Patent Application
20090023609
This application claims the benefit of Korean Patent Application Nos. 10-2005-0119460, filed on Dec. 8, 2005, 10-2006-0056528, filed on Jun. 22, 2006, 10-2007-0120900, filed on Nov. 26, 2007, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.
1. Field of the Invention
The present invention relates to a programmable mask for fabricating a biomolecule array or polymer array, an apparatus for fabricating biomolecule array or polymer array including the programmable mask, a method of fabricating biomolecule array or polymer array using the programmable mask, and a photochemical synthesis apparatus.
2. Description of the Related Art
Research has been conducted on performing various kinds of experiments into one combined experiment using a biomolecule array or polymer array. Examples of a biomolecule array or polymer array include polypeptide, carbohydrate, or an array of nucleic acid (DNA, RNA). In order to conduct such an experiment, array having high density needs to be formed on a substrate with a reasonable price.
A conventional method of fabricating a biomolecule array or polymer array may be divided into spotting, electronic addressing and photolithography. Spotting is performed by having a micro robot selectively drop a biochemical substance on a desired spot while the micro robot three-dimensionally moves. Electronic addressing is performed by fixing a biomolecule to a specific electrode of a microelectrode array after controlling the electrode voltage. Photolithography is performed by selectively exposing a desired spot on a surface to light to change the surface, which then causes a reaction at a specific location due to bonding between the surface and a biomolecule at the specific location.
In more detail, the spotting method is divided into contact printing and non-contact printing in which a solution is stamped on a paper and a solution is dropped on a paper, respectively. In contact printing, loading, printing, and washing are sequentially performed by an XYZ robot. Non-contact printing can be divided into dispensing and ink-jet printing. Dispensing involves applying a solution in a dropwise fashion, like when a micropipette is used. Ink jet printing involves applying minute pressure to a reservoir which causes a solution to be ejected.
Electronic addressing involves fixing a biomolecule to a plate using a voltage control function of the microelectrode array. Electronic addressing can be divided into a method of generating a physicochemical bond by moving a biomolecule having an electric charge to the surface of an electrode and a method of fixing a biomolecule in a thin film when the thin film is formed by electrochemical deposition.
Photolithography used in a semiconductor production process can be used to manufacture an array having high density and enables parallel synthesis. However, a number of photo masks is required, thereby increasing cost and consuming time. Therefore, a programmable mask which can control light paths through a plurality of pixels without using a photo mask is being developed and is disclosed in U.S. Pat. No. 6,271,957. The programmable mask includes a method of regulating reflection of light and a method of regulating penetration of light. For example, a micromirror array or a liquid crystal display (LCD) can be used.
The method of fabricating a biomolecule array has two problems: fabrication of a high density pattern is difficult due to diffraction of incident light, and more time is needed for forming a biomolecule such as DNA synthesis, since light intensity is decreased due to an insufficient amount of light penetration on a polarizing plate disposed at both ends of a panel in a LCD. The reasons of raising such problems are described below.
Although a mosaic patterned oligomer array can be manufactured with an increase in the density of a DNA pattern, the amount of polarized light transmitted through a UV polarizing plate is small, and thus, UV exposure time which is 10 times greater is required compared to the case where photo masks for manufacturing the semiconductor are used.
The present invention provides a programmable mask for fabricating biomolecule or polymer array having high density in very short time.
The present invention also provides an apparatus for fabricating biomolecule or polymer array having high density in very short time.
The present invention also provides a method of fabricating biomolecule or polymer array having high density in very short time.
The present invention also provides a photochemical synthesis apparatus capable of precisely defining location of regions in which photochemical synthesis occurs.
The present invention also provides a photochemical synthesis apparatus capable of easily changing location of regions in which photochemical synthesis occurs.
The present invention also provides a photochemical synthesis apparatus capable of inexpensively determining location of regions in which photochemical synthesis occurs.
According to an aspect of the present invention, there is provided programmable mask for fabricating a biomolecule array or polymer array, the mask including: a first substrate including a black matrix having openings for incident UV and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin film transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate to polarize UV light; a second polarizing plate laminated on one side of the second substrate to polarize UV light; and a lens array layer laminated on one side of the second polarizing plate including lenses which correspond to the pixel regions.
The programmable mask may further include a driving circuit for driving the thin film transistors on the second substrate, the driving circuit being disposed outside the pixel regions.
The lens may be a hemispherical lens or a gradient index lens. The polarizing plate may have high transmittance with respect to UV light having wavelength of 320-400 nm.
The biomolecule may be nucleic acid or protein.
The nucleic acid may be selected from the group consisting of DNA, RNA, PNA, LNA, and a hybrid thereof.
The protein may be selected from the group consisting of enzyme, substrate, antigen, antibody, ligand, aptamer, and receptor.
