Optical signal detection device

Abstract

The present disclosure relates to an optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler. The optical signal detection device comprises: a light source unit including a light source for generating an excitation light; a body portion coupled to the light source unit and having a plurality of passages formed therethrough; and an emission light detector provided at a side of the body portion and detects emission light emitted from the sample. According to the present disclosure, crosstalk of an optical signal generated in a sample is minimized to accurately and quickly detect the optical signal, maintenance and replacement of a beamsplitter are facilitated, and a plurality of lenses and filters may be accurately and easily arranged, fixed, or replaced.

Description

OPTICAL SIGNAL DETECTION DEVICE

[0001] The present disclosure relates to an optical signal detection device for detecting a nucleic acid reaction.

[0002] Polymerase chain reaction (PCR) is the most widely used nucleic acid amplification reaction, and includes the processes of denaturation of double-stranded DNA, annealing of oligonucleotide primers to a DNA template, and repeated cycles of primer extension by DNA polymerase (Mullis et al., U.S. Pat. Nos. 4, 683, 195, 4, 683, 202, and 4, 800, 159; Saiki et al., (1985) Science 230, 1350-1354). The denaturation of the DNA proceeds at about 95 degrees, and the annealing and primer extension proceeds at a temperature lower than 95 degrees, within 55 to 75 degrees.

[0003] A light source emits excitation light to the samples, and a fluorescent material included in the samples excited by the excitation light emits fluorescence. A detector is configured to detect emission light emitted from the fluorescent material to analyze the amplification reaction. In such a fluorescence detection type device, it is necessary to accurately provide excitation light to a sample and accurately provide emission light to a detector.

[0004] The emission light emitted from the sample is guided by a beamsplitter to the detector. The excitation light emitted from the light source passes through the beamsplitter and is provided to the sample, and the emission light emitted from the sample is reflected by the beamsplitter and provided to the detector.

[0005] A nucleic acid analysis system capable of performing nucleic acid analysis on a plurality of samples in real-time is being used in the form of one fluorescence detection module having the above-described configuration. In general, in order to perform nucleic acid analysis on a plurality of samples in real-time, a plurality of light sources and a plurality of filters are provided in one fluorescence detection module. In this case, the plurality of filters used are for detecting a specific wavelength band of the fluorescent material included in the sample.

[0006] However, since the plurality of filters have wavelength bands adjacent to each other, when excitation light is irradiated to a plurality of samples at the same time, crosstalk due to fluorescent signals of adjacent bands is generated, and thus it is difficult to accurately measure experimental results. In consideration of the influence of crosstalk, conventionally, apparatuses have been developed with methods of correcting crosstalk signals software-wise or methods of sequentially exciting and scanning samples such that fluorescent signals in adjacent bands are not simultaneously emitted hardware-wise.

[0007] There is a limitation in increasing the accuracy of the detection signal by correcting the crosstalk signals using a computer, and a method of detecting by sequentially scanning samples one by one in hardware has a disadvantage in that the scan time inevitably increases as the number of samples increases.

[0008] In addition to the crosstalk, there are various other factors that affect the accurate detection of the fluorescence signal emitted from the sample, but the related arts have structures that make it difficult to identify and respond to such factors.

[0009] In order to accurately and rapidly detect an optical signal generated in a sample by using a fluorescence detection device, it is necessary to check whether light is normally irradiated from a light source at a preset timing and whether light is accurately irradiated to a preset region or a sample. In addition, various components (e.g., a lens, a filter, a beamsplitter, etc.) on an optical path must be accurately arranged, and furthermore, whether the detector itself can detect a constant value under the same condition, that is, the reliability of the detector is also important.

[0010] In addition, fine misalignment or breakage of any one of the various components on the optical path, particularly the position of the beamsplitter, may cause failure and malfunction of the optical module. In this case, it takes a lot of time and technical skills to replace or repair the entire optical module.

[0011] In addition, fine misalignment or breakage of any one position of a plurality of lenses or filters may cause failure of the optical module and malfunction or inaccuracy detection results. Even in this case, it is necessary to replace the entire optical module, or a lot of time and technical skills are required to repair it.

[0012] Therefore, there is a need for an optical module that can accurately and rapidly detect an optical signal generated in a sample by minimizing crosstalk using a fluorescence detection device, facilitate maintenance and replacement of a beamsplitter, precisely and easily arrange and fix a plurality of lenses and filters, and facilitate replacement.

[0013] Patent No. KR 2014-0002241 A and Patent No. KR 10-0601964 B1 are examples of prior art.

[0014] In this background, the present disclosure provides an optical signal detection device having a new structural feature capable of accurately and quickly detecting an optical signal generated from a sample.

[0015] In addition, the present disclosure provides an optical signal detection device having a structure capable of preventing crosstalk even when light irradiation is simultaneously performed on a plurality of samples.

[0016] In addition, the present disclosure provides an optical signal detection device formed in a structure that is easy to monitor and respond to factors affecting the signal values detected by a detector.

[0017] In addition, the present disclosure provides an optical signal detection device in which a beamsplitter assembly is formed to be easily attachable to and detachable from a housing of an optical module according to a user's need.

[0018] In addition, the present disclosure provides an optical signal detection device in which a lens-filter unit, in which a lens and a filter are coupled to each other at a predetermined distance, is insertable into or removable from the optical signal detection device.

[0019] In addition, the present disclosure provides an optical signal detection device formed in a structure that has excellent assembly properties and is convenient in maintenance.

