Protein crystal growth monitoring device

Abstract

In one embodiment, the protein crystal growth monitoring device may comprise: a crystal growth module for growing protein crystals; and a monitoring module for monitoring the protein crystals growing in the crystal growth module. The crystal growth module may comprise: a reservoir for accommodating a precipitant; and a plurality of capillaries for accommodating a protein solution, each capillary having one end positioned inside the reservoir. The monitoring module may comprise: a light-emitting module located on one side of the crystal growth module and configured to emit light toward the plurality of capillaries; and a detection module located on the other side of the crystal growth module and configured to detect light emitted from the light-emitting module.

Description

Protein crystal growth monitoring device

[0001] The present invention relates to a protein crystal growth monitoring device.

[0002] Structural studies of biopolymers, particularly proteins, are crucial for studying biological functions and developing structure-based medicines. Protein crystals are necessary for studying protein three-dimensional structures. Microscopes and other techniques are used to examine the state and properties of crystallized proteins. For example, optical microscopes, fluorescence microscopes, and electron microscopes can be used to observe crystallized proteins.

[0003] The above information may be provided as background art to aid in understanding the present disclosure. No claim or determination is made as to whether any of the above is applicable as prior art related to the present disclosure.

[0004] The present invention provides a protein crystal growth monitoring device capable of operating in microgravity, zero gravity and / or gravity environments.

[0005] In one embodiment, a protein crystal growth monitoring device may include a device case forming an internal space; a crystal growth module disposed inside the device case and for growing protein crystals; and a monitoring module disposed inside the device case and for monitoring protein crystals grown in the crystal growth module. The crystal growth module may include a crystal growth module frame; a reservoir positioned on one side of the crystal growth module frame and configured to accommodate a precipitant; and a plurality of capillaries having one end positioned inside the reservoir and configured to accommodate a protein solution. The monitoring module may include a light-emitting module positioned on one side of the crystal growth module and configured to emit light toward the plurality of capillaries; and a detection module positioned on the other side of the crystal growth module and configured to detect light emitted from the light-emitting module.

[0006] In one embodiment, the light-emitting module may include a light-emitting module frame and a plurality of light-emitting elements arranged in an array on the light-emitting module frame. The detection module may include a detection module frame and a plurality of detection elements arranged in an array on the detection module frame.

[0007] In one embodiment, at least some of the plurality of detection elements may include photodiodes.

[0008] In one embodiment, the detection module may further include a lens positioned between the photodiode and the capillary.

[0009] In one embodiment, at least some of the plurality of detection elements may include image sensors.

[0010] In one embodiment, the device may further include a temperature control module for controlling the temperature of the plurality of capillaries or the storage. The temperature control module may include a thermoelectric element positioned in at least one of the crystal growth module frame, the light emitting module frame, and the detection module frame; and a heat sink thermally connecting at least one of the crystal growth module frame, the light emitting module frame, and the detection module frame to the device case.

[0011] In one embodiment, the crystal growth module may further include a diaphragm positioned within the storage.

[0012] In one embodiment, the device may further include an assembly case for accommodating the crystal growth module and the monitoring module.

[0013] In one embodiment, the assembly case may further include a first buffer structure positioned on one side thereof; and a second buffer structure positioned on the other side thereof.

[0014] In one embodiment, the device may include a main circuit assembly configured to control the operation of the protein crystal growth monitoring device; and a connecting port formed on one surface of the device case for electrically connecting the main circuit assembly to an external device.

[0015] In one embodiment, a protein monitoring device can accurately observe and / or analyze crystallized proteins in microgravity, weightlessness, and / or gravity environments other than standard gravity on Earth.

[0016] The effects according to one embodiment are not limited to those mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

[0017] The above and other aspects, features and advantages of specific embodiments of the present invention will become more apparent from the following detailed description taken in conjunction with the accompanying drawings.

[0018] Figure 1 is a drawing illustrating an example of a method for protein crystallization.

[0019] Figure 2a is a diagram illustrating examples of different protein crystallization processes in a microgravity environment and an Earth gravity environment.

[0020] Figure 2b is a diagram illustrating an example of an experimental period on a space station.

[0021] FIG. 3A and FIG. 3B are diagrams illustrating an example of combining a protein monitoring module (100) and a protein crystal growth module (200) according to various embodiments of the present invention.

[0022] FIG. 4A and FIG. 4B are diagrams illustrating an example of a protein monitoring module (100) and a protein crystal growth module (200) according to various embodiments of the present invention.

[0023] FIG. 5 is a drawing illustrating an example of a protein crystal growth module (200) according to one embodiment of the present invention.

[0024] FIG. 6 is a diagram illustrating another example of a protein monitoring module (100) according to various embodiments of the present invention.

[0025] FIGS. 7A and 7B are diagrams illustrating an example of a device for monitoring a crystallized protein, according to various embodiments of the present invention.

[0026] FIG. 8A and FIG. 8B are diagrams illustrating another embodiment of a protein monitoring module (100) according to various embodiments of the present invention.

[0027] FIG. 9A is a perspective view of a protein crystal growth monitoring device according to one embodiment.

[0028] FIG. 9b is a perspective view of a protein crystal growth monitoring device according to one embodiment with the device case removed.

[0029] FIG. 9c is a perspective view of a crystal growth monitoring assembly according to one embodiment with the assembly case removed.

[0030] FIG. 9d is an exploded perspective view of a crystal growth module, a monitoring module, and a temperature control module according to one embodiment.

[0031] FIG. 9e is an exploded perspective view of a capillary and a reservoir of a crystal growth module according to one embodiment.

[0032] FIG. 9f is a cross-sectional view of a crystal growth module and a monitoring module according to one embodiment.

[0033] This patent application claims priority from Patent Application No. 2024-0119094, filed September 3, 2024, the entire contents of which are incorporated herein by reference.

[0034] Hereinafter, embodiments are described in detail with reference to the attached drawings. However, the embodiments may be modified in various ways, and the scope of the patent application is not limited or restricted by these embodiments. It should be understood that all modifications, equivalents, or alternatives to the embodiments are included within the scope of the patent application.

[0035] The terms used in the examples are for illustrative purposes only and should not be construed as limiting. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as "comprise" or "have" are intended to specify the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, but should be understood to not preclude the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0036] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the embodiments pertain. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and shall not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0037]

[0038] In addition, when describing with reference to the attached drawings, identical components will be assigned the same reference numerals regardless of the drawing numbers, and redundant descriptions thereof will be omitted. When describing embodiments, if a detailed description of a related known technology is judged to unnecessarily obscure the gist of the embodiment, the detailed description will be omitted.

[0039] Additionally, terms such as first, second, A, B, (a), (b), etc. may be used to describe components of the embodiments. These terms are only intended to distinguish the components from other components, and the nature, order, or sequence of the components are not limited by the terms. When a component is described as being "connected," "coupled," or "connected" to another component, it should be understood that the component may be directly connected or connected to the other component, but another component may also be "connected," "coupled," or "connected" between each component.

[0040] Components included in one embodiment and components with common functions will be described using the same names in other embodiments. Unless otherwise stated, the descriptions given in one embodiment may also apply to other embodiments, and detailed descriptions will be omitted to the extent of overlap.

[0041]

[0042] Hereinafter, embodiments disclosed in this specification will be described in detail with reference to the attached drawings. Regardless of the drawing reference numerals, identical or similar components will be assigned the same reference numerals, and redundant descriptions thereof will be omitted. Furthermore, when describing embodiments disclosed in this specification, if a detailed description of a related known technology is judged to obscure the gist of the embodiments disclosed in this specification, the detailed description thereof will be omitted.

[0043] Terms that include ordinal numbers, such as first, second, etc., may be used to describe various components, but the components are not limited by these terms. These terms are used solely to distinguish one component from another.

[0044] Singular expressions include plural expressions unless the context clearly indicates otherwise.

[0045] In this application, each step described may be performed regardless of the listed order, except in cases where a special causal relationship requires that the steps be performed in the listed order.

[0046] In this application, terms such as “include” or “have” are intended to specify the presence of a feature, number, step, operation, component, part or combination thereof described in the specification, but should be understood not to exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts or combinations thereof.