According to another aspect of the present invention, there is provided an apparatus for fabricating a biomolecule array or polymer array including: a UV light generator including a UV light source and a lens unit through which UV light irradiated from the UV light source passes; a programmable mask for fabricating a biomolecule or polymer; wherein the programmable mask includes: a first substrate disposed so as to be spaced apart from the UV light generator, the first substrate including a black matrix having openings for incident UV light and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate to polarize UV light; a second polarizing plate laminated on one side of the second substrate to polarize UV light; and a lens array layer laminated on one side of the second polarizing plate including lenses which correspond to the pixel regions; and an array forming chamber forming a biomolecule array or polymer array, wherein the array forming chamber is laminated on the programmable mask and includes a sample plate on which the biomolecule or polymer array is formed, and a washing solution and a biomolecule or polymer flow in and out of the array forming layer.
The UV light source may be a LED two dimensional array or a laser diode two dimensional array.
The lens unit of the UV light generator may include a homogenizer lens unit to make UV light generated by the UV light source uniform, a field lens to concentrate UV light generated by the homogenizer lens unit, and a convex lens to make UV light generated by the field lens parallel.
The focal point of the lens of the programmable mask may be formed on the sample plate where a biomolecule array or polymer array is formed.
The lens of the programmable mask may be a hemispherical lens or a gradient index lens.
According to another aspect of the present invention, there is provided a programmable mask for fabricating a biomolecule array or polymer array including: a first substrate including a black matrix having openings and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin film transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate to polarize UV light; and a second polarizing plate laminated on one side of the second substrate including a polarizing layer and a biomolecule or polymer fixed layer.
As another embodiment of the present invention, the second polarizing plate may include the polarizing layer, protecting layers laminated on both sides of the polarizing layer, and a biomolecule or polymer fixed layer having a hydrophilic surface on which a biomolecule or polymer can be fixed.
The second polarizing plate may be attached to and detached from the second substrate.
The programmable mask may further include a driving circuit for driving the thin film transistors on the second substrate, the driving circuit being disposed outside the pixel regions.
The polarizing plate may have high transmittance with respect to UV having wavelength of 320-400 nm.
The liquid crystal, as a liquid crystal in which dyes are included in a nematic liquid crystal, may be a guest-host type liquid crystal enabling to intercept or transmit light, since a vibration direction of linear polarized light and light absorption axis of the dyes are same or cross at right angles.
According to another aspect of the present invention, there is provided an apparatus for fabricating a biomolecule array or polymer array including: a UV light generator including a UV light source and a lens unit through which UV light irradiated from the UV light source passes; a programmable mask for fabricating a biomolecule or polymer; wherein the programmable mask includes: a first substrate disposed so as to be spaced apart from the UV light generator, the first substrate including a black matrix having openings and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate to polarize UV light; and a second polarizing plate laminated on one side of the second substrate to polarize UV light including a polarizing layer and a biomolecule or polymer fixed layer; and an array forming chamber forming a biomolecule array or polymer array, wherein the array forming chamber is disposed on the lower part of the second polarizing plate, and a washing solution and a biomolecule or polymer flow in and out of the array forming layer.
The UV light source may be a LED two dimensional array or a laser diode two dimensional array.
The lens unit of the UV light generator may include a homogenizer lens unit to make UV light generated from the UV light source uniform, a field lens to concentrate UV light generated from the homogenizer lens unit, and a convex lens to make UV light generated by the field lens parallel.
The second polarizing plate may include the polarizing layer, protecting layers laminated on both sides of the polarizing layer, and the biomolecule or polymer fixed layer having a hydrophilic surface on which a biomolecule or polymer can be fixed.
The second polarizing plate may be attached to and detached from the second substrate.
According to another aspect of the present invention, there is provided an apparatus for fabricating a biomolecule array or polymer array including: a UV light generator including a UV light source and a lens unit, wherein UV light irradiated from the UV light source is passed through the lens unit; a programmable mask; wherein the programmable mask includes: a first substrate disposed so as to be spaced apart from the UV light generator to have a predetermined angle with a propagation path of UV light generated by the UV light generator, the first substrate including a black matrix having openings and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals, second pixel electrodes connected to drain electrodes of the thin transistors, and reflection layers for reflecting incident UV; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; and an array forming chamber forming a biomolecule array or polymer array, wherein the array forming chamber is spaced apart from the programmable mask to have a right angle to the UV light path reflected from the programmable mask and includes a sample plate on which the biomolecule or polymer array is formed, and a washing solution and a biomolecule or polymer flow in and out of the array forming layer.
The UV light source may be a LED two dimensional array or a laser diode two dimensional array
The lens unit of the UV light generator may include a homogenizer lens unit to make UV light generated from the UV light source uniform, a field lens to concentrate UV light generated from the homogenizer lens unit, and a convex lens to make UV light generated from the field lens parallel.