[0020] In order to achieve the above object, an aspect of the present disclosure provides an optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device including: a light source unit including a light source for generating an excitation light; a body portion coupled to the light source unit and having a plurality of passages formed therethrough; and an emission light detector provided at one side of the body portion, for detecting an emission light emitted from the sample, wherein a plurality of recesses in which the reaction vessel is disposed are provided below the body portion, wherein a distance between two adjacent recesses is formed to be spaced apart by a first distance, a distance between respective end portions of two adjacent said passages is formed to be spaced apart by a second distance, and the second distance is larger than the first distance.

[0021] Another aspect of the present disclosure provides an optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device including: a light source unit including a light source for generating an excitation light; a housing coupled to the light source unit and having a plurality of passages penetrating therethrough and an inwardly inclining slot cut therein; an emission light detector provided at a side of the housing, for detecting an emission light emitted from the sample; and a beamsplitter assembly including a beamsplitter for each of the passages, wherein the beamsplitter assembly is slidably inserted into and coupled with the slot.

[0022] Yet another aspect of the present disclosure provides an optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device including: a light source for generating an excitation light; a housing having a passage penetrating therethrough; and an emission light detector coupled to one side of the housing, for detecting an emission light emitted from the sample, wherein a lens-filter unit is inserted and installed in the passage, and wherein the lens-filter unit includes: a lens; a mount on which the lens is mounted; and a filter fixed to be spaced apart from the lens by a predetermined distance by the mount

[0023] According to an embodiment of the present disclosure, a plurality of reaction vessels, for example, wells, tubes, or capillaries, are detected while an optical module including a plurality of optical units moves. Thus, time is reduced as compared with a method in which one optical unit scans the entire reaction vessel.

[0024] In addition, even when excitation light is simultaneously irradiated to a sample from a plurality of optical units, a plurality of samples can be rapidly scanned while minimizing crosstalk by a plurality of passages formed penetrating through the housing.

[0025] In addition, the beamsplitter assembly can be easily slid and inserted into or removed from the optical module, and thus a user can easily replace and assemble the beamsplitter as necessary.

[0026] In addition, as the lens and the filter are installed in the optical module while in a state of being coupled to the mount, an error does not occur in the spacing between the lens and the filter, and distortion of light due to distortion between components is prevented, thereby securing stability.

[0027] In addition, the lens-filter unit, in which a lens and a filter are coupled to each other at a predetermined distance, can be easily inserted into or removed from the optical module, and thus a user can easily replace the lens-filter unit, if necessary.

[0028] In addition, it is easy to assemble the housing, through which the plurality of passages are formed, with the other remaining components forming an optical path, thereby improving the manufacturing and productivity of the optical signal detection device.

[0029] In addition, it is easy to assemble the housing, through which the plurality of first passages and second passages are formed, with the remaining components forming an optical path, thereby improving the manufacturing and productivity of the optical signal detection device.

[0030] In addition, when a problem occurs in the light emitting step of a light source by means of the excitation light detector, the cause of the problem can be easily ascertained, and the reliability of the emission light detector can be increased.

[0031] In addition, since emission light may pass through a sample well while intensively transmitting light to an accurately intended sample well by a condensing lens provided for each optical path according to each optical unit, a stable and highly reliable signal may be detected even when the optical module is continuously moving.

[0032] FIG. 1 is a perspective view of an optical module according to an embodiment of the present disclosure.

[0033] FIG. 2 is a conceptual diagram for describing an arrangement of components of an optical signal detection device according to an embodiment of the present disclosure.

[0034] FIG. 3 is a conceptual diagram for describing an arrangement of components of an optical signal detection device according to another embodiment of the present disclosure.

[0035] FIG. 4 is a schematic diagram illustrating an example of the distance between recesses in a reaction portion according to an embodiment of the present disclosure.

[0036] FIG. 5 is a schematic diagram for describing an example of a movement pattern of an optical module according to an embodiment of the present disclosure.

[0037] FIG. 6 is a schematic view illustrating a case where movement proceeds according to the movement pattern illustrated in FIG. 5.

[0038] FIG. 7 is a schematic view illustrating a final movement step in the movement pattern shown in FIG. 6.

[0039] FIG. 8 is a schematic diagram for describing a symmetric feature of an optical module according to an embodiment of the present disclosure.

[0040] FIG. 9 is a schematic view for describing a symmetric feature of an optical module according to another embodiment of the present disclosure.

[0041] FIG. 10 is an exploded perspective view for illustrating an optical module according to an embodiment of the present disclosure.

[0042] FIG. 11 is a side view of an optical module according to an embodiment of the present disclosure.

[0043] FIG. 12 is a cross-sectional view of the optical module taken along line A-A of FIG. 11.

[0044] FIG. 13 is a detailed cross-sectional view of a portion indicated by square B of FIG. 12.

[0045] FIG. 14 is a cross-sectional view separately showing only the housing shown in FIG. 12.

[0046] FIG. 15 is a cross-sectional perspective view of the housing taken along line C-C of FIG. 14.

[0047] FIG. 16 is an exploded perspective view of an excitation lens-filter unit according to an embodiment of the present disclosure.

[0048] FIG. 17 is an exploded perspective view of a beamsplitter assembly according to an embodiment of the present disclosure.

[0049] FIG. 18 is a perspective view illustrating a beamsplitter assembly separated from a body portion according to an embodiment of the present disclosure.

[0050] FIG. 19 is an exploded perspective view of a condensing lens unit according to an embodiment of the present disclosure.