[0047]

[0048] According to various embodiments of the present invention, a device for monitoring crystallized proteins in a microgravity environment is described. Here, a microgravity environment may refer to a state in which the influence of gravity is very minimal. For example, a microgravity environment may occur within the International Space Station (ISS) or a spacecraft. Another example is a microgravity environment that occurs briefly during an aircraft's large parabolic trajectory. A further example is a microgravity environment that occurs briefly during the dropping of experimental equipment from a drop tower. A further example is a microgravity environment that occurs for a certain period of time during a rocket's ascent to an altitude near the edge of space and then subsequent fall back to Earth. In yet another example, a microgravity environment may persist while a protein crystallization device is in space.

[0049] According to various embodiments of the present invention, when crystallizing a protein using a protein crystallization device in a microgravity environment, various conditions may differ from those of the Earth's gravity environment. For example, in the Earth's gravity environment, convection, where air or liquid rises and falls due to temperature differences, typically occurs, which can affect temperature distribution and heat transfer. Furthermore, the resulting protein crystals can sediment due to gravity, affecting crystal-molecule interactions. In a microgravity environment, convection and sedimentation may rarely occur due to weak gravity. Because the microgravity environment eliminates distortion caused by gravity, more uniform and perfect crystal growth can occur.

[0050] Figure 1 is a drawing illustrating an example of a method for protein crystallization.

[0051] In one embodiment, the protein crystallization process can be performed by inserting an agarose gel or the like into a glass capillary tube. First, the glass capillary tube is vertically placed, and an agarose plug can be injected into one side of the glass capillary tube. Here, the agarose plug can be agarose in a gel form to prevent the protein solution and precipitant inside the glass capillary tube from leaking out. Thereafter, the protein solution can be injected into the glass capillary tube. The glass capillary tube can be sealed using beeswax or enamel.

[0052] Next, multiple sealed capillaries containing agarose plugs and protein solutions can be positioned within a space containing an agarose slug. The agarose slug can control the diffusion rate, allowing the protein solution and precipitant (e.g., salt) to mix slowly and uniformly, thereby facilitating crystallization. Furthermore, the agarose slug can form a concentration gradient, allowing the protein to reach supersaturation and contributing to physical stability.

[0053] Protein solutions and precipitants contained in glass capillaries can slowly diffuse over time. As the protein solution and precipitant diffuse, a concentration gradient is formed, and the protein reaches supersaturation, potentially leading to crystal formation. Subsequently, as the concentration gradient stabilizes, protein crystals can form.

[0054] In the initial state (T=0) for protein crystallization, a protein solution can be positioned in the capillary. Subsequently, during the diffusion initiation phase (T=1), the precipitant can diffuse toward the protein solution through the agarose slug. During the subsequent diffusion progression phase (T=2), the protein solution and precipitant can be slowly mixed to maintain a stable concentration gradient. Once the protein reaches supersaturation, crystal formation can begin. During the crystallization completion phase (T=4), the diffusion boundary can move across the entire capillary over time. Ultimately, as the concentration gradient stabilizes, protein crystals can form.

[0055] According to one embodiment, a counter diffusion method, a vapor diffusion method, a microdialysis method, etc. may be used as a method for protein crystallization.

[0056] Figure 2a is a diagram illustrating examples of different protein crystallization processes in a microgravity environment and an Earth gravity environment.

[0057] When protein crystallization is performed in a microgravity environment, a concentration gradient can be maintained. Because gravity is minimal in a microgravity environment, the protein solution and precipitant can diffuse slowly through the agarose slug. Furthermore, proteins crystallized in a microgravity environment produce large, clear crystals, and the protein crystals formed can be uniformly distributed throughout the capillary.

[0058] When performing protein crystallization in an Earth-gravity environment, disruption of the concentration gradient can occur. That is, the protein solution and precipitant can rapidly mix due to the influence of gravity in an Earth-gravity environment. Furthermore, the concentration gradient can be disrupted, leading to uneven diffusion. Furthermore, protein crystals formed in an Earth-gravity environment can form uneven and small crystals, and be unevenly distributed throughout the capillary.

[0059] Figure 2b is a diagram illustrating an example of an experimental period on a space station.

[0060] Looking at the experiment durations on the space station through the paper William E Lutz et. Al., Perfect Crystals: microgravity capillary counter diffusion crystallization of human manganese superoxide dismutase for neutron crystallography, npj Microgravity, (2023)9:39", the first experiment (SN001) on the space station took 40 days, the second experiment (SN002) took 263 days, the third experiment (SN003) took 33 days, and the fourth experiment (SN004) took 164 days.

[0061] In other words, experiments on protein crystallization and monitoring of crystallized proteins on the current space station may face difficulties in proceeding according to the planned schedule due to unexpected delays in the launch and recovery schedule of space launch vehicles. Therefore, experiments on protein crystallization and monitoring of crystallized proteins on the current space station are currently conducted using a method that manually controls the protein crystal growth time by varying the length of the agarose.

[0062] FIG. 3A and FIG. 3B are diagrams illustrating an example of combining a protein monitoring module (100) and a protein crystal growth module (200) according to various embodiments of the present invention.

[0063] Referring to FIG. 3A, according to one embodiment, the protein monitoring module (100) may include an upper housing (110), an upper lens mounting portion (120), and a lower lens mounting portion (130). Here, the protein monitoring module (100) is not limited to the above components, and some of the above components may be omitted or may include additional components.

[0064] The outer housing (101) of the protein monitoring module (100) may include a left housing (101a), a right housing (101b), and a lower housing (101c). For example, the left housing (101a) and the right housing (101b) may be configured as two sides of the outer housing (101). The lower housing (101c) may be configured to extend from one side of the left housing (101a) and from one side of the right housing (101b).

[0065] In one embodiment, the left housing (101a), the right housing (101b), and the lower housing (101c) may be an integrated structure that does not require separate assembly or joining. For example, the left housing (101a), the right housing (101b), and the lower housing (101c) may be manufactured by a method such as metal bending, injection molding, and / or extrusion molding. In another embodiment, the left housing (101a), the right housing (101b), and the lower housing (101c) may be configured as individual parts, and may be a structure that requires assembly. For example, the left housing (101a), the right housing (101b), and the lower housing (101c) may be joined to each other through a joining method such as screws, clips, and / or snap fits.

[0066] In one embodiment, the upper housing (110) may be mounted on one side of the protein monitoring module (100). The upper housing (110) may be coupled to an area between the left housing (101a) and the right housing (101b). For example, the inner surfaces of the left housing (101a) and the right housing (101b) may be provided with grooves or protrusions, and the upper housing (110) may be coupled to a protrusion corresponding to the groove or a groove corresponding to the protrusion. In another example, rails may be installed on the inner surfaces of the left housing (101a) and the right housing (101b), and the upper housing (110) may be coupled to the rails to be mounted. In another additional example, the upper housing (110) may be coupled to an area between the left housing (101a) and the right housing (101b) through a coupling method such as a screw, a clip, a snap fit, a magnet, and / or a hinge.

[0067] In one embodiment, the upper lens mounting portion (120) may be mounted on one side of the protein monitoring module (100). Additionally, the upper lens mounting portion (120) may be mounted at a distance adjacent to one side of the upper housing (110) mounted on the protein monitoring module (100) or in contact with the upper housing (110).

[0068] The upper lens mounting portion (120) may be coupled to an area between the left housing (101a) and the right housing (101b). For example, the upper lens mounting portion (120) may be coupled to a groove or a projection formed on the inner surface of the left housing (101a) and the right housing (101b), and a projection corresponding to the groove or a groove corresponding to the projection may be formed. In another example, a rail may be installed on the inner surface of the left housing (101a) and the right housing (101b), and the upper lens mounting portion (120) may be coupled to the rail to be mounted. In another additional example, the upper lens mounting portion (120) may be coupled to an area between the left housing (101a) and the right housing (101b) through a coupling method such as a screw, a clip, a snap fit, a magnetic and / or a hinge.

[0069] In one embodiment, the lower lens mounting portion (130) may be mounted on one side of the protein monitoring module (100). In addition, the lower lens mounting portion (130) may be mounted at a distance adjacent to one side of the lower housing (101c) mounted on the protein monitoring module (100) or in contact with the upper housing (110).