According to another aspect of the present invention, there is provided a method of fabricating a biomolecule array or polymer array using a programmable mask for fabricating a biomolecule array or polymer array, wherein the programmable mask includes: a first substrate including a black matrix having openings and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin film transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate; a second polarizing plate laminated on one side of the second substrate; and a lens array layer laminated on one side of the second polarizing plate including lenses which correspond to the pixel regions, the method including: irradiating UV light to selective regions of a sample plate on which molecules having a protecting group are fixed through the programmable mask; and flowing a solution containing biomolecule or polymer monomer, required to fix to the molecule.
According to another aspect of the present invention, there is provided a method of fabricating a biomolecule array or polymer array using a programmable mask for fabricating a biomolecule array or polymer array, wherein the programmable mask includes: a first substrate including a black matrix having openings and first pixel electrodes; a second substrate including thin film transistors for switching pixel regions which correspond to the openings according to applied electric signals and second pixel electrodes connected to drain electrodes of the thin film transistors; a liquid crystal layer interposed between the first substrate and the second substrate, the liquid crystal layer including liquid crystal whose arrangement can be changed according to electric signals of the thin film transistors so as to selectively transmit light; a first polarizing plate laminated on one side of the first substrate; and a second polarizing plate laminated on one side of the second substrate including a polarizing layer and a biomolecule or polymer fixed layer, the method including: irradiating UV light to selective regions of a sample plate on which molecules having a protecting group are fixed through the programmable mask; and flowing a solution containing biomolecule or polymer monomer, required to fix to the molecule.
According to another aspect of the present invention, there is provided a photochemical synthesis apparatus for selectively forming source materials in a predetermined region on a substrate, the apparatus including: a reaction chamber onto which the substrate is loaded and into which reaction molecules forming the source materials are supplied; a light source providing reaction light, the light source being disposed above the substrate; and a transmission region controller variably controlling regions through which the reaction light can be transmitted to the substrate, the transmission region controller being disposed between the light source and the substrate, wherein the reaction light comprises laser light having a high degree of coherence.
The reaction light has a wavelength which induces the source materials to be attached to the substrate. In addition, the source materials may include at least one of DNA monomers for analyzing gene expression and single nucleotide polymorphism, an activator solution, amino acids and proteins for protein synthesis, monomers and polymers for polymer synthesis, and a cleaning solution. Here the source materials may include a protecting molecule capable of being photo-deprotected by the reaction light.
The transmission region controller may include transmission regions that are two dimensionally arranged, the transmittance of the transmission regions being controlled in response to an electrical signal. For example, the transmission region controller may include a liquid crystal display (LCD) using a voltage-transmittance characteristic of a liquid crystal layer, the LCD including: pixels that are two-dimensionally arranged; a pixel controller generating an operating voltage for controlling transmittance of the pixels; and wirings connecting to the pixels and transmitting the operating voltage to the pixels.
The source materials may include at least one of a plurality of DNA monomers, the reaction light comprises laser light having a wavelength of a UV band and a high degree of coherence. Here, the operating voltage may be selected to prevent the LCD being damaged by the laser light having a wavelength of a UV band.
The transmission region controller may be configured to have a narrow viewing angle (for example, approximately 0-45 degrees) and may be approximately 0-10 degrees.
The photochemical synthesis apparatus may further include a reaction light controller for controlling at least one of progressing direction, intensity, and incident angle to the substrate of the reaction light, the reaction light controller being disposed between the light source and the substrate. Here, the reaction light controller may be configured for the reaction light to form parallel light which is substantially vertically incident to the upper surface of the substrate.
According to another aspect of the present invention, there is provided a photochemical synthesis apparatus for selectively forming source materials in a predetermined region on a substrate, the apparatus including: at least one light source generating reaction light; a plurality of reaction chambers onto which a plurality of substrates are respectively loaded; a reaction light controller guiding the reaction light to the substrates; and a transmission region controller variably controlling regions through which the reaction light can be transmitted to the substrates, the transmission region controller being disposed between the reaction light controller and the substrates, wherein the reaction light controller comprises a plurality of optical splitters splitting the reaction light so as to be provided to the plurality of substrates.
The reaction light controller may include a plurality of half mirrors which split the reaction light into transmission light and reflection light, each progressing in a direction parallel to and perpendicular to the incident light, the half mirrors being configured for the transmission light or reflection light transmitted by the light source or another of the half mirrors to be transmitted to the substrate or another of the half mirrors.
The reaction light controller may be configured for intensity of the reaction light incident to the substrates to be substantially the same. For example, the optical splitters may be disposed to correspond to the substrates, respectively, and the reaction light controller further comprises one or more attenuators disposed between at least one of the substrates and the corresponding optical splitters. Here, the attenuators disposed between the substrate and corresponding optical splitter may be configured to have reduced attenuation if the number of optical splitters arranged on the progressing path of the reaction light incident to the substrates is increased.
The reaction light controller may be configured to form a path of a first reaction light incident to the substrates in a first order and a path of a second light reaction incident to the substrates in a second order opposite to the first order, between the reaction light and the substrates.