[0051] FIG. 20 is a perspective view illustrating a state in which a frame unit and an excitation light detection unit are coupled to each other according to an embodiment of the present disclosure.

[0052] FIG. 21 is an exploded perspective view illustrating an emission light detection unit and a temperature control unit according to an embodiment of the present disclosure.

[0053] Hereinafter, the present disclosure will be described in detail with reference to an embodiment and exemplary drawings. These embodiments are provided only for more specifically describing the present disclosure, and it will be apparent to those skilled in the art that the scope of the present disclosure is not limited by these embodiments according to the gist of the present disclosure.

[0054] In addition, in adding reference numerals to components of each drawing, it should be noted that the same components are denoted by the same reference numerals as possible even though they are illustrated in different drawings. In addition, in describing the present disclosure, when it is determined that a detailed description of a related known configuration or function may obscure the gist of the present disclosure, the detailed description thereof will be omitted.

[0055] In addition, in describing the components of the present disclosure, terms such as first, second, A, B, (a), (b), (i), (ii), and the like may be used. Such terms are only for distinguishing the components from other components, and the nature, sequence, or order of the corresponding components is not limited by the terms. When a component is described as being "connected", "coupled", or "fastened" to another component, the component may be directly connected or connected to the other component, but it may be understood that another component may be "connected", "coupled", or "fastened" between each component.

[0056] The present disclosure relates to an optical signal detection device that can be used in a detection device for detecting a target analyte in a sample. The optical signal detection device includes: a movable optical module including a light source and a detector; and a reaction portion in which a reaction vessel, in which target analytes are contained, is disposed.

[0057] As used herein, a "sample" may include a biological sample (e.g., cells, tissues, and fluid from a biological source) and a non-biological sample (e.g., food, water, and soil). The biological sample may include viruses, bacteria, tissues, cells, blood (e.g., whole blood, plasma, and serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, feces, ocular fluid, semen, brain extract, spinal fluid, joint fluid, thymus fluid, bronchial lavage fluid, ascites, and amniotic fluid. The sample may also include natural nucleic acid molecules isolated from biological sources and synthetic nucleic acid molecules. According to an embodiment of the present disclosure, the sample may include additional materials such as water, deionized water, saline solution, pH buffer, acidic solution, and alkaline solution.

[0058] A target analyte refers to an analyte that is the subject to analysis. The analysis may mean, for example, obtaining information on the presence, amount(content), concentration, sequence, activity, or properties of an analyte in a sample. Analytes may include a variety of substances (e.g., biological substances and non-biological substances such as compounds). Specifically, the analyte may include biological materials such as nucleic acid molecules (e.g., DNA and RNA), proteins, peptides, carbohydrates, lipids, amino acids, biological compounds, hormones, antibodies, antigens, metabolites, and cells. According to an embodiment of the present disclosure, the analyte may be nucleic acid molecules.

[0059] The optical signal generated in the sample may be, for example, an optical signal that is generated depending on the properties of the target analyte, such as activity, amount, or presence (or absence). The magnitude, change, etc. of the optical signal serves as an indicator that qualitatively or quantitatively indicates the characteristics, specifically the presence or absence, of the target analyte. The target analyte may be, for example, a target nucleic acid sequence or a target nucleic acid molecule including the same. Therefore, the optical signal detection device of the present disclosure may be a target nucleic acid sequence detection device.

[0060] Components of optical module and arrangement thereof

[0061] First, components of an optical module according to an embodiment of the present disclosure and arrangement thereof will be described with reference to FIGS. 1 to 3. FIG. 1 is a perspective view of an optical module according to an embodiment of the present disclosure. The optical module according to an embodiment of the present disclosure includes a light source unit 100, a body portion 200, 200A, and 200B, a frame unit 300, an emission light detection unit 500, and a temperature control unit 600. Each component may be manufactured to be simply assembled and coupled to each other.

[0062] The light source unit 100 includes a light source for generating excitation light, and may include, for example, a plurality of LEDs, a laser, an optical fiber, and other components having functions as a light source, and may be configured to control the same.

[0063] The body portion 200 is coupled to the light source unit 100, and the excitation light generated from the light source unit 100 may pass through the body portion 200. The body portion 200 may be provided below the light source portion 100, and may include “n” number of body portions having the same configuration. As illustrated in FIG. 1, according to an embodiment of the present disclosure, the body portion 200 may include a first body portion 200A and a second body portion 200B. Hereinafter, a repeated description of common detailed components provided in each of the body portions 200, 200A, and 200B will be omitted.

[0064] The arrangement of components of an optical signal detection device according to an embodiment of the present disclosure will be described with reference to FIG. 2. FIG. 2 is a conceptual diagram for describing the arrangement of components of an optical signal detection device according to an embodiment of the present disclosure.

[0065] The optical signal detection device according to an embodiment of the present disclosure may include a control unit 20 that controls overall mechanical operations, an optical module configured to perform light irradiation and detection, and a reaction portion 10 in which a sample is provided. Here, the optical module may include a plurality of optical units, and FIG. 2 is a diagram for describing the arrangement of components and light path in one optical unit. For example, the optical module of the present disclosure may include six optical units.

[0066] The optical unit according to an example embodiment may include a light source 110, an excitation lens-filter unit 220, a beamsplitter 234, a condensing lens unit 240, an emission lens-filter unit 250, and an emission light detector 520. Here, the excitation lens-filter unit 220, the beamsplitter 234, the condensing lens unit 240, and the emission lens-filter unit 250 are components included in the body portion 200, and may be fixed at designated positions. The emission light detector 520 may be included in the emission light detection unit 500 and provided at one side of the body portion 200.