[0070] The lower lens mounting portion (130) may be coupled to an area between the left housing (101a) and the right housing (101b). For example, the lower lens mounting portion (130) may be coupled to a groove or a projection formed on the inner surface of the left housing (101a) and the right housing (101b), and a projection corresponding to the groove or a groove corresponding to the projection may be formed. In another example, a rail may be installed on the inner surface of the left housing (101a) and the right housing (101b), and the lower lens mounting portion (130) may be coupled to the rail to be mounted. In another additional example, the lower lens mounting portion (130) may be coupled to an area between the left housing (101a) and the right housing (101b) through a coupling method such as a screw, a clip, a snap fit, a magnet, and / or a hinge.

[0071] The protein crystal growth module (200) can be coupled to the protein monitoring module (100) in a detachable manner. For example, the way in which the protein crystal growth module (200) is coupled to the protein monitoring module (100) may be a cassette tape method in which the protein crystal growth module (200) is inserted and detached into a slot of the protein monitoring module (100). As another example, the way in which the protein crystal growth module (200) is coupled to the protein monitoring module (100) may be a slide rail method in which the protein crystal growth module (200) is inserted and detached along a rail of the protein monitoring module (100). As another additional example, the way in which the protein crystal growth module (200) is coupled to the protein monitoring module (100) may be through a snap-fit ​​method, a magnetic method, and / or a screw coupling method.

[0072] The protein crystal growth module (200) can be coupled to an area between the left housing (101a) and the right housing (101b) of the protein monitoring module (100). According to one embodiment, referring to FIG. 3b, steps (103a, 103b) for coupling the protein crystal growth module (200) can be formed on the inner surfaces of the left housing (101a) and the right housing (101b). The protein crystal growth module (200) can be coupled by inserting protrusions (201a, 201b) corresponding to the steps (103a, 103b).

[0073] According to another embodiment, a spring-movable protrusion or projection is formed on the inner surface of the left housing (101a) and the right housing (101b), and one side of the protein crystal growth module (200) is configured with a groove corresponding to the protrusion or projection so that they can be combined.

[0074] FIG. 4A and FIG. 4B are diagrams illustrating an example of a protein monitoring module (100) and a protein crystal growth module (200) according to various embodiments of the present invention.

[0075] FIG. 4a and FIG. 4b are cross-sectional drawings of the protein monitoring module (100) and protein crystal growth module (200) illustrated in FIG. 3a.

[0076] First, looking at the structure of the protein monitoring module (100), one side of the upper housing (110) of the protein monitoring module (100) may include a plurality of holes. The photodiode (111) may be a diode positioned in at least some of the holes to detect the light it receives. The upper lens mounting portion (120) of the protein monitoring module (100) may have an upper ball lens (121) and a bandpass filter (123) mounted on one side. Here, the upper ball lens (121) is a spherical optical lens that can focus or concentrate light from various directions. According to one embodiment, the upper ball lens (121) may be replaced with another lens that controls the path of light to focus or disperse it. Here, the bandpass filter (123) may be a filter that passes a specific frequency range (band) and blocks other frequencies.

[0077] The protein crystal growth module (200) may include a glass capillary (210). The protein crystal growth module (200) may be mounted on one side of the protein monitoring module (100). The lower lens mounting portion (130) of the protein monitoring module (100) may have a lower ball lens (131) mounted on one side. Here, the lower ball lens (131) is a spherical optical lens that can focus or concentrate light from various directions. The laser diode (133) may emit a light source at a preset angle so as not to affect light detection by the photodiode (111).

[0078] Looking at the function of the protein monitoring module (100) for monitoring the crystallized protein included in the protein crystal growth module (200), the laser diode (133) may be a device that generates a laser light source. The light source emitted from the laser diode (133) may be transmitted to the lower ball lens (131).

[0079] The protein crystal growth module (200) including a glass capillary (210) containing a protein crystallized through FIGS. 1 and 2A can receive light passing through the lower ball lens (131). The bandpass filter (123) can receive light passing through the protein crystal growth module (200). Here, the bandpass filter (123) can include a filter that passes or blocks only light of a specific wavelength. The upper ball lens (121) can receive light passing through the bandpass filter (123).

[0080] The photodiode (111) can confirm the size and / or shape of the crystallized protein contained in the glass capillary (210) by converting the received light into electricity. The photodiode performs the function of converting light into an electric signal, and a plurality of photodiodes can be configured to be arranged at regular intervals. The photodiode can include a diode that absorbs light to generate current, a signal processing circuit, etc. The photodiode can convert the light received from the upper ball lens (121) into current.

[0081] FIG. 5 is a drawing illustrating an example of a protein crystal growth module (200) according to one embodiment of the present invention.

[0082] The protein crystal growth module (200) may include a protrusion (201a, 201b), a glass capillary (210), an upper cover (220), a lower central cover (230), a lower cover (240), and a precipitant reservoir (250).

[0083] In one embodiment, the protrusions (201a, 201b) may be configured to be movable via a spring mechanism. For example, the protrusions (201a, 201b) may be equipped with a spring, such that when an external force is applied, they are positioned inside the protein crystal growth module (200), and when the external force is removed, they return to their original position. In the above example, the protrusions (201a, 201b) may be coupled by being inserted into a groove formed on at least one side of the protein monitoring module (100).

[0084] The glass capillary (210) may contain a protein solution. The glass capillary (210) may be mounted in a protein crystal growth module (200) in a manner in which a plurality of glass capillaries are arranged. An agarose gel (e.g., an agarose plug) may be positioned on the lower surface of the glass capillary (210).

[0085] The upper cover (220) may include a thermoelectric element for temperature control of the protein solution. For example, the upper cover (220) may include a Peltier element. Here, the Peltier element may have a characteristic in which one side absorbs heat and the other side releases heat when current flows.

[0086] The lower central cover (230) and the lower cover (240) may cover the lower surface of the protein crystal growth module (200) so as to be spaced apart from the upper cover (220). The lower central cover (230) and / or the lower cover (240) may include a thermoelectric device for controlling the diffusion rate of the solution. For example, the lower central cover (230) may include a Peltier device and / or thermoelectric modules.

[0087] The precipitant reservoir (250) may contain a precipitant. The precipitant is a substance used for protein crystallization and may include salts, organic solvents, neutral salts, polymers, and / or non-electrolytes. In one embodiment, the precipitant reservoir (250) may contain an agarose slug. The agarose slug may control the diffusion rate to slowly mix the protein solution and the precipitant, thereby providing a function for uniform crystallization.

[0088] Through the above configuration of the protein crystal growth module (200), temperature transfer between the agarose gel and the glass capillary (210) region can be blocked. For example, since the agarose gel and the glass capillary (210) have different thermal conductivity characteristics, a temperature imbalance may occur. However, through the upper cover (220), the lower central cover (230), and / or the lower cover (240) including a Peltier device that contributes to temperature control and solution diffusion rate control, the protein crystal growth reaction time included in the glass capillary (210) can be controlled.

[0089] FIG. 6 is a diagram illustrating another example of a protein monitoring module (100) according to various embodiments of the present invention.

[0090] According to one embodiment, the protein monitoring module (100) may include an LED array, an optical lens, an excitation optical filter, a crystallizer, an emission optical filter, and a photodiode array. Here, the protein monitoring module (100) is not limited to the above components, and some of the above components may be omitted or may include additional components.

[0091] In one embodiment, an LED array may be configured as a structure in which a plurality of light-emitting diodes (LEDs) are arranged. Here, the LED array may include an LED chip, which is a semiconductor device that emits light, a PCB substrate on which the LED chip is mounted, a resistor that controls the current flowing to the LED to maintain brightness, and / or a lens that diffuses or focuses the light of the LED in a specific direction. In addition, the LED array may be placed in a housing for heat management, power supply, wiring management, and / or optical design. For example, the LED array may be a high-power LED array, a surface-mount device LED, a chip-on-board LED, and / or a multi-chip module LED.

[0092] Here, the LED array of Fig. 6 is illustrated as a light source emitting vertically for convenience of explanation, but may be replaced with the lower ball lens (131) and laser diode (133) of Fig. 4b. In the above case, the LED array or laser diode (133) may be mounted at a preset angle or higher so as to emit light without affecting light detection by the photodiode (111).

[0093] In one embodiment, an optical lens may be mounted on one side of the LED array.

[0094] Here, the optical lens may be a collimating lens and / or a focusing lens.