The reaction light may include laser light having a wavelength which induces the source materials to be attached to the substrates, and a high degree of coherence. In addition, the source materials may include at least one of DNA monomers for analyzing gene expression and single nucleotide polymorphism, an activator solution, amino acids and proteins for protein synthesis, monomers and polymers for polymer synthesis, and a cleaning solution. The source materials may include a protecting molecule capable of being photo-deprotected by the reaction light.
The transmission region controller may include transmission regions that are two dimensionally arranged, the transmittance of the transmission regions being controlled in response to an electrical signal. For example, the transmission region controller may include a liquid crystal display (LCD) using a voltage-transmittance characteristic of a liquid crystal layer, the LCD comprising: pixels that are two-dimensionally arranged; and a pixel controller generating an operating voltage for controlling transmittance of the pixels, the pixel controller controlling transmittance of the pixels according to location of the pixels and the types of the source materials applied to the reaction chambers, in order for the source materials to be formed as different stacking structures on the substrates, respectively.
The source materials may include at least one of a plurality of DNA monomers, the reaction light comprises laser light having a wavelength of a UV band and a high degree of coherence, and the operating voltage is selected to prevent the LCD being damaged by the laser light having a wavelength of a UV band. For example, the operating voltage may be selected for the liquid crystal layer to be operated in a complete transmission mode and a complete blocking mode.
Meanwhile, the reaction light controller may be configured for the reaction light to form parallel light which is substantially vertically incident to the upper surface of the substrate.
The above and other features and advantages of the present invention will become more apparent by describing in detail exemplary embodiments thereof with reference to the attached drawings in which:
Hereinafter, the present invention will be described more fully with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown.
In order to analyze the stability of liquid crystal and an alignment film of a LCD with respect to UV, a UV polarizing plate of the LCD is separated and removed, and UV light having wavelength of 350 nm and an intensity of 160 mW/cm2 used in a DNA synthesis is irradiated onto the LCD. Then, the polarizing plate for UV is attached back to the LCD and the transmittance with respect to voltage and contrast change with respect to UV exposure time are analyzed using a UV-visible spectrophotometer.
Referring to
In synthesis of DNA oligomer, UV light is transmitted to a LCD in a complete transmission mode or completely blocked in a complete blocking mode for UV photo deprotection of a deprotecting group such as NPPOC[2-(2-nitrophenyle)-ethoxycarbony] and molecule, MeNPOC[((alpha-methyl-2-nitropipheronyl)-oxy)carbonyl], after optical pumping used in synthesis of photolithgraphic DNA which is attached to a side chain 5′ of a DNA monomer.
When LCDs are used for display purposes, color is embodied by slightly changing the amount of light to specific pixels. However, when a LCD is used as a mask, UV light is completely transmitted to the LCD or completely intercepted for photo deprotection of UV.
In a DNA chip, an oligonucleotide is generally formed by coupling 25 DNA monomers together. Spots disposed on a DNA chip glass substrate, which correspond to openings in the liquid crystal, couple with DNA molecules according to predetermined DNA sequences. The spots disposed on the DNA chip, which correspond to the respective pixels, have different DNA sequences. Nucleotide formed of DNA includes adenine (A), thymin (T), cytosine (C), and guanine (G). First, as an example of synthesis, adenine (A) is formed on a region of the DNA chip which corresponds to a specific pixel. Then, when thymin (T) is synthesized in a region corresponding to another pixel, the region where adenine (A) is synthesized may be prevented from being synthesized with thymin (T). DNA bases which are attached to the DNA chip have a protecting group attached thereto, so if other bases approach the DNA bases, coupling does not occur before UV is irradiated.
Adenine (A) of the specific pixel described above also has a protecting group attached thereto, so if other bases approach the DNA bases, coupling does not occur before UV is irradiated. However, in order to synthesize thymin (T) with another pixel, during UV light irradiation, no UV light should reach the protecting group in adenine (A) attached to the specific pixel. That is, a specific pixel of the LCD according to the present invention should minimize UV leakage in a complete blocking mode. Spots on the DNA chip, which correspond to the respective pixels, have specific regions, wherein oligonucleotides exist in the region.
If some UV light is leaked from a specific pixel of the liquid crystal, thymin (T) is coupled to a specific adenine (A) on a region of the DNA chip which corresponds to the specific pixel, while some of the oligonucleotides become oligonucleotides having different sequences, and thus, the yield of the synthesis is decreased. Since incident UV light is in the form of a UV beam that is bigger than the area of the LCD, a liquid crystal cell is needed to completely block UV light. When UV is irradiated on an alignment layer and on liquid crystal, and thus, a gray scale is destroyed, damage due to UV occurs when the LCD is used as a display such as a TV or monitor. However, as illustrated in
Referring to
Here, the programmable mask is an apparatus to control transmission, reflection, and interception of incident light in a pixel unit.