[0067] In FIG. 2, a solid line arrow indicates a path of light where excitation light is irradiated from the light source 110 to a sample provided in the reaction portion 10. Light emitted from the light source 110 may be referred to as excitation light, and a path of the excitation light reaching the sample from the light source 110 may be referred to as an excitation light path. In addition, in FIG. 2, a dashed arrow indicates a path of light where the emission light emitted from the sample provided in the reaction portion 10 reaches the emission light detector 520 and is detected thereby. As such, light emitted from the sample may be referred to as emission light, and a path of light reaching the emission light detector 520 from the sample may be referred to as an emission light path.

[0068] According to an excitation light path indicated by a solid line arrow, light irradiated from the light source 110 passes through the excitation lens-filter unit 220, the beamsplitter 234, and the condensing lens unit 240 to reach the reaction portion 10. According to an emission light path indicated by a dashed arrow, emission light emitted from a sample provided in the reaction portion 10 passes through the condensing lens unit 240, is reflected toward the emission lens-filter unit 250 by the beamsplitter 234, and passes through the emission lens-filter unit 250 to reach the emission light detector 520. The signal detected from the emission light detector 520 may be transmitted back to the control unit 20 to be analyzed.

[0069] Here, the control unit 20 is a unit for controlling the optical signal detection device according to an embodiment of the present disclosure, and may be directly or indirectly connected to the light source 110 and the emission light detector 520 (dotted arrow). For example, the light source 110 and the emission light detector 520 may be connected to a circuit board that controls each detailed operation, and the control unit 20 may include each of the circuit boards. That is, the operations of the light source 110 and the emission light detector 520 may be individually controlled. In an embodiment of the present disclosure, the circuit board of the emission light detector 520 may be a printed circuit board included in the emission light detection unit 500. In addition, the circuit board of the light source 110 may be a light source control board included in the light source unit 100.

[0070] The light source 110 is a device that emits light to excite an optical label included in a sample, and may be a light emitting diode (LED) which includes an organic LED, an inorganic LED, and a quantum dot LED, or a laser unit which includes a tunable laser, a He-Ne laser, and an Ar laser. According to an embodiment of the present disclosure, the light source 110 may be an LED.

[0071] Meanwhile, the light source 110 may be used by way of a "light source-optical fiber" method. In this case, the optical fiber is installed on the light source mount 120 (see FIG. 10), and the light source 110 is installed on another portion of the optical signal detection device to be optically connected to the optical fiber. With respect to "installation in a light source mount," it is contemplated herein that a light source encompasses a light source-optical fiber. That is, the fact that the light source is installed on the light source mount encompasses that the optical fiber connected to the light source is installed on the light source mount.

[0072] The excitation lens-filter unit 220 filters light emitted from the light source 110, that is, the excitation light. The filter may selectively pass light of a specific wavelength region among light emitted from the light source 110, or may not selectively pass light of a specific wavelength region. By selectively passing it is meant passing at least 50%, 60%, 70%, 80%, or 90% of the light of the desired wavelength region. The selective non-passing refers to non-passing and blocking of 50%, 60%, 70%, 80%, or 90% or more of the light amount of the desired wavelength region.

[0073] The excitation lens-filter unit 220 of the present disclosure selectively passes light of a specific wavelength region among light emitted from the light source 110 to irradiate the sample. As a result, only a specific optical label among the optical labels included in the sample generates an optical signal. The optical label may be an optical label selected from the group consisting of FAM, CAL Fluor Red 610, HEX, Quasar 670, and Quasar 705. That is, the excitation wavelength of the excitation light provided by the light source 110 and the excitation lens-filter unit 220 may include, for example, 450-490 nm (for FAM or SYBR Green I), 515-535 nm (for Hex, Vic, Tet or Cal Gold 540), 560-590 nm (for Rox, Texas Red or Cal Red 610), 620-650 nm (for Cy5 or Quasar 670), and 672-684 nm (for Quasar 705).

[0074] The excitation light having passed through the excitation lens unit 220 passes through the condensing lens unit 240 via the beamsplitter 234. The beamsplitter 234 may be a wavelength selective beamsplitter or a dichroic beamsplitter. Accordingly, the beamsplitter 234 may reflect or pass light in a wavelength selective manner.

[0075] The excitation light that has passed through the beamsplitter 234 may be condensed by the condensing lens unit 240 and may reach a sample provided in the reaction portion 10. The condensing efficiency is increased by the condensing lens unit 240, and an optical signal, that is, emission light, may appear more clearly from the optical label included in the sample. The emission light passes through the condensing lens unit 240 again and is reflected toward the emission lens-filter unit 250 by the beamsplitter 234.

[0076] Like the excitation lens-filter unit 220, the emission lens-filter unit 250 selectively passes light of a specific wavelength region among the transmitted light. The emission lens-filter unit 250 selectively passes light of a specific wavelength region among the emission light emitted from the sample so as to be detected by the emission light detector 520. However, it is preferable that the filters used in the emission lens-filter unit 250 and the excitation lens-filter unit 220 in one optical unit pass light of different wavelengths. As described above, the signal detected by the emission light detector 520 after passing through the emission lens-filter unit 250 may be analyzed by the control unit 20.

[0077] Next, the arrangement of components of an optical signal detection device according to another embodiment of the present disclosure will be described with reference to FIG. 3. FIG. 3 is a conceptual diagram for describing an arrangement of components of an optical signal detection device according to another embodiment of the present disclosure.