[0095] In one embodiment, the collimating lens may be configured such that the distance between the light source and the lens and the arrangement of the lenses are determined so that the collimating lens performs the function of passing the light source parallel to the lens. For example, the collimating lens may be configured such that multiple spherical or planar lenses are aligned.

[0096] In one embodiment, the focusing lens may be configured to perform the function of focusing light onto a specific area, and the focal length of each lens may be determined to refract the light source. For example, the focusing lens may perform the function of having each of the arrayed lenses refract and focus light onto a specific focal point.

[0097] In one embodiment, light emitted from an LED array may be parallelized and transmitted to an excitation optical filter when passing through a collimating lens. In another embodiment, light emitted from an LED array may be focused to a specific region and transmitted to an excitation optical filter when passing through a focusing lens.

[0098] In one embodiment, the excitation optical filter may include a filter that selects a light source of a specific wavelength to excite a fluorescent material and emit light. For example, the excitation optical filter may select a specific wavelength from a broad spectrum of light sources to reach the fluorescent material, and the fluorescent material may perform the function of absorbing light of a specific wavelength and emitting light of a different wavelength.

[0099] In one embodiment, an excitation optical filter may receive light passing through an optical lens (e.g., a collimating lens and / or a focusing lens). The excitation optical filter may select a light source of a specific wavelength of the received light to excite a fluorescent material to emit light.

[0100] In one embodiment, the crystallizer may include a capillary tube containing a crystallized protein, as illustrated in FIGS. 1 and 2A . The crystallizer may include a plurality of capillary tubes. The crystallizer including the plurality of capillary tubes may receive light emitted by an excitation optical filter.

[0101] In one embodiment, the emission optical filter may include a filter that allows or blocks only light of a specific wavelength to pass through. For example, the emission optical filter may include a bandpass filter, a low pass filter, and / or a high pass filter. The emission optical filter may allow only light of a specific wavelength to pass through or block light received from the crystallizer.

[0102] According to one embodiment, a photodiode array may be a device that arranges multiple photodiodes. The photodiode array performs a function of converting light into an electrical signal, and may be configured such that a plurality of photodiodes are arranged at regular intervals. The photodiode array may include a photodiode that absorbs light to generate current, and a signal processing circuit, etc. The photodiode array may convert light received from an emission optical filter into current.

[0103] FIGS. 7A and 7B are diagrams illustrating an example of a device for monitoring a crystallized protein, according to various embodiments of the present invention.

[0104] The protein monitoring module (100) can check whether a protein is crystallized and / or the location of the crystallized protein, etc., through light received through a photodiode array when a protein is crystallized in a glass capillary tube included in a crystallizer. For example, when the protein monitoring module (100) receives light through a photodiode array, it can check the presence of a protein crystallized in a specific glass capillary tube. According to one embodiment, the protein monitoring module (100) can check the size and / or shape of a protein crystallized in a glass capillary tube included in a crystallizer as the light received by the photodiode array changes.

[0105] Referring to FIG. 7a, the protein monitoring module (100) can confirm the size and / or shape of a crystallized protein through a quenching detection method. Here, the quenching detection method is a method for detecting and measuring a phenomenon in which fluorescence or luminescence is suppressed, and may refer to a method for detecting a change in fluorescence intensity. The protein monitoring module (100) can detect a change in fluorescence intensity depending on the presence or absence, shape, and / or size of a protein crystallized in a glass capillary tube. Through this, the protein monitoring module (100) can confirm the presence, shape, and / or size of a crystallized protein.

[0106] Referring to FIG. 7b, the protein monitoring module (100) can confirm the size and / or shape of a crystallized protein through a fluorescence detection method. Here, the fluorescence detection method may refer to a method of detecting and measuring a phenomenon in which a fluorescent substance emits light. The protein monitoring module (100) can detect a change in fluorescence intensity depending on the presence, shape, and / or size of a crystallized protein in a glass capillary tube. Through this, the protein monitoring module (100) can confirm the presence, shape, and / or size of a crystallized protein.

[0107] FIG. 8A and FIG. 8B are diagrams illustrating another embodiment of a protein monitoring module (100) according to various embodiments of the present invention.

[0108] Referring to FIG. 8A, according to one embodiment, the protein monitoring module (100) may include a light source sensor (810), an optical component (820), and a light source (830). Here, the protein monitoring module (100) is not limited to the above components, and some of the above components may be omitted or may include additional components.

[0109] The protein crystal growth module (200) may be placed between the light source sensor (810) and the optical component (820). Here, the protein crystal growth module (200) may be placed at a preset adjacent position to the light source sensor (810).

[0110] In one embodiment, the light source sensor (810) may include a CMOS sensor (Complementary Metal-Oxide-Semiconductor). For example, the light source sensor (810) may be an image sensor that converts a light source into an electrical signal as a CMOS sensor to generate a digital image. The light source sensor (810) may include a pixel array, a charge-to-voltage converter, an amplifier, an ADC, and / or a controller. The light source sensor (810) may acquire a color image through an RGB sensor and detect an infrared image through an IR sensor. In addition, the light source sensor (810) may provide functions such as high-speed image capture, noise reduction, and / or WDR to provide high-quality images in various environments.

[0111] In one embodiment, the light source sensor (810) may be replaced with a CMOS sensor instead of the photodiode (111) of FIG. 4A. Here, the light source sensor (810) may be mounted in a multiple array structure on one side of the upper housing (110).

[0112] According to one embodiment, the optical component (820) may include at least one of a collimating lens, a focusing lens, a diffuser, and a filter. The lenses or filters constituting the optical component (820) may be partially omitted or may include additional components.

[0113] Here, the collimating lens may be configured such that the distance between the light source and the lens and / or the arrangement of the lenses are determined so that the collimating lens performs the function of passing the light source parallel. For example, the collimating lens may be configured such that multiple spherical or planar lenses are aligned. Here, the focusing lens may be configured such that the focal length of each lens is determined so that the light source is refracted and focused on a specific area. For example, the focusing lens may be configured such that each of the arranged lenses refracts the light and gathers it to a specific focal point. Here, the diffuser may evenly disperse the light source to provide soft, diffused lighting. Here, the filter may provide the function of passing or blocking light of a specific wavelength.

[0114] In one embodiment, the light source (830) may include an Organic Light Emitting Diode (OLED) and / or a Light Emitting Diode (LED), where OLED refers to a display technology that utilizes an organic light emitting diode, which may operate in a manner in which an organic compound emits light when an electric field is applied. Here, LED refers to a semiconductor light emitting diode, which may operate in a manner in which light is emitted when current flows.

[0115] Referring to FIG. 8B, one side of the upper housing (110) of the protein monitoring module (100) may include a plurality of holes. The light source sensor (810) may be positioned in at least some of the holes. Unlike FIG. 4A, the protein monitoring module (100) illustrated in FIG. 8B may omit components such as a ball lens and / or filter positioned in the upper lens mounting portion (120).

[0116] The protein crystal growth module (200) may include a glass capillary (210). The protein crystal growth module (200) may be mounted on one side of the protein monitoring module (100). For convenience of explanation, although not shown in FIG. 8B, at least one of a collimating lens, a focusing lens, a diffuser, and a filter constituting an optical component (820) may be positioned.

[0117] Looking at the function of the protein monitoring module (100) for monitoring the crystallized protein included in the protein crystal growth module (200), the light source (830) may be a device that generates light, such as an OLED or LED. The light emitted from the light source (830) may be transmitted to the optical component (820). Here, in order to monitor the crystallized protein, part or all of the light source (830) may blink.

[0118] A protein crystal growth module (200) including a glass capillary (210) containing a crystallized protein as shown in FIGS. 1 and 2A can receive light passing through an optical component (820). The light source sensor (810) converts the received light into electricity, thereby enabling the determination of the size and / or shape of the crystallized protein contained in the glass capillary (210).

[0119] Looking at existing monitoring modules, motorized microscope devices are currently used to monitor proteins crystallized in glass capillaries, as shown in Figures 1 and 2a, in a microgravity environment. Existing microgravity motorized microscope devices require power for movement control. For example, the size of the device containing the crystallized protein is larger than the microscope device itself, so movement of either the microscope device or the device containing the crystallized protein is essential to observe the entire device containing the crystallized protein. Furthermore, when using a motorized microscope device, there is a risk of unnecessary noise generation or errors.