The programmable mask includes a first substrate 410 including a black matrix 430 having openings and first pixel electrodes (not illustrated); a second substrate 400 including thin film transistors (not illustrated) for switching pixel regions which correspond to the openings in response to applied electric signals and second pixel electrodes (not illustrated) connected to drain electrodes of the thin film transistors; a liquid crystal layer 420 interposed between the first substrate 410 and the second substrate 400 and including liquid crystal to selectively transmit light after arrangement of the liquid crystal layer 420 is changed according to electric signals of the thin film transistors; a first polarizing plate 445 laminated on one side of the first substrate 410; a second polarizing plate 440 laminated on one side of the second substrate 400; and a hemispherical lens array layer 450 laminated on one side of the second polarizing plate 440 and including hemispherical lenses which correspond to the pixel regions.
The programmable mask may further include a driving circuit for driving the thin film transistors on the second substrate 440 in the outer pixel region, but a driving circuit is not illustrated.
In the present invention, the polarizing substrates 440 and 445 may have high transmittance with respect to UV having a wavelength of 320-400 nm. The liquid crystal, which is a liquid crystal in which dyes are included in a nematic liquid crystal, is a guest-host type liquid crystal enabling light to be to intercepted or transmitted, since a vibration direction of linear polarized light and the light absorption axis of the dyes are the same or cross at right angles.
The biomolecule of the present invention may be a nucleic acid or a protein. The nucleic acid can be selected from the group consisting of DNA, RNA, PNA, LNA, and a hybrid thereof. The protein can be selected from the group consisting of enzyme, substrate, antigens, antibodies, ligands, aptamers, and receptors.
Biomolecules or polymers, for example, a DNA monomer having a side chain molecule that can be desorbed by UV light, such as 5′-NPPOC (or MeNPOC)-dT, 5′-NPPOC (or MeNPOC)-dA, 5′-NPPOC (or MeNPOC)-dG, and 5′-NPPOC (or MeNPOC)-dC, and a washing solution 465 can flow in and out of the array forming chamber 460.
The hemispherical lens array layer 450 can be used to focus the UV energy so as to make it high enough for desorption of molecules such as NPPOC and MeNPOC, wherein the NPPOC and MeNPOC can be attached to a side chain of a DNA nucleotide (dA,dT,dG,dC) and can be desorbed by UV light.
The programmable mask includes the hemispherical lens array layer 450 on the side where two glass substrates of a backlit LCD or the quartz substrates 400 and 410 through which UV is transmitted to be out and thus, the UV out through the each pixel is collected. Therefore, UV irradiation time is reduced and mixing with other adjacent patterns can be prevented.
The hemispherical lens can be formed using a hemispherical mold when a glass substrate is manufactured on the glass substrate of the backlit LCD. Instead of directly forming the hemispherical lens on the glass substrate of the backlit LCD, the hemispherical lens array may be formed on another glass substrate which is then attached to the glass substrate of the backlit LCD so that the hemispheres correspond one-to-one with the LCD pixels. The hemispherical lens optically collects incident light and improves the intensity of UV. In addition, the focal point of the hemispherical lens may be formed on the lower part of the DNA oligomer chip substrate disposed on the DNA oligomer synthesis chamber.
Unlike in
The focal distance 530 of the gradient index lens may be chosen so that the focal point is formed around a lower part of a DNA oligomer chip substrate 520 disposed on a DNA synthesis chamber. Accordingly, the intensity of UV light is expected to increase by more than 5 times around the focal point 530 of the gradient index lens due to the collecting of UV light and thus, synthesis time can be reduced to ⅕ or less of the normal time. Also, a spot surface 540 of oligomer pattern can be significantly reduced and density of oligomer pattern can be improved.
A method of forming gradient index lens (Grin lens) array includes making a hole in an opaque substrate such as a silicon substrate so as to correspond one-to-one with the LCD pixels, inserting grin lenses into each hole disposed on the substrate, and attaching the substrate to a lower part of a glass substrate of the LCD. The grin lens of the present invention has an object of improving intensity of UV by optically collecting incident light. Therefore, the focal point of the grin lens may be selected to be formed on the lower surface of the DNA oligomer chip substrate disposed on the DNA oligomer synthesis chamber.
Referring to
Referring to
The second polarizing plate 700 disposed on the lower substrate of the LCD is formed to reduce optical diffraction by removing the distance between chip glass substrates in the oligomer synthesis chamber. The substrates are glass or quartz substrates formed of LCDs. The second polarizing plate 700 attached to the outer surface of the lower substrate is used not only for optical purposes to get polarized light but also as a DNA oligomer chip substrate.
In general, the glass substrate on the DNA oligomer synthesis chamber, that is, the DNA oligomer chip substrate, is formed of a glass substrate having a thickness of 600-1000 um. UV light that passes through a lower polarizing plate of a backlit LCD passes through the glass substrate and a predetermined amount of UV light is diffracted. Disadvantages regarding this are fully described in the description of
The biomolecule or polymer fixed layer 820 may be a thin film to which a hydroxyl group (—OH) or an amine group (NH3) can be attached, for example, a silicon oxide layer. When the first DNA monomer flows into the synthesis chamber in a synthesis process, 3′ part of a monomer is combined with the hydroxyl group (—OH) or the amine group (NH3) attached to the fixed layer 820. Then, as the synthesis process progresses, a DNA oligomer 830 is formed.
