic acids such as probe DNA, RNA, PNA (Peptide nucleic acid), and LNA: proteins such as antigens and antibodies: oligopeptides: sugars: human cells, animal cells Eukaryotic cells such as plant cells; virus; The solution 10 including the bioparticles such as bacteria is supplied to the receiving portion 22 of the field forming electrode 20.

After supplying the solution 10 in this way, when the pulse voltage having a pulse width of 10V to 100V in the trapezoidal shape of 100V to 100,000V is applied to the field forming electrode 20 by the open type voltage applying device 50, The solution drop (10a) hanging on the (23) is filled with a positive charge, thereby inducing a negative charge on the substrate (30). An electric field is formed between the positive and negative charges as shown in FIG. 10.

As such, when the positive charge is filled in the droplet 10a and thus negative charge is induced in the portion of the substrate 30 facing the droplet 10a, a coulomb force is generated between the positive charge and the negative charge. . Since the negative charge is induced below the solution 10a, the coulombic force acts intensively under the solution 10a. When the droplets hanging on the discharge port 23 by the coulomb force flow down to the substrate 30 in a conical form to form a spot, the positive charges charged in the droplets 10a together with the negative charge of the substrate. It will be extinguished, thereby reducing the Coulomb force. That is, the coulombic force used to pull the droplets hanging from the discharge port 23 downward is reduced. As such, since the charge charged in the solution disappears, the coulomb force is reduced, and thus, the solution drops protrude from the lower portion of the discharge port 23.

In this process, although the droplet 10a protruding from the lower end of the discharge hole is a short time, the volume of the droplet 10a is gradually reduced by evaporation. However, as in the present invention, the volume measuring means and the solution adjusting means may maintain the volume of the solution droplet 10a formed by protruding at the lower end of the discharge port 23 with the volume of the predetermined solution droplet 10a. It has an effect.

As described above, in order to quantitatively confirm that the droplet 10a can be maintained at a constant size unlike the conventional example, the volume of the solution is set to 8nl, 10nl, and 12nl, respectively, DNA having a sequence of NH ₂ -C ₆ -tgttctcttgtcttg 3 'on a substrate coated with an amine using the apparatus 100 for printing a solution on a substrate using the above-described electric charge concentration phenomenon according to the present invention An experiment was performed to print the solution. When the hybridization reaction was performed using a DNA having a target sequence of Cy ₃ -C ₆ -caagacaagagaaca 3 ′, the spot pattern as shown in FIG. 9 was obtained. The spot pattern shown in FIG. 9 is a picture scanned with an Axon scanner, and the spot intensity for this spot pattern is as shown in FIG. 8.

In addition, while the volume measuring means and the solution control means is operated, the volume change of the measured solution droplet (10a) is shown in Figs. 5 is a case where the volume of the solution 10a is set to 8 nl, FIG. 6 shows a case where 10 nl and FIG. 7 are set to 12 nl. As can be seen in Figures 5 to 7 it can be seen that the volume of the solution is maintained at the set volume within the error range 0.14nl.

On the other hand, in another embodiment of the present invention shown in Figure 11, the apparatus 200 for printing a solution on a substrate by using the electric charge concentration phenomenon, using a laser light source as the light source 61, the laser light source Since the light beam irradiated at is strong in straightness, in order to form the shadow image of the solution drop 10a, the light beam is emitted to the solution drop 10a by using a diverging lens 62 so as to be emitted as a general illumination. A diverging lens 62 is disposed between the laser light source and the droplet 10a.

On the other hand, in another embodiment of the present invention shown in Figure 12, the device 300 for printing a solution on the substrate using the electric charge concentration phenomenon, the solution droplet (10a) serves as a diverging lens 62 The light source 60 is disposed above the accommodating part 22 so that the substrate 30 is made of a transparent material, and the image sensor 63 is positioned below the substrate 30. Placed. Since other components are the same, a detailed description thereof will be omitted and reference will be made to the above-described preferred embodiment of the present invention.

Meanwhile, in the above embodiments, only the apparatus for printing a solution containing mainly bioparticles on the substrate 30 will be described. However, when the above-described electric charge concentration phenomenon is used, the biomaterial on the substrate 30 may be used. Similar to an apparatus for printing a solution containing particles, an apparatus for printing ink on printing paper or a printing substrate may be configured. In addition, by using the electric charge concentration phenomenon, the printing ink may be dropped onto the glass substrate for the color filter or the like to manufacture the color filter for the display.

As mentioned above, the present invention has been described in detail with reference to preferred embodiments, but the present invention is not limited to the above embodiments, and various modifications may be made by those skilled in the art within the technical idea of the present invention. It is obvious.