[0120] The protein monitoring module (100) disclosed in FIGS. 3A to 6 has the technical advantage of enabling more accurate and efficient identification of crystallized proteins by monitoring crystallized proteins without using a motor. For example, the protein monitoring module (100) disclosed in FIGS. 3A to 6 does not require a motor requiring power, and has the advantage of enabling more accurate observation of crystallized proteins while reducing unnecessary noise generation and the possibility of errors through simpler components.

[0121] In addition, the protein monitoring module (100) illustrated in FIG. 8b can simultaneously measure signals of multiple wavelengths by four diodes (RGB, UV / IR) through a CMOS image sensor, which is a light source sensor (810). In addition, the protein monitoring module (100) can be integrated into a single CMOS image sensor without the need to solder individual photodiodes, thereby achieving structural simplification. In addition, the protein monitoring module (100) can analyze 2D images by using a CMOS image sensor, and reliability can be improved.

[0122]

[0123] FIG. 9A is a perspective view of a protein crystal growth monitoring device according to one embodiment. FIG. 9B is a perspective view of a protein crystal growth monitoring device according to one embodiment with the device case removed.

[0124] Referring to FIGS. 9A and 9B , a protein crystal growth monitoring device (1) according to an embodiment may be a device for growing protein crystals and monitoring the grown protein crystals. For example, the protein crystal growth monitoring device (1) may be operated in a microgravity, zero gravity, and / or gravity environment. For example, the protein crystal growth monitoring device (1) may be operated inside the International Space Station (ISS) or a spacecraft. For example, the protein crystal growth monitoring device (1) may be operated while a rocket or an airplane is falling, or while the device is falling from a drop tower or a building. For example, the protein crystal growth monitoring device (1) may be configured to proceed with protein crystallization without the intervention of an outside person (e.g., an astronaut) and automatically generate experimental data accordingly. However, this is exemplary, and the protein crystal growth monitoring device (1) may also be operated under general gravity.

[0125] In one embodiment, a protein crystal growth monitoring device (1) may include a device case (10), a crystal growth monitoring assembly (2), a first buffer structure (11), a second buffer structure (12), a main circuit assembly (13), and / or a connecting port (not shown).

[0126] In one embodiment, the device case (10) may form at least a portion of the exterior of the protein crystal growth monitoring device (1). The device case (10) may form an internal space in which each component of the protein crystal growth monitoring device (1) is arranged. For example, the device case (10) may have a hexahedral shape.

[0127] In one embodiment, the crystal growth monitoring assembly (2) may be disposed inside the device case (10). The crystal growth monitoring assembly (2) may be an assembly for growing protein crystals and monitoring the grown protein crystals. The crystal growth monitoring assembly (2) may include an assembly case (20). The assembly case (20) may form an internal space for arranging each component of the crystal growth monitoring assembly (2). The assembly case (20) may accommodate at least a crystal growth module (3) and a monitoring module (4) described below. For example, the assembly case (20) may have a hexahedral shape.

[0128] In one embodiment, the first buffer structure (11) and the second buffer structure (12) may be disposed inside the device case (10). The first buffer structure (11) and the second buffer structure (12) may be configured to buffer an impact applied to the crystal growth monitoring assembly (2). For example, the first buffer structure (11) may be positioned on one side (e.g., the lower side) of the assembly case (20), and the second buffer structure (12) may be positioned on the other side (e.g., the upper side) of the assembly case (20). The first buffer structure (11) and the second buffer structure (12) may include a structure for absorbing an impact. For example, the first buffer structure (11) and the second buffer structure (12) may include a porous member and / or a porous frame. However, this is an example, and the structures of the first buffer structure (11) and the second buffer structure (12) are not limited thereto, and the first buffer structure (11) and the second buffer structure (12) may include various structures for absorbing shock.

[0129] In one embodiment, the main circuit assembly (13) may be disposed inside the device case (10). For example, the main circuit assembly (13) may be located at the lower end (e.g., the -Z direction end) of the device case (10). The main circuit assembly (13) may be configured to control the operation of the protein crystal growth monitoring device (1). For example, the main circuit assembly (13) may include a printed circuit board, a processor, a memory, active components, and / or passive components. For example, the main circuit assembly (13) may include a communication module for transmitting data measured by the protein crystal growth monitoring device (1) to the outside and / or receiving data from the outside. A connecting port (not shown) may be formed on one surface of the device case (10) to electrically connect the main circuit assembly (13) to an external device. For example, the connecting port may be formed on the lower surface (e.g., the -Z direction surface) of the device case (10).

[0130]

[0131] FIG. 9C is a perspective view of a crystal growth monitoring assembly according to one embodiment with the assembly case removed. FIG. 9D is an exploded perspective view of a crystal growth module, a monitoring module, and a temperature control module according to one embodiment. FIG. 9E is an exploded perspective view of a capillary and a reservoir of a crystal growth module according to one embodiment. FIG. 9F is a cross-sectional view of a crystal growth module and a monitoring module according to one embodiment.

[0132] Referring to FIGS. 9C to 9F, in one embodiment, the crystal growth monitoring assembly (2) may include an assembly case (e.g., 20 of FIG. 9B), a crystal growth module (3) (e.g., a protein crystal growth module (200) of FIGS. 3A, 3B, 4A, 4B, 5, 8A and / or 8B), a monitoring module (4) (e.g., a protein monitoring module (100) of FIGS. 3A, 3B, 4A, 4B, 8A and / or 8B), a temperature control module (7), and an assembly control circuit (8).

[0133] In one embodiment, the crystal growth module (3) may be a module for growing protein crystals. The crystal growth module (3) may include a crystal growth module frame (31), a capillary (32) (e.g., a glass capillary (210) of FIG. 4A, FIG. 5, and / or FIG. 8B), a reservoir (33) (e.g., a precipitant reservoir (250) of FIG. 5), and / or a diaphragm (34).

[0134] In one embodiment, the crystal growth module frame (31) may provide a space for arranging each component of the crystal growth module (3). For example, the crystal growth module frame (31) may include a metal material. For example, the crystal growth module frame (31) may include a first crystal growth module frame (311) and a second crystal growth module frame (312). For example, the first crystal growth module frame (311) and the second crystal growth module frame (312) may be substantially understood as a lower plate and an upper plate, respectively. The first crystal growth module frame (311) and the second crystal growth module frame (312) may include grooves, recesses, holes, and / or steps for arranging a capillary (32), a reservoir (33), and / or a diaphragm (34). For example, the capillary (32) may be substantially arranged between the first crystal growth module frame (311) and the second crystal growth module frame (312).

[0135] In one embodiment, the crystal growth module frame (31) may include a first hole (313), a second hole (314), a third hole (315), and a fourth hole (316). The first hole (313), the second hole (314), the third hole (315), and / or the fourth hole (316) may allow the first capillary (32a) and / or the second capillary (32b) disposed between the first crystal growth module frame (311) and the second crystal growth module frame (312) to be exposed toward the light emitting module (5) and / or the detection module (6). The first hole (313), the second hole (314), the third hole (315), and the fourth hole (316) may be provided in a single or multiple number, respectively. Each of the plurality of first holes (313), the plurality of second holes (314), the plurality of third holes (315) and the plurality of fourth holes (316) can be arranged in an array form.

[0136] In one embodiment, the first hole (313) and the second hole (314) may be formed in the first region (A1) of the crystal growth module frame (31). For example, the first hole (313) may be formed in the first crystal growth module frame (311), and the second hole (314) may be formed in the second crystal growth module frame (312). The first hole (313) and the second hole (314) may substantially provide a path for light generated from the first light-emitting element (52a). For example, the first hole (313) may be formed to be inclined at substantially 45 degrees with respect to a horizontal plane (e.g., XY plane). For example, the second hole (314) may be formed to be inclined at substantially 45 degrees with respect to a horizontal plane (e.g., XY plane). For example, the second hole (314) may be formed to be inclined in the opposite direction to the first hole (313). For example, the first hole (313) and the second hole (314) can form a substantially 90-degree angle. One side (e.g., the lower side) of the first capillary (32a) can be exposed toward the light-emitting module (5) (e.g., the first light-emitting element (52a)) through the first hole (313), and the other side (e.g., the upper side) of the first capillary (32a) can be exposed toward the detection module (6) (e.g., the lens (63) and the photodiode (62a)) through the second hole (314).