The polarizing substrate on which the DNA oligomer is synthesized can be separated from the lower glass substrate of the backlit LCD to perform DNA hybridization after the DNA oligomer is synthesized.
Referring to
The liquid crystal layer 960 is connected to a voltage, and thus, incident light is transmitted and reflected through the liquid crystal layer 960 and reflected light 980 is emitted. However, voltage is removed in another liquid crystal layer 970 and incident light is intercepted, and thus, reflected light cannot be emitted (990).
Referring to
UV incident light 1070 is incident to a normal of an upper glass substrate 1010 of the reflective LCD panel with a predetermined incident angle 1090. A reflective angle is the same as the incident angle and light is reflected on the opposite side of the normal at the reflective angle. Reflected light 1080 synthesizes an oligomer nucleotide on the lower part of the DNA chip glass substrate of a DNA synthesis chamber.
The propagation direction of the reflected light 1080 reflected from the liquid crystal using the reflective LCD is set to cross at right angles to the upper DNA chip glass substrate of the DNA synthesis chamber.
In general, conventional UV irradiators formed of a mercury lamp and optical lens for irradiating UV incident light to a LCD panel are large and have a volume of 1 to 3 meters. Therefore, a UV light generator having a relatively small size to get uniform UV beams is proposed in the present invention.
Referring to
The UV light source 1110 may be a LED two dimensional array or a laser diode two dimensional array.
The lens unit of the UV light generator 1110 may include a homogenizer lens unit 1120 to make UV generated from the UV light source 1110 uniform, a field lens 1125 to concentrate UV generated from the homogenizer lens unit 1120, and a convex lens 1130 to make UV generated from the field lens 1125 parallel.
As illustrated in the drawings described above, the present invention also provides a method of fabricating a biomolecule array or polymer array using the programmable mask or the apparatus for fabricating an array. The method includes irradiating UV light to selected regions of a sample plate on which molecules having a protecting group are fixed through the programmable mask and flowing a solution containing a biomolecule or a polymer monomer, required to fix to the molecule.
As described above, a biomolecule array or polymer array on which biomolecules or polymers are fixed with higher density than that of a conventional biomolecule array or polymer array can be achieved according to the present invention. Also, the time required for manufacturing the biomolecule or polymer array can be reduced.
Referring to
The substrate 2120 is loaded onto the reaction chamber 2110 and source materials 2115 for photochemical synthesis are supplied to the reaction chamber 2110. In order to supply the source materials 2115 to the reaction chamber 2110, pipes (not shown) for inflow and outflow of the source materials 2115 are connected to the reaction chamber 2110 and the pipes may be connected to a container (not shown) storing the source materials 2115 and a collecting container to which the source materials 2115 are delivered, or other reaction chamber.
The photochemical synthesis apparatus 2100 according to the current embodiment of the present invention may be used to manufacture chips for analyzing gene expression or single nucleotide polymorphism. In this case, the source materials 2115 may include at least one of DNA monomers, an activator solution, and a cleaning solution. Here, for selective synthesis by light, NPPOC[2-(2-nitrophenyle)-ethoxycarbony], MeN POC[((alpha-methyl-2-nitropipheronyl)-oxy)carbonyl] protecting molecule having a photo-deprotection characteristic may be attached to side branches of DNA monomers. When the protecting molecule is not attached to DNA monomers by light generated by the light source 2150, the corresponding DNA monomer is not coupled with other DNA monomers.
In addition, the photochemical synthesis apparatus 2100 according to the current embodiment of the present invention may be used to selectively synthesize proteins or polymers. In this case, the source materials 2115 may include amino acids and proteins for protein synthesis or monomers and polymers for polymer synthesis. Meanwhile, the source materials 2115 are illustrated for schematically explaining the technical field to which the present invention can be applied. However, the technical idea of the present invention is not limited to the above-described source materials and can be applied to various other technical fields based on photochemical synthesis.
The light source 2150 generates light having a predetermined wavelength and the light (hereinafter, referred to as a reaction light 2155) provides reaction energy for a coupling reaction in which the source materials 2115 are attached to the lower surface of the substrate 2120. Accordingly, the light source 2150 is formed to generate the reaction light 2155 having a frequency that is greater than a predetermined critical frequency or intensity that is greater than a predetermined critical intensity. In addition to this, in order to precisely define regions where the coupling reaction of the source materials 2115 occurs, the light source 2150 is formed for the reaction light 2155 to have a high degree of coherence. For example, the reaction light 2155 may be laser light having a wavelength of a UV band (more specifically, a wavelength of 310 nm to 370 nm). However, the wavelength and intensity of the reaction light 2155 may be determined according to the types of the source materials 2115 and are not limited thereto. Meanwhile, the photochemical synthesis apparatus 2100 according to the current embodiment of the present invention is configured for the reaction light 2155 to cover an area the same as or greater than that of the transmission region controller 2130 and to be incident to the transmission region controller 2130.