[0078] As shown in FIG. 3, the optical signal detection device may further include an excitation light detector 420. That is, the optical unit according to another exemplary embodiment of the present disclosure may include a light source 110, an excitation lens-filter unit 220, a beamsplitter 234, an excitation light detector 420, a condensing lens unit 240, an emission lens-filter unit 250, and an emission light detector 520.

[0079] The optical unit shown in FIG. 3 has a similar main configuration compared to that of FIG. 2, except that the excitation light detector 420 is further included , and thus a repeated description thereof will be omitted. Like FIG. 2, a solid line arrow in FIG. 3 indicates an excitation light path, and a dashed arrow indicates an emission light path.

[0080] According to an embodiment of the present disclosure, the excitation light detector 420 may be configured to monitor an operating state of the light source 110. That is, the light output value of the light source 110 may be controlled according to a signal generated from the excitation light detector 420. The excitation light detector 420 may detect a part of the light emitted from the light source 110. The light emitted from the light source 110 may pass through the excitation lens-filter unit 220 and may be partially reflected by the beamsplitter 234 to reach the excitation light detector 420. A part of the excitation light reaching the excitation light detector 420 may be used as a feedback signal in the control unit 20.

[0081] For example, the beamsplitter 234 reflects at least 4% of the excitation light that has passed through the excitation lens-filter unit 220 toward the excitation light detector 420, and passes the rest of the excitation light. That is, 96% of the excitation light may pass through the beamsplitter 234 and the condensing lens unit 240 to be irradiated to the sample provided in the reaction portion 10. The excitation light detector 420 may detect an optical signal by generating an electrical signal according to the intensity of the optical signal.

[0082] The excitation light detector 420 may detect light in a way where the wavelength of light is distinguished to detect the amount of light for each wavelength, or may detect the total amount of light regardless of the wavelength. For example, the excitation light detector 420 may be a photodiode, a photodiode array, a photo multiplier tube (PMT), a CCD image sensor, a CMOS image sensor, an avalanche photodiode (APD), or the like.

[0083] The control unit 20 shown in FIG. 3 may further include a feedback control board, which is a circuit board capable of controlling the excitation light detector 420. The feedback control board may be directly or indirectly connected to the light source control board that controls the light source 110. The control unit 20 may control a light emission operation of the light source 110, and may receive signals from the excitation light detector 420 and the emission light detector 520. Accordingly, the optical module may operate in at least two modes based on the signal for the light source 110 from the excitation light detector 420.

[0084] When the transmitted signal is included in a preset parameter, the optical module may be operated in a “maintaining mode”. In the maintaining mode, the output may be controlled such that the light intensity of the light source 110 is continuously maintained constant. When the transmitted signal is out of the preset parameter, the optical module may be operated in an “error checking mode”.

[0085] In the error checking mode, the movement of the optical module may be stopped. That is, when a problem occurs in the light emission stage of the light source 110 by the excitation light detector 420, the cause of the problem may be easily identified, and the reliability of the emission light detector 520 may be increased.

[0086] In a state in which the movement of the optical module is stopped, the user may recognize that a problem has occurred in at least one component in the light source 110 or a light path from the light source 110 to the excitation light detector 420, and inspection is possible.

[0087] A problem may occur in the light source 110, for example, when the light source 110 is an LED, and the LED may have reached the end of its lifespan, or can no longer emit a certain amount of light. When a problem occurs in the excitation light detector 420, the excitation light detector 420 may be broken or damaged. In addition, the excitation lens-filter unit 220 or the beamsplitter assembly 230 may be misaligned, or some of the detailed components such as lenses or filters may be defective or damaged.

[0088] When there is no problem, as described in FIG. 2, the excitation light that has passed through the beamsplitter 234 may be condensed by the condensing lens unit 240 to reach the sample provided in the reaction portion 10. The emission light passes through the condensing lens unit 240 again and is reflected toward the emission lens-filter unit 250 by the beamsplitter 234. The signal detected by the emission light detector 520 after passing through the emission lens-filter unit 250 may be analyzed by the control unit 20.

[0089] Here, when there is no problem with the signal detected by the excitation light detector 420, but there is a problem with the signal detected by the emission light detector 520, the control unit 20 may determine that there is a problem in the emission lens-filter unit 250 or the emission light detector 520. As the problem occurs, the control unit 20 may notify the user of whether there is a defect according to a predetermined protocol.

[0090] Crosstalk preventing structure

[0091] In an embodiment of the present disclosure, an optical module including an optical unit as described above may move over an entire sample well that is a subject of optical signal detection, to detect an optical signal of a sample. As the plurality of optical units are simultaneously operated, excitation light may be irradiated to the plurality of sample wells, and in this case, a structure of a device for detecting an optical signal according to an embodiment of the present disclosure for preventing crosstalk that may occur, will be described with reference to FIGS. 4 to 7.

[0092] Next, referring to FIGS. 4 to 7, a plurality of recesses R1, R2, R3, . . . , Rnof the reaction portion 10 and a spacing formation feature of a plurality of openings 211a, and an exemplary movement pattern of the optical module according to an embodiment of the present disclosure will be described.

[0093] As shown in FIG. 4, the optical signal detection device according to an embodiment of the present disclosure may include a reaction portion 10 including “n” number of recesses R1, R2, R3, . . . , Rnformed to allow the plurality of reaction vessels to be disposed therein. Here, “n” is an integer equal to or greater than 2. FIG. 4 is a schematic diagram illustrating an example of the distance between the recesses R1, R2, R3, . . . , Rnin a reaction portion 10 according to an embodiment of the present disclosure.