[0137] In one embodiment, the third hole (315) and the fourth hole (316) may be formed in the second region (A2) of the crystal growth module frame (31). For example, the third hole (315) may be formed in the first crystal growth module frame (311), and the fourth hole (316) may be formed in the second crystal growth module frame (312). The third hole (315) and the fourth hole (316) may substantially provide a path for light generated from the second light-emitting element (52b). For example, the third hole (315) and the fourth hole (316) may be formed in a substantially vertical direction (e.g., Z direction). One side (e.g., the lower side) of the second capillary (32b) may be exposed toward the light-emitting module (5) (e.g., the second light-emitting element (52b)) through the third hole (315), and the other side (e.g., the upper side) of the second capillary (32b) may be exposed toward the detection module (6) (e.g., the image sensor (62b)) through the fourth hole (316). However, this is merely exemplary, and the structure and / or arrangement of the first hole (313), the second hole (314), the third hole (315), and the fourth hole (316) is not limited thereto.

[0138] In one embodiment, the storage (33) may be located at one side (e.g., the +Y direction portion) of the crystal growth module frame (31). The storage (33) may provide a space for accommodating a precipitant. The storage (33) may include a first cover (331), a storage frame (332), and / or a second cover (334). The storage frame (332) may form a storage space (333) for accommodating a precipitant. For example, the storage space (333) may include a first storage space (333a) and a second storage space (333b) that are partitioned from each other. For example, the first storage space (333a) and the second storage space (333b) may be positioned to be spaced apart from each other in the width direction (e.g., the X direction) of the storage frame (332). The first cover (331) and the second cover (334) can close the storage space (333) of the storage frame (332). The first cover (331) and the second cover (334) can be positioned on one side (e.g., +Y direction portion) and the other side (e.g., -Y direction portion) of the storage frame (332), respectively. However, this is exemplary, and the structure of the storage (33) is not limited thereto.

[0139] In one embodiment, the diaphragm (34) may be positioned inside the reservoir (33). For example, the diaphragm (34) may be positioned at the lower end (e.g., the +Y direction end) of the reservoir (33). The diaphragm (34) may include a flexible membrane member. The diaphragm (34) may respond to changes in the volume of the liquid contained in the reservoir.

[0140] In one embodiment, the capillary (32) may be configured to receive a protein solution. The capillary (32) may include a tubular shape having a longitudinal direction (e.g., Y direction). For example, the capillary (32) may have a substantially cylindrical or rectangular cylindrical shape. For example, the capillary (32) may be formed of a light-transmitting material. For example, the capillary (32) may be a glass capillary. One end (e.g., +Y direction end) of the capillary (32) may be positioned inside the reservoir (33). For example, one end (e.g., +Y direction end) of the capillary (32) may be positioned to penetrate the second cover (334). A gasket may be positioned in the area where the capillary (32) penetrates the second cover (334). For example, an agarose plug may be positioned at one end (e.g., +Y direction end) of the capillary (32). For example, the other end of the capillary (32) (e.g., the -Y direction end) can be closed with a sealing member.

[0141] In one embodiment, a plurality of capillaries (32) may be provided. The plurality of capillaries (32) may be arranged in parallel to each other. For example, the plurality of capillaries (32) may include a first capillary (32a) and a second capillary (32b). The first capillary (32a) and the second capillary (32b) may be provided singly or in plurality. The first capillary (32a) may be arranged in a first area (A1) of the crystal growth module frame (31), and the second capillary (32b) may be arranged in a second area (A2) of the crystal growth module frame (31). For example, the first capillary (32a) may be arranged between the first hole (313) and the second hole (314), and the second capillary (32b) may be arranged between the third hole (315) and the fourth hole (316).

[0142] In one embodiment, the first capillary (32a) and the second capillary (32b) may be arranged at different orientation angles. For example, the orientation angles of the first capillary (32a) and the second capillary (32b) may differ by substantially 45 degrees. For example, when the first capillary (32a) and the second capillary (32b) are each in the shape of a square column, the first capillary (32a) may be arranged such that some corners of the square column face downward (e.g., -Z direction) and upward (e.g., +Z direction), and the second capillary (32b) may be arranged such that some faces of the square column face downward (e.g., -Z direction) and upward (e.g., +Z direction). However, this is merely exemplary, and the arrangement of the first capillary (32a) and the second capillary (32b) is not limited thereto.

[0143] In one embodiment, the monitoring module (4) may be a module for monitoring protein crystals grown in the crystal growth module (3). The monitoring module (4) may include a luminescence module (5) and a detection module (6). The luminescence module (5) and the detection module (6) may be positioned so that the crystal growth module (3) is positioned therebetween. For example, the luminescence module (5) may be positioned on one side (e.g., the -Z direction portion) of the crystal growth module (3), and the detection module (6) may be positioned on the other side (e.g., the +Z direction portion) of the crystal growth module (3). For example, the luminescence module (5), the crystal growth module (3), and the detection module (6) may be sequentially stacked. For example, the luminescence module (5), the crystal growth module (3), and the detection module (6) may be fixedly connected to each other by a fastening member. For example, the luminescence module frame (51), the crystal growth module frame (31), and the detection module frame (61) may be fixedly connected to each other by a fastening member.

[0144] In one embodiment, the light emitting module (5) may be configured to emit light toward a plurality of capillaries (32). The light emitting module (5) may include a light emitting module frame (51) and a light emitting element (52).

[0145] In one embodiment, the light emitting module frame (51) may provide a space for arranging each component of the light emitting module (5). For example, the light emitting module frame (51) may include a metal material. For example, the light emitting module frame (51) may be positioned on one side (e.g., a -Z direction portion) of the crystal growth module frame (31). For example, the light emitting module frame (51) may include a first light emitting module frame (511) and a second light emitting module frame (512). For example, the first light emitting module frame (511) and the second light emitting module frame (512) may be understood as a lower plate and an upper plate, respectively. The first light emitting module frame (511) and the second light emitting module frame (512) may include grooves, recesses, holes, and / or steps for arranging the light emitting element (52), the circuit board, and / or the thermoelectric element (72).

[0146] In one embodiment, the light emitting module frame (51) may include a plurality of light emitting holes (513) for arranging a plurality of light emitting elements (52). At least some of the plurality of light emitting holes (513) may be arranged in an array form. For example, the plurality of light emitting holes (513) may include a first light emitting hole (513a) and a second light emitting hole (513b). The first light emitting hole (513a) and the second light emitting hole (513b) may be provided singly or in plurality. The first light emitting hole (513a) may be formed in a first region (A1) of the light emitting module frame (51), and the second light emitting hole (513b) may be formed in a second region (A2) of the light emitting module frame (51).

[0147] In one embodiment, the first light-emitting hole (513a) may be a hole in which the first light-emitting element (52a) described below is arranged. For example, the first light-emitting hole (513a) may be formed across the first light-emitting module frame (511) and the second light-emitting module frame (512). The first light-emitting hole (513a) may substantially provide a path for light generated from the first light-emitting element (52a). For example, the first light-emitting hole (513a) may be formed to be inclined at a substantially 45 degree angle with respect to a horizontal plane (e.g., an XY plane). The first light-emitting hole (513a) may be formed in substantially the same direction as the first hole (313). The first light-emitting hole (513a) may be in communication with the first hole (313).

[0148] In one embodiment, the second light-emitting hole (513b) may be a hole in which the second light-emitting element (52b) described below is arranged. For example, the second light-emitting hole (513b) may be formed in the second light-emitting module frame (512). The second light-emitting hole (513b) may substantially provide a path for light generated from the second light-emitting element (52b). For example, the second light-emitting hole (513b) may be formed in a substantially vertical direction (e.g., Z direction). The second light-emitting hole (513b) may be in communication with the third hole (315). However, this is merely exemplary, and the structure and / or arrangement of the first light-emitting hole (513a) and the second light-emitting hole (513b) are not limited thereto.

[0149] In one embodiment, the light emitting element (52) may be configured to emit light toward a plurality of capillaries (32). For example, the light emitting element (52) may include a laser diode (LD) and / or a light emitting diode (LED). However, this is merely exemplary, and the light emitting element (52) is not limited thereto. The light emitting element (52) may be provided in plurality. The plurality of light emitting elements (52) may be arranged in an array form. For example, the plurality of light emitting elements (52) may be arranged to be spaced apart from each other along the longitudinal direction (e.g., Y direction) of the capillary (32) for each capillary (32).