For example, in the present embodiment, a device for printing a solution on a substrate using an electric charge concentration phenomenon has been described, but of course, it is also applicable to an apparatus for printing a solution on a substrate without using an electric charge concentration phenomenon.

In addition, although the printer body 40 is provided in this embodiment, the printer body 40 may not be provided.

In addition, in the present exemplary embodiment, a voltage in the form of a pulse is applied to the field forming electrode 20, but the object of the present invention can be achieved even if a voltage in the form of a pulse is not applied.

In addition, in the present embodiment, it is described that a pulse voltage of 100V to 100,000V is applied to the field forming electrode 20. However, even if the pulse voltage is out of the range, the efficiency is somewhat lowered, but the object of the present invention can be achieved. Can be.

 In addition, in the present embodiment, the pulse width of the pulse voltage is described as being 10 kV to 100 kV, but the object of the present invention can be achieved even if the pulse voltage is out of the range.

In the present embodiment, the pulse shape of the pulse voltage is described as being trapezoidal, but the pulse shape may be applied in various forms such as a sine wave.

In addition, in the present embodiment, the solution 10 is configured to charge positive charges and to induce negative charges on the substrate, but the negative charges are charged to the solution 10 and the substrate 30 faces the solution by the charged negative charges. The positive charge may be induced at a portion thereof, and the coulomb force is generated between the negative charge and the positive charge even in this configuration so that the solution 10 can be dropped onto the substrate 30 by the coulomb force.

In addition, in the present embodiment, the light sources 60 and 61 are arranged to be perpendicular to the length direction of the field forming electrode 20. However, the light sources 60 and 61 may be arranged at various positions as necessary. have.

In addition, in the present embodiment, the pump 66 is described as a syringe pump is preferable, but the pump 66 is not a syringe pump if it is possible to precisely pressurize or depressurize the solution contained in the receiving portion 22. It is also possible to achieve the object of the present invention.

In addition, in the present embodiment, the substrate 30 is an electrical non-conductor not grounded, and the lower side of the substrate 30 is configured to be an air layer so as not to affect the electric field caused by the open voltage application device 50. Even if the substrate 30 is grounded, the object of the present invention can be achieved, and the object of the present invention can be achieved even if the substrate 30 is an electrical conductor. As long as the structure does not affect the electric field caused by the open voltage application device 50, the object of the present invention can be achieved even without an air layer.

According to the present invention of the above configuration, by adjusting the solution containing the bioparticles or ink to have a predetermined predetermined volume has the effect of forming a spot of a predetermined size on the substrate. Therefore, a spot of more precise size can be formed compared with the prior art. As a result, the solution contained in the receiving portion is dropped onto the substrate in the same volume and attached to the substrate, thereby making it possible to manufacture a high-density biochip having the same size spot size.

Claims (26)