[0094] In an embodiment of the present disclosure, the reaction portion 10 is configured such that reaction vessels in which the sample is accommodated are disposed so that the reaction of the sample may be stably performed. The reaction portion 10 may be, for example, a heat block provided in a thermal cycler. In this case, the recesses R1, R2, R3, . . . , Rnmay be cavities formed in the heat block. One of the recesses R1, R2, R3, . . . , Rnmay be formed to be spaced apart from another adjacent recess by a first distance d1. That is, the “n” number of recesses R1, R2, R3, . . . , Rnmay be arranged to be spaced apart from each other at regular intervals. Reaction vessels in which samples are accommodated may be inserted and disposed in the recesses R1, R2, R3, . . . , Rn.

[0095] An example of a movement pattern of an optical module according to an embodiment of the present disclosure in a case where reaction vessels accommodated by “n” number of recesses R1, R2, R3, . . . , Rnhave the form of a 96-well plate will be described with reference to FIGS. 5 to 7. FIG. 5 is a schematic diagram for describing an example of a movement pattern of an optical module according to an embodiment of the present disclosure, FIG. 6 is a schematic diagram illustrating a case where movement proceeds according to the movement pattern illustrated in FIG. 5, and FIG. 7 is a schematic view illustrating a final movement step in the movement pattern shown in FIG. 6.

[0096] As shown in FIG. 5, any one of the plurality of openings 211a provided in the body portion 200 may be formed to be spaced apart from another adjacent opening by a second distance d2. Here, the second distance d2is greater than the first distance d1.

[0097] The body portion 200 shown in FIGS. 5 to 7 includes six openings 211a. The opening 211a may be formed in the body portion 200 to face the reaction portion 10, and the excitation light generated from the light source 110 may be irradiated to the reaction portion 10 through the opening 211a. Here, a horizontal distance between two adjacent openings 211a and a vertical distance between two adjacent openings 211a may be the same second distance d2. The second distance d2may be a multiple of the first distance d1, and more preferably, the second distance d2may be twice the first distance d1.

[0098] For example, when the reaction vessel takes form of a 96-well plate, the first distance d1, which is a distance between the recesses R1, R2, R3, . . . , Rnof the reaction portion 10, may be a horizontal or vertical distance between two adjacent reaction vessels in the 96-well plate that is 9 mm. In this case, the second distance d2may be a horizontal or vertical distance between two adjacent openings 211a that is 18 mm. Accordingly, even when the excitation light is simultaneously irradiated through the two or more openings 211a, independent light paths that do not interfere with each other may be formed.

[0099] That is, since the distance between adjacent openings 211a is greater than the distance between adjacent recesses R1, R2, R3,…Rn, crosstalk in the sample in the reaction vessels accommodated in adjacent recesses R1, R2, R3,…Rncan be avoided.

[0100] As shown in FIGS. 5 to 7, the body portion 200 may be moved in a predetermined pattern with respect to the reaction vessel in which the sample 30 is accommodated. The body portion 200 may be moved in the X-axis direction and the Y-axis direction as indicated by arrows M1, M2, M3,…M23in the drawing. The number of times of switching of the moving direction may vary depending on the arrangement, number, and shape of the reaction vessel.

[0101] Light irradiation is performed through the plurality of openings 211a, and the movement pattern and speed thereof may be set differently depending on the case. Here, the plurality of openings 211a are portions of the plurality of first passages 211 penetrating through the housing 210 in the first direction (Z-direction) (see FIG. 10) and are formed to face the reaction portion 10. The first passage 211 penetrating through the housing 210 may be optically connected to the light source 110, and the excitation light generated from the light source 110 may be irradiated to the reaction portion 10 through the opening 211a.

[0102] In this case, light irradiation may be simultaneously performed on the plurality of samples 30 through the plurality of openings 211a. The excitation light irradiated from each opening 211a is filtered through different passband filters provided in each first passage 211, and may be irradiated to the sample including a wavelength region of light capable of exciting each specific optical label.

[0103] The optical label may be an optical label selected from a group consisting of FAM, SYBR Green I, HEX, VIC, TET, CAL Gold 540, ROX, Texas Red, CAL Fluor Red 610, Cy5, Quasar 670, and Quasar 705.

[0104] The optical module according to an exemplary embodiment of the present disclosure is movable with respect to the reaction portion 10, and as described above, the optical module moves according to a predetermined movement pattern, but light irradiation may be performed in a state in which the plurality of openings 211a are aligned with different recesses R1, R2, R3, . . . , Rn. That is, light of different wavelengths may be aligned and irradiated to different recesses R1, R2, R3, . . . , Rnthrough the plurality of openings 211a.

[0105] In an exemplary embodiment of the present disclosure, an optical unit of the optical signal detection device may slide over the sample wells at a constant speed, and simultaneously, the light irradiation-light detection operation may be performed. According to an embodiment, the body portion 200 may include six openings 211a. In the light irradiation-light detection operation, when each of the six openings 211a is aligned with the reaction vessel (sample well) in which the sample 30 is accommodated, light irradiation may be simultaneously performed through the six openings 211a, or irradiation may be selectively performed through a part thereof. The position of the reaction vessel in which the sample 30 is accommodated corresponds to the positions of the recesses R1, R2, R3, . . . , Rnof the reaction portion 10.