The transmission region controller 2130 determines the region through which the reaction light 2155 can be transmitted. That is, the extent of the region on the substrate 2120 to which the reaction light 2155 can reach is determined by the transmission region controller 2130. As described above, in photochemical synthesis, the coupling reaction between the source materials 2115 and the substrate 2120 occurs according to whether the reaction light 2155 is incident and thus the transmission region controller 2130 which determines the transmission region of the reaction light 2155 determines location of the region where photochemical synthesis occurs. In other words, the planar location of a material layer 2200 grown through photochemical synthesis is determined by the transmission region controller 2130 and a vertical configuration thereof is determined by changing the supplied source materials 2115.
Meanwhile, according to the current embodiment of the present invention, the transmission region controller 2130 is configured for the transmission region to be changed according to needs of users. For example, the transmission region controller 2130 may include transmission regions that are two-dimensionally arranged, wherein the transmittance of each transmission region is electrically controlled. According to the current embodiment, the transmission region controller 2130 may be a liquid crystal display (LCD) having a liquid crystal layer in which transmittance thereof is controlled by a voltage applied thereto.
A conventional photo-mask also includes patterned chrome patterns so as to determine a region through which the reaction light 2155 is transmitted. However, the transmission region cannot be freely changed by the photo-mask. Thus, a conventional photo-mask is required to be changed according to the types of the supplied source materials, in order to form synthesized materials layers each having a different molecular structure. Unlike this, the transmission region controller 2130 according to the current embodiment of the present invention can variably control the transmission regions according to needs of users, as described above, so that the regions where photochemical synthesis occurs can be controlled without changing the photo-mask.
Referring to
Protecting molecules of a DNA monomer are attached to regions 201, 202, and 204 disposed under pixels PX (ON) having high transmittance and are not attached to a region 203 disposed under pixels PX (OFF) through which transmission of a reaction light 2155 is blocked. Accordingly, DNA monomers included in source materials 2115, as illustrated, can be selectively grown only in the regions 201, 202, and 204 disposed under the pixels PX (ON) having high transmittance.
The LCD 140 includes polarizers 132 and 138 and a liquid crystal layer 134. The LCD 140 may also include operating devices (not shown) arranged in each pixel PX for controlling transmittance of the liquid crystal layer 134, and wirings (not shown) connecting the operating devices. In addition to this, alignment layers (not shown) may be further disposed on the upper part and lower part of the liquid crystal layer 134 for controlling arrangement of liquid crystal, and shielding patterns 136 defining the pixels PX may be further disposed on the upper part or lower part of the liquid crystal layer 134.
According to the current embodiment of the present invention, the LCD 140 is configured to prevent the liquid crystal layer 134 and the polarizers 132 and 138 from being thermalized by the reaction light 2155. For example, the LCD 140 may further include a temperature controller (not shown) for reducing thermal stress occurring due to the reaction light 2155. The temperature controller may be a cooling device using the Peltier effect.
According to another embodiment of the present invention, the pixel controller may be configured to generate an operating voltage capable of preventing the liquid crystal layer 134 from being thermalized by the reaction light 2155. Based on an experiment conducted by the inventors of the present invention, when an operating voltage, which realizes a complete blocking mode and a complete transmission mode, is applied to the liquid crystal layer 134, transmittance of the reaction light 2155 can be controlled without actual thermalization of the liquid crystal layer 134.
More specifically, in this experiment, UV light with a wavelength of 350 nm was incident to a plurality of LCDs, from which polarizers are removed, at radiant flux per unit area of 160 mW/cm2, and the polarizers were attached again to the LCDs to which the UV light was incident. Then, a voltage-transmittance characteristic of the LCDs to which the UV light was incident was measured using an Ultraviolet-Visible spectrophotometer. The time taken for irradiating UV to each LCD was two, eight, and eighty minutes, respectively.
According to the results of the experiment, transmittance of the LCDs in a voltage range of approximately 2.5-3 V (hereinafter, referred to as a complete blocking mode) is approximately 0 and is not related to the time for which UV light is incident and a voltage change within the range. In addition, in a voltage range of approximately 0-1.5 V (hereinafter, referred to as a complete transmission mode), transmittance is reduced from approximately 0.5 to 0.35. However, the transmittance is restored to approximately 0.42 as time passes and is not related to a voltage change within the range. Unlike this, in a voltage range of 1.5-2.5 V (hereinafter, referred to as a grey scale mode), the transmittance is rapidly changed according to a change in applied voltage.
For LCDs having the purpose of realizing various colors, stability of the grey scale mode must be satisfied as an important technical requirement. However, since photochemical synthesis reaction is determined according to whether the reaction light 2155 is incident to the substrate 2120, it is sufficient that the LCD 140 has a voltage condition for completely blocking the reaction light 2155 and for the reaction light 2155 to be stably transmitted through the LCD 140. From this point of view, an important technical requirement for photochemical synthesis is stability of the complete blocking mode, instead of stability of the grey scale mode. As a result of the experiment conducted by the inventors, the LCD according to the present invention satisfies such technical requirement.