A needle-shaped solution droplet generating member which is arranged in a vertical direction and has a receiving part for receiving a solution, and a discharge hole connected to the receiving part and formed at a lower end of the receiving part so that the solution is discharged to the outside of the receiving part; A substrate disposed below the droplet generating member and having a target portion to which a solution discharged from a discharge port of the droplet generating member is attached to the substrate; A voltage applying device for applying a force to the droplets generated at the discharge port and causing the droplets to fall to the target portion of the substrate; Volume measuring means for measuring a volume of a droplet formed by protruding downwardly from the discharge port; And And solution control means for maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured by the volume measuring means. The solution control means is a device for printing a solution on a substrate comprising a pump for pressurizing or reducing the contained solution of the receiving portion. The method of claim 1, The volume measuring means, A light source for shining light rays on the solution droplets protruding downwardly from the discharge port; An image sensor detecting an image of the droplet generated by the light source; And And a computer processing device which receives the data sensed by the image sensor and calculates the volume of the solution droplets. 3. The method of claim 2, An apparatus for printing a solution on a substrate, characterized in that a diverging lens is disposed between the light source and the image sensor. 3. The method of claim 2, The light source is a laser light source, and an apparatus for printing a solution on a substrate, characterized in that a diverging lens for emitting light emitted from the laser light source is disposed between the laser light source and the droplet. The method of claim 3, The image sensor is a device for printing a solution on a substrate, characterized in that for detecting the one-dimensional image or two-dimensional image of the droplet. 3. The method of claim 2, And the light source is disposed perpendicular to the longitudinal direction of the droplet generating member. The method of claim 1, The volume measuring means, A light source is disposed above the accommodation portion, Apparatus for printing a solution on a substrate, characterized in that the image sensor is disposed below the substrate. delete The method of claim 1, And the pump is a syringe pump. It is made of a conductive material, is arranged long in the vertical direction, the needle-shaped having a receiving portion for receiving the solution, and the discharge port formed in the lower end of the receiving portion connected to the receiving portion and the solution is discharged to the outside of the receiving portion Field-forming electrodes; A substrate disposed below the field forming electrode, the substrate having a target portion to which a solution discharged from a discharge port of the field forming electrode is separated; The solution is electrically connected to the field forming electrode to charge the field forming electrode, and the solution is formed by a force generated between the charge charged in the field forming electrode and the charge induced in the substrate by the charge. An open voltage application device for falling to a target portion of the substrate; Volume measuring means for measuring a volume of a droplet formed by protruding downwardly from the discharge port; And And solution control means for maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured by the volume measuring means. The solution control means is a device for printing a solution on a substrate using an electric charge concentration phenomenon comprising a pump for pressurizing or reducing the contained solution of the receiving portion. The method of claim 10, The volume measuring means, A light source for shining light rays on the solution droplets protruding downwardly from the discharge port; An image sensor detecting a shadow image of the droplet generated by the light source; And And a computer processing device which receives the data sensed by the image sensor and calculates the volume of the solution droplets. The apparatus for printing a solution on a substrate using an electric charge concentration phenomenon comprising a. 12. The method of claim 11, An apparatus for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that the diverging lens is disposed between the light source and the image sensor. 12. The method of claim 11, The light source is a laser light source, and a solution is printed on a substrate using an electric charge concentration phenomenon, wherein a diverging lens is arranged between the laser light source and the droplet to emit light emitted from the laser light source. Device. The method of claim 12, The image sensor is a device for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that for detecting the one-dimensional image or two-dimensional image of the droplet. 12. The method of claim 11, The light source is an apparatus for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that disposed in the longitudinal direction of the field forming electrode. The method of claim 10, The volume measuring means, A light source is disposed above the accommodation portion, An apparatus for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that the image sensor is disposed below the substrate. delete The method of claim 10, The pump is a device for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that the syringe pump. The method of claim 10, The substrate is an electrical insulator that is not grounded, And the lower side of the substrate is an air layer so as not to affect the electric field by the open voltage application device. The method of claim 10, The solution comprises a bioparticle, wherein the bioparticle is selected from the group consisting of nucleic acids, proteins, oligopeptides, sugars, eukaryotic cells, viruses and bacteria. Printing device. The method of claim 10, The open voltage applying device is a device for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that to apply a pulse voltage having a pulse form so that an intermittent electric field is formed between the field-forming electrode and the substrate. . 22. The method of claim 21, A device for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that a pulse voltage of 100V to 100,000V is applied to the field forming electrode. 22. The method of claim 21, The pulse width of the pulse voltage is an apparatus for printing a solution on a substrate by using an electric charge concentration phenomenon, characterized in that 10㎲ to 100㎳. 22. The method of claim 21, The pulse type of the pulse voltage is an apparatus for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that the trapezoid. The method of claim 10, The solution is ink, The substrate is a device for printing a solution on the substrate by using the electric charge concentration phenomenon, characterized in that the printing paper or a printing substrate. In the method of printing a solution on a substrate using an electric charge concentration phenomenon, It is made of a conductive material, the needle-shaped field-forming electrode having a discharge port formed in the lower end of the receiving portion connected to the receiving portion and connected to the receiving portion and the solution is discharged to the outside of the receiving portion is extended in the vertical direction A field forming electrode arrangement step of placing; A substrate disposing step of disposing a substrate having a target portion to which a solution discharged from a discharge port of the field forming electrode is attached to the lower side of the field forming electrode; Arranging an open voltage applying device for arranging an open voltage applying device electrically connected to the field forming electrode; A solution supplying step of supplying the solution to a receiving portion of the field forming electrode; A voltage is applied to the field forming electrode from the open voltage applying device to charge the field forming electrode, and the solution is formed by a force generated between the charged charge and the charge induced in the substrate by the charge. Solution printing step of dropping to the target portion of the substrate; A volume measuring step of measuring a volume of a droplet formed by protruding downwardly from the discharge port; And And a solution adjusting step of maintaining the volume of the solution at a predetermined set volume based on the volume data of the solution measured in the volume measuring step. The solution control means in the solution control step is a method for printing a solution on a substrate using an electric charge concentration phenomenon, characterized in that it comprises a pump for pressurizing or reducing the contained solution of the receiving portion.

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