[0106] In an embodiment of the present disclosure, each of the openings 211a of the body portion 200 may be positioned and formed to be aligned with one light source 110. In this case, in the light source unit 100, all of the six light sources 110 with respect to the 96-well plate may be aligned at least once with respect to each sample 30 to simultaneously emit light or selectively emit light.

[0107] In the movement pattern illustrated in FIG. 3, the body portion 200 moves in the (+)X direction from the left to the right along a movement path M1, moves in the (-)Y direction along a movement path M2, and then moves in the (-)X direction along a movement path M3which is the opposite direction of the movement path M1. In the movement pattern according to another configuration, it may start by moving from right to left in the (-)X direction.

[0108] When the body 200 moves along the movement pattern including the movement paths M1, M2, and M3, excitation light may be simultaneously irradiated through one to six openings 211a. The movement pattern and speed of the body portion 200 may be set differently according to circumstances. In an example, the body portion 200 may perform a light irradiation-light detection operation while sliding over the reaction vessel at a constant speed. In another example, the light irradiation-light detection operation may be performed in a manner in which the body portion 200 is moved and then stopped so that the light source unit 100 emits light. That is, when one to six openings 211a are aligned with one to six reaction vessels, the light source 110 of the light source unit 100 may emit light according to the timing.

[0109] FIG. 5 illustrates a state in which one opening 211a is aligned with one sample 30 and emits light at a point at which the body portion 200 starts to move. Although a plurality of movement paths are illustrated in one drawing, for convenience of description, a state in which excitation light is irradiated through the opening 211a is illustrated only once as a colored circle, and the rest are omitted.

[0110] FIG. 6 is a schematic view illustrating a case in which movement is performed according to the movement pattern illustrated in FIG. 5, and illustrates a state in which each of the six openings 211a is aligned with the sample 30 and excitation light is irradiated. When the body portion 200 moves along the movement path M9and moves along the movement path M10, three openings 211a may be aligned with three samples 30.

[0111] FIG. 7 is a schematic diagram illustrating a final movement step in the movement pattern shown in FIG. 6, in which one opening 211a is aligned with one sample 30 with respect to the last remaining sample 30 along the movement path M23of the body portion 200, and excitation light is irradiated. According to FIGS. 5 to 7, the body portion 200 may perform light irradiation on the sample(s) 30 accommodated in the 96-well plate through the six openings 211a through twenty-three horizontal and vertical movements.

[0112] Symmetric optical module

[0113] Symmetric features of an optical module according to embodiments of the present disclosure will be described with reference to FIGS. 8 and 9. FIG. 8 is a schematic diagram for describing a symmetric feature of an optical module according to an embodiment of the present disclosure. FIG. 9 is a schematic view for describing a symmetric feature of an optical module according to another embodiment of the present disclosure.

[0114] As illustrated in FIG. 8, the optical module according to an embodiment of the present disclosure includes a first body portion 200A and a second body portion 200B. The first body portion 200A and the second body portion 200B include the same components therein and are symmetrical with respect to the reference line Ls.

[0115] That is, a light source 110, an excitation lens 221, an excitation filter 223, a beamsplitter 234, an emission filter 252, an emission lens 251, an emission light detector 520, and a condensing lens 241, which are disposed and fixed to the first body portion 200A, are provided in the second body portion 200B in a form symmetrical with respect to the reference line Ls. In an embodiment of the present disclosure, the light source 110 may be an LED, and the emission light detector 520 may be a photodiode.

[0116] In addition, an opening 211a may be formed on the same vertical line as the light source 110 in the lower portion of the first body portion 200A and the second body portion 200B. Here, the excitation lens 221, the excitation filter 223, and the condensing lens 241 are also provided on the same vertical line as the light source 110 and the opening 211a. The excitation light irradiated from the light source 110 and the emission light emitted from the sample may pass through the opening 211a, and the condensing efficiency is increased by the condensing lens 241 provided on the same vertical line, thereby improving the efficiency of the sample detection signal up to 1.5 times.

[0117] The sample may be accommodated in a reaction vessel provided in the recesses R1, R2, R3of the reaction portion 10. The reaction portion 10 may be, for example, a heat block provided in a thermal cycler, and the recesses R1, R2and R3may be cavities formed in the heat block. The reaction vessel can be, for example, a sample well of a 96-well plate. The recesses R1, R2and R3may be formed to be evenly spaced apart by a first distance d1, and the distance between the light source 110 and / or the opening 211a may be formed to be evenly spaced apart by a second distance d2. In this case, the second distance d2is larger than the first distance d1, and preferably, the second distance d2is twice the first distance d1.

[0118] FIG. 8 illustrates a case where the first body portion 200A and the second body portion 200B are aligned so that a recess is located on a vertical line of the light source 110 and / or the opening 211a. Accordingly, when the light sources 110 respectively disposed on the first body portion 200A and the second body portion 200B emit light at the same time, light irradiation and detection are performed only at the positions of the first recess R1and the third recess R3which are provided and aligned on the vertical line. Since light irradiation and detection are not performed on the second recess R2positioned between the first recess R1and the third recess R3, mutual interference between wavelengths of excitation light can be minimized even when the two light sources 110 emit light at the same time.

[0119] Although a pair of optical units is illustrated in FIG. 8, the optical module according to an embodiment of the present disclosure may include three pairs of optical units having the same configuration, which are arranged in the Y-direction. That is, in an exemplary embodiment of the present disclosure, the optical module may include a total of six light sources 110, the openings 211a are designated for each of the light sources 110, and the six openings 211a may be formed in the first body portion 200A and the second body portion 200B to form a 3X2 matrix.