[0150] In one embodiment, the plurality of light-emitting elements (52) may include a first light-emitting element (52a) and a second light-emitting element (52b). The first light-emitting element (52a) and the second light-emitting element (52b) may be provided in a single or multiple number. The first light-emitting element (52a) may be arranged in a first area (A1) of the light-emitting module frame (51), and the second light-emitting element (52b) may be arranged in a second area (A2) of the light-emitting module frame (51). The first light-emitting element (52a) may be arranged in a first light-emitting hole (513a), and the second light-emitting element (52b) may be arranged in a second light-emitting hole (513b).

[0151] In one embodiment, the first light-emitting element (52a) can emit light toward the first capillary (32a), and the second light-emitting element (52b) can emit light toward the second capillary (32b). The first light-emitting element (52a) and the second light-emitting element (52b) can be arranged at different orientation angles. For example, the orientation angles of the first light-emitting element (52a) and the second light-emitting element (52b) can differ by substantially 45 degrees. For example, the first light-emitting element (52a) can emit light at an angle substantially inclined at 45 degrees with respect to a vertical direction (e.g., a Z direction), and the second light-emitting element (52b) can emit light in a substantially vertical direction (e.g., a Z direction). However, this is exemplary, and the arrangement of the light-emitting elements (52) is not limited thereto.

[0152] In one embodiment, the detection module (6) may be configured to detect light generated from the light emitting module (5). The detection module (6) may acquire data on protein crystals. The detection module (6) may include a detection module frame (61), a detection element (62), and a lens (63).

[0153] In one embodiment, the detection module frame (61) may provide a space for arranging each component of the detection module (6). For example, the detection module frame (61) may include a metal material. For example, the detection module frame (61) may be positioned on the other side (e.g., the +Z direction portion) of the crystal growth module frame (31). For example, the detection module frame (61) may include a first detection module frame (611) and a second detection module frame (612). For example, the first detection module frame (611) and the second detection module frame (612) may be understood as substantially a lower plate and an upper plate, respectively. The first detection module frame (611) and the second detection module frame (612) may include grooves, recesses, holes, and / or steps for arranging the detection element (62), the lens (63), and / or the circuit board.

[0154] In one embodiment, the detection module frame (61) may include a plurality of detection holes (613) for arranging a plurality of detection elements (62) and / or a plurality of lenses (63). At least some of the plurality of detection holes (613) may be arranged in an array form. For example, the plurality of detection holes (613) may include a first detection hole (613a) and a second detection hole (613b). The first detection hole (613a) and the second detection hole (613b) may be provided singly or in plurality. The first detection hole (613a) may be formed in a first area (A1) of the detection module frame (61), and the second detection hole (613b) may be formed in a second area (A2) of the detection module frame (61).

[0155] In one embodiment, the first detection hole (613a) may be a hole for arranging a photodiode (62a) and / or a lens (63) described below. For example, the first detection hole (613a) may be formed across the first detection module frame (611) and the second detection module frame (612). The first detection hole (613a) may substantially provide a path for light generated from the first light-emitting element (52a). For example, the first detection hole (613a) may be formed to be inclined at a substantially 45 degree angle with respect to a horizontal plane (e.g., an XY plane). For example, the first detection hole (613a) may be formed to be inclined in a direction opposite to that of the first light-emitting hole (513a). For example, the first detection hole (613a) and the first light-emitting hole (513a) may form a substantially 90 degree angle. The first detection hole (613a) can be connected to the second hole (314).

[0156] In one embodiment, the second detection hole (613b) may be a hole for arranging the image sensor (62b) described below. For example, the second detection hole (613b) may be formed in the first detection module frame (611). For example, the second detection hole (613b) may be formed in a substantially vertical direction (e.g., in the Z direction). The second detection hole (613b) may be in communication with the fourth hole (316). However, this is merely exemplary, and the structure and / or arrangement of the first detection hole (613a) and the second detection hole (613b) are not limited thereto.

[0157] In one embodiment, the detection element (62) may be configured to detect light generated from the light-emitting element (52). For example, the detection element (62) may be provided in a plurality. The plurality of detection elements (62) may be arranged in an array form. For example, the plurality of detection elements (62) may be arranged spaced apart from each other along the longitudinal direction (e.g., Y direction) of the capillary (32) for each capillary (32). For example, the plurality of detection elements (62) may be provided in a number corresponding to the plurality of light-emitting elements (52). For example, the plurality of detection elements (62) may be positioned at positions corresponding to the plurality of light-emitting elements (52).

[0158] In one embodiment, the plurality of detection elements (62) may include a photodiode (62a) and an image sensor (62b). For example, at least some of the plurality of detection elements (62) may include a photodiode (62a). For example, at least some of the plurality of detection elements (62) may include an image sensor (62b). The photodiode (62a) and the image sensor (62b) may be provided singly or in plurality. The photodiode (62a) may be arranged in a first area (A1) of the detection module frame (61), and the image sensor (62b) may be arranged in a second area (A2) of the detection module frame (61). The photodiode (62a) may be arranged in a first detection hole (613a), and the image sensor (62b) may be arranged in a second detection hole (613b). For example, a photodiode (62a) can detect light generated from a first light-emitting element (52a), and an image sensor (62b) can detect light generated from a second light-emitting element (52b).

[0159] In one embodiment, the lens (63) may be positioned between the photodiode (62a) and the capillary (32) (e.g., the first capillary (32a)). The lens (63) may be positioned in the first area (A1) of the detection module frame (61). The lens (63) may be positioned in the first detection hole (613a). The number of lenses (63) may correspond to the number of photodiodes (62a). For example, the lens (63) may include a ball lens. However, this is exemplary, and the type of the lens (63) is not limited thereto.

[0160] In one embodiment, a first light-emitting element (52a), a first capillary (32a), a lens (63), and a photodiode (62a) may be arranged in the first region (A1). In the first region (A1), the photodiode (62a) may obtain information on protein crystals using dynamic light scattering (DLS). For example, light generated from the first light-emitting element (52a) may be transmitted to the first capillary (32a) through the first light-emitting hole (513a) and the first hole (313). The light transmitted to the first capillary (32a) may be scattered by the protein crystals inside the first capillary (32a). The scattered light may be transmitted through the second hole (314) and the first detection hole (613a), collected through the lens (63), and detected by the photodiode (62a). For example, a processor (not shown) can analyze changes in light intensity measured by a photodiode (62a) to calculate the size and / or distribution of protein crystals.

[0161] In one embodiment, a second light-emitting element (52b), a second capillary (32b), and an image sensor (62b) may be arranged in the second region (A2). In the second region (A2), the image sensor (62b) may obtain image information on protein crystals. For example, light generated from the second light-emitting element (52b) may be transmitted to the second capillary (32b) through the second light-emitting hole (513b) and the third hole (315). The light transmitted to the second capillary (32b) may be reflected by the protein crystals inside the second capillary (32b). The reflected light may be transmitted through the fourth hole (316) and detected by the image sensor (62b). For example, a processor (not shown) may convert information detected by the image sensor (62b) into a visual image.

[0162] Meanwhile, in explaining one embodiment, it is explained that both a first area (A1) for using a dynamic light scattering method and a second area (A2) for obtaining image information exist, but this is exemplary, and in one embodiment, only a first area (A1) for using a dynamic light scattering method or only a second area (A2) for obtaining image information may exist.

[0163] In one embodiment, the temperature control module (7) may be a module for controlling the temperature of the crystal growth monitoring assembly (2). For example, the temperature control module (7) may be a module for controlling the temperature of a plurality of capillaries (32) and / or reservoirs (33). The temperature control module (7) may be configured to be capable of generating heat or cooling. By controlling the temperature of the plurality of capillaries (32) and / or reservoirs (33) using the temperature control module (7), the rate of protein crystallization and / or the rate of diffusion of the precipitant may be controlled.

[0164] In one embodiment, the temperature control module (7) may include a temperature sensor (not shown), a thermoelectric element (72), and a heat sink (73).