Meanwhile, transmittance in the grey scale mode varies according to the applied voltage and the time for which UV light is incident, as described above, and thus intensity of light that is incident to the substrate 2120 cannot be stably controlled. However, in the complete transmission mode, transmittance is not affected by the applied voltage and the time for which UV light is incident, as described above, and thus intensity of the reaction light can be stably controlled. Accordingly, the LCD 140 according to the current embodiment of the present invention can be configured to operate in an operating voltage range which realizes the complete blocking mode and complete transmission mode. Here, the range of operating voltage for the complete blocking mode and complete transmission mode varies according to types and structure of the liquid crystal materials, and the structure of the used LCD.
Moreover, in the technical field of LCDs, various technologies for securing a wide viewing angle have been suggested. However, the wide viewing angle makes spatial confinement of the transmission region difficult. Thus, the LCD according to the present invention is configured to have a narrow viewing angle (for example, approximately 0 to 45 degrees). More preferably, the viewing angle may be in the range of approximately 0 to 10 degrees. From this point of view, the LCD according to the present invention is the same as a conventional LCD in terms of the operating method thereof and is different from a conventional LCD in terms of the configuration thereof.
Thus, the liquid crystal layer 134 and the types and structure of the alignment layers are configured to realize a narrow viewing angle.
Referring to
In order to improve reliability of an analyzing chip, material layers 2200 each having a different stacking structure are required to be partially formed in each of analyzing regions. Accordingly, the reaction light controller 2160 may be configured for the reaction light 2155 generated in the light source 2150 to be substantially vertically incident to the upper surface of the substrate 2120. When the reaction light 2155 is vertically incident to the substrate 2120, the area A2 of the region in which the material layer 2200 is formed is substantially equal to the area A1 of the corresponding pixel PX, as illustrated in
Meanwhile, when a gap between the analyzing regions is sufficiently large, the reaction light 2155 may not be required to have a specific incident angle. In addition to this, according to another embodiment of the present invention, the area of the region where the material layer 2200 is formed may be less than the area of the corresponding pixel. Thus, the reaction light controller 2160 may be configured to have a cross section that gradually narrows in the direction of the reaction light 2155. The technical requirement relating to the incident angle of the reaction light 2155 may be satisfied by controlling the configuration and arrangement of optical components forming the reaction light controller 2160.
Referring to
Each of the reaction light controllers 2160 of
According to the current embodiments, the optical splitters 2310a, 2310b, 2310c, . . . , and 2310d may be a half mirror which splits incident light IL respectively into reflection light RL and transmission light TL. The reflection light RL or transmission light TL which passes through a predetermined optical splitter (for example, the optical splitter 2310a) is incident to another optical splitter (for example, the optical splitter 2310b) and is split again into the reflection light RL and transmission light TL. At least one of the reflection light RL and transmission light TL is incident to one of the corresponding transmission region controllers 2130a, 2130b, 2130c, . . . , and 2130d. In
According to such configuration, one reaction light 2155 is used to simultaneously perform photochemical synthesis in the reaction chambers 2110a, 2110b, 2110c, . . . , and 2110d so that productivity of the product can be improved. Moreover, as illustrated in
Meanwhile, according to the current embodiments of the present invention, the reaction light controller 2160 may be configured to uniformly form an optical characteristic of light incident to the transmission region controllers 2130a, 2130b, 2130c, . . . , and 2130d.
For example, as illustrated in
According to another embodiment of the present invention, as illustrated in
According to another embodiment of the present invention, as illustrated in
Here, as described with reference to
Such optical components, as described above with reference to
More specifically,
In
Moreover, the photochemical synthesis apparatus according to the present invention uses laser light having a high degree of coherence as a light source. Such a high degree of coherence enables the transmission region defined by the transmission region controller to be transcribed onto the substrate without substantial change in the area thereof. Thus, a change in the cross section of the reaction light which may occur while the light is transmitted through the transmission region controller can be reduced. In addition to this, according to the present invention, the transmission region controller has a narrow viewing angle so as to reduce a change in the cross section of the reaction light.
According to the present invention, the reaction light controller, which controls the reaction light, includes optical splitters. The photochemical synthesis can be simultaneously performed in a plurality of reaction chambers using the optical splitters so that the photochemical synthesis apparatus according to the present invention can have high productivity. Here, the transmission region controller can separately control the transmission region of each of a plurality of substrates loaded onto a corresponding one of the reaction chambers and thus a different product can be manufactured in each reaction chamber.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2005-0119460 | Dec 2005 | KR | national |
| 10-2006-0056528 | Jun 2006 | KR | national |
| 10-2007-0120900 | Nov 2007 | KR | national |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11634408 | Dec 2006 | US |
| Child | 12174773 | US |