[0165] In one embodiment, a temperature sensor (not shown) may be configured to measure the temperature of the crystal growth monitoring assembly (2). For example, the temperature sensor may be configured to measure the temperature of a plurality of capillaries (32) and / or reservoirs (33). For example, a single or multiple temperature sensors may be provided. For example, the temperature sensor may be located in at least one of the crystal growth module frame (31), the light emitting module frame (51), and the detection module frame (61). For example, the temperature sensor may be positioned in a groove formed on the outer periphery of the first light emitting module frame (511).

[0166] In one embodiment, the thermoelectric element (72) may be configured to generate heat or cool. For example, the thermoelectric element (72) may include a Peltier element. For example, the thermoelectric element (72) may be provided singly or in multiples. The thermoelectric element (72) may be positioned in at least one of the crystal growth module frame (31), the light emitting module frame (51), and the detection module frame (61). For example, the thermoelectric element (72) may be positioned in the outer region of the first light emitting module frame (511).

[0167] In one embodiment, the heat sink (73) can provide a path for dissipating heat inside the crystal growth monitoring assembly (2) to the outside of the protein crystal growth monitoring device (e.g., 1 of FIG. 9A). For example, the heat sink (73) can thermally connect at least one of the crystal growth module frame (31), the light emitting module frame (51), and the detection module frame (61) to the device case (e.g., 10 of FIG. 9A). For example, one end of the heat sink (73) can be in contact with at least one of the crystal growth module frame (31), the light emitting module frame (51), and the detection module frame (61), and the other end of the heat sink (73) can be in contact with one surface of the device case (10). For example, one end of the heat sink (73) can be positioned on the light emitting module frame (51), and the crystal growth module frame (31) and the detection module frame (61) can be thermally connected to each other with the light emitting module frame (51). For example, one end of the heat sink (73) may be connected to the heating surface of the thermoelectric element (72). At least a portion of the heat sink (73) may penetrate the assembly case (e.g., 20 in FIG. 9b). With this structure, heat generated in at least one of the crystal growth module frame (31), the light emitting module frame (51), and the detection module frame (61) may be discharged to the device case (10) through the heat sink (73).

[0168] In one embodiment, the assembly control circuit (8) may be disposed inside the assembly case (e.g., 20 of FIG. 9b). For example, the assembly control circuit (8) may be located at the lower end (e.g., the -Z direction end) of the assembly case (20). The assembly control circuit (8) may be configured to control the operation of the crystal growth monitoring assembly (2). For example, the assembly control circuit (8) may include a printed circuit board, a processor, a memory, active components, and / or passive components. For example, the assembly control circuit (8) may include a communication module for transmitting data measured in the crystal growth monitoring assembly (2) to the outside and / or receiving data from the outside. However, this is exemplary, and the location of the assembly control circuit (8) is not limited thereto. For example, at least a portion of the assembly control circuit (8) may be provided in the light emitting module frame (51) and / or the detection module frame (61) to control the operation of the light emitting module (5), the detection module (6) and / or the temperature control module (7).

[0169] In one embodiment, the crystal growth monitoring assembly (2) may further include an additional crystal growth module (3-1) that is provided separately from the above-described crystal growth module (3). For example, the additional crystal growth module (3-1) may be a module that is not monitored by the monitoring module (4). For example, the additional crystal growth module (3-1) may be located at the upper end (e.g., the +Z direction end) of the crystal growth monitoring assembly (2). The additional crystal growth module (3-1) may have substantially the same structure as the above-described crystal growth module (3). The additional crystal growth module (3-1) may be provided singly or in plurality. For example, the additional crystal growth module (3-1) may include first to third additional crystal growth modules (3-1a, 3-1b 3-1c). The first to third additional crystal growth modules (3-1a, 3-1b 3-1c) may be arranged in a stacked form. However, this is an example, and the placement of the additional crystal growth module (3-1) is not limited to this.

[0170] In one embodiment, the protein crystal growth monitoring device (1) and / or the crystal growth monitoring assembly (2) may further include a spacer that separates the respective components from each other.

[0171] Meanwhile, it will be readily apparent to those skilled in the art that the embodiments described through FIGS. 9a to 9f can be combined with the embodiments described through FIGS. 1 to 8b within a range that does not conflict with each other.

[0172]

[0173] The technical features disclosed in each embodiment of the present invention are not limited to that embodiment, and, unless they are mutually incompatible, the technical features disclosed in each embodiment may be combined and applied to different embodiments. Those skilled in the art will further understand that any disjunctive words and / or phrases indicating two or more alternative terms, whether in the detailed description, claims, or drawings of the present invention, are to be understood to contemplate the possibility of including one of the terms, either of the terms, or both of the terms. For example, the phrase "A or B" is to be understood to encompass the possibility of "A" or "B," or "A and B." Furthermore, as used herein, the term "each," in addition to its ordinary meaning, may mean any subset of the set of elements to which the term "each" applies. Combinatory language such as the phrase "at least one of X, Y, and Z," unless specifically stated otherwise, is to be understood in the context in which it is generally used to convey that an item, term, etc., can be X, Y, or Z. Thus, such binding language is generally not intended to imply that a particular embodiment requires the presence of at least one of X, at least one of Y, or at least one of Z.

[0174] Accordingly, each embodiment focuses on its respective technical features. However, unless the technical features are incompatible, they can be combined and applied. The present invention is not limited to the above-described embodiments and the attached drawings, and various modifications and variations are possible from the perspective of those skilled in the art. Therefore, the scope of the present invention should be defined not only by the claims of this specification but also by equivalents thereof.

[0175]

[0176] Although the embodiments described above have been described with limited drawings, those skilled in the art will appreciate that various technical modifications and variations can be applied based on the above. For example, appropriate results can still be achieved even if the described techniques are performed in a different order than described, and / or components of the described systems, structures, devices, circuits, etc. are combined or combined in a different manner than described, or are replaced or substituted with other components or equivalents.

[0177] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims described below.

Claims

1. In a protein crystal growth monitoring device, A device case forming an internal space; A crystal growth module for growing protein crystals, which is placed inside the device case; and A monitoring module is disposed inside the device case and includes a monitoring module for monitoring protein crystals grown in the crystal growth module, The above crystal growth module is, Crystal growth module frame; A storage located on one side of the above crystal growth module frame and for receiving a precipitant; and One end is positioned inside the reservoir and includes a plurality of capillaries for receiving a protein solution, The above monitoring module, A light-emitting module positioned on one side of the crystal growth module and configured to emit light toward the plurality of capillaries; and A protein crystal growth monitoring device comprising a detection module positioned on the other side of the crystal growth module and configured to detect light generated from the light-emitting module.

2. In paragraph 1, The above light-emitting module includes a light-emitting module frame and a plurality of light-emitting elements arranged in an array form on the light-emitting module frame, A protein crystal growth monitoring device, wherein the detection module comprises a detection module frame and a plurality of detection elements arranged in an array form on the detection module frame.

3. In paragraph 2, A protein crystal growth monitoring device, wherein at least some of the plurality of detection elements include photodiodes.

4. In paragraph 3, A protein crystal growth monitoring device, wherein the detection module further includes a lens positioned between the photodiode and the capillary.

5. In paragraph 2, A protein crystal growth monitoring device, wherein at least some of the plurality of detection elements include an image sensor.

6. In paragraph 2, Further comprising a temperature control module for controlling the temperature of the plurality of capillaries or the storage, The above temperature control module, A thermoelectric element positioned in at least one of the crystal growth module frame, the light emitting module frame, and the detection module frame; and A protein crystal growth monitoring device comprising a heat sink thermally connecting at least one of the crystal growth module frame, the light emitting module frame, and the detection module frame to the device case.

7. In paragraph 1, A protein crystal growth monitoring device, wherein the crystal growth module further includes a diaphragm positioned inside the storage.

8. In paragraph 1, A protein crystal growth monitoring device further comprising an assembly case for accommodating the crystal growth module and the monitoring module.

9. In paragraph 8, A first buffer structure located on one side of the above assembly case; and A protein crystal growth monitoring device further comprising a second buffer structure positioned on the other side of the assembly case.

10. In paragraph 1, A main circuit assembly configured to control the operation of the above protein crystal growth monitoring device; and A protein crystal growth monitoring device comprising a connecting port formed on one surface of the device case for electrically connecting the main circuit assembly to an external device.

Images