[0120] Although one light source 110 is provided for each optical unit in the exemplary embodiment of the present disclosure, in another exemplary embodiment, excitation light passing through the plurality of openings 211a may be generated by one light source 110, and in still another exemplary embodiment, an optical fiber or an optical guide may be provided for each optical unit to transmit the excitation light to the plurality of openings 211a.

[0121] Hereinafter, a symmetrical feature of an optical module according to still another embodiment of the present disclosure will be described with reference to FIG. 9. The optical unit shown in FIG. 9 has a similar main configuration except that it further includes a feedback control board 410 and an excitation light detector 420 compared to the configuration of FIG. 8, and thus a repeated description thereof will be omitted.

[0122] As shown in FIG. 9, a feedback control board 410 and an excitation light detector 420 are provided between a first body portion 200A and a second body portion 200B which are symmetrical to each other with respect to a reference line Ls. In more detail, the excitation light detectors 420 disposed on the first body portion 200A and the second body portion 200B may be provided at both sides of the feedback control board 410. Here, the excitation light detector 420 and the feedback control board 410 have the same configurations as those described above with reference to FIG. 3, and repeated descriptions thereof will be omitted.

[0123] The feedback control board 410 may be a printed circuit board (PCB) on which excitation light detectors 420 are mounted on both sides thereof, and may be configured to be connected to the light source control board 130. The feedback control board 410 may transmit a signal detected by the excitation light detector 420 to the light source control board 130. The light source control board 130 may control the output of the light source 110 based on the received signal such that the light intensity is continuously maintained constant (maintaining mode). Accordingly, since the sample may be excited with a constant light intensity, reliability of emission light detected from the sample may be improved. When it is determined that there is a problem in the signal transmitted from the feedback control board 410 to the light source control board 130, the movement of the optical module may be stopped, so that the light irradiation and detection operations may be stopped (error checking mode).

[0124] As in FIG. 8, FIG. 9 also shows a pair of optical units, but the optical module may include two or more pairs, preferably three pairs of optical units having the same configuration arranged in the Y-direction. That is, in an embodiment of the present disclosure, the optical module may include a total of six light sources 110, wherein the openings 211a are designated for each of the light sources 110, and the six openings 211a may be formed in the first body portion 200A and the second body portion 200B to form a 3X2 matrix. In this case, three excitation light detectors 420 may be mounted at both sides of the feedback control board 410. That is, a total of six excitation light detectors may be mounted.

[0125] Detailed configuration of an optical module

[0126] A detailed configuration of an optical module according to an embodiment of the present disclosure will be described with reference to FIG. 10. FIG. 10 is an exploded perspective view for illustrating an optical module according to an embodiment of the present disclosure.

[0127] As shown in FIG. 10, the light source unit 100 includes a plurality of light sources 110, a light source mount 120 on which the light sources 110 are mounted, and a light source control board 130 for controlling the light sources 110. The light sources 110 may be coupled and fixed to the light source mount 120, and the light source mount 120 may be coupled and fixed to the light source control board 130.

[0128] The light source 110 is a device that emits light to excite an optical label included in a sample, and may be a light emitting diode (LED) which includes an organic LED, an inorganic LED, and a quantum dot LED, or a laser unit which includes a tunable laser, a He-Ne laser, and an Ar laser. According to an embodiment of the present disclosure, the light source 110 may be an LED.

[0129] The light source mount 120 may stably support and protect the light source 110 and may be firmly fixed to the light source control board 130. When a plurality of light sources 110 are provided in the light source mount 120, a plurality of light source support holes capable of accommodating and supporting the respective light sources 110 are formed. The plurality of light source support holes may be manufactured to be spaced apart from each other by a predetermined distance, and the plurality of light sources 110 may be disposed to be spaced apart from each other by the predetermined distance. The excitation light generated by the plurality of light sources 110 may pass through the first passage 211 formed through the housing 210 in the first direction to reach the reaction portion 10. An opening 211a facing the reaction portion 10 may be formed at one end portion of the first passage 211. The other end portion of the first passage 211 may be optically connected to the light source 110.

[0130] The light source control board 130 is a control unit capable of substantially controlling light emission of the light source 110, and may be a circuit board. That is, the light source control board 130 may be a printed circuit board (PCB) on which the light source 110 such as an LED is mounted by the light source mount 120. The light source control board 130 may receive a signal from the excitation light detection unit 400, and the light emission intensity of the light source 110 may be controlled based on the received signal. The light source mount 120 may be coupled to the light source control board 130 by a coupling means such as a fixing hook. In an exemplary embodiment of the present disclosure, the light source mount 120 is provided for durability and accurate arrangement and assembly of the light source 110, but a configuration of the light source unit 100 is not limited thereto.

[0131] According to an embodiment of the present disclosure, the light source control board 130 may be configured to control the plurality of light sources 110. Here, the light source control board 130 may receive a signal from the excitation light detection unit 400 with respect to each of the light sources 110. The excitation light detection unit 400 may include a plurality of excitation light detectors 420, and each excitation light detector 420 may be configured to monitor an operating state of a designated light source 110. That is, the light output value of each designated light source 110 may be controlled according to the signals generated from the plurality of excitation light detectors 420.

[0132] In an exemplary embodiment of the present disclosure, the light source control board 130 may receive a signal from each excitation light detector 420 for each light source 110, and the light source unit 100 may operate in at least two modes (maintaining mode and error checking mode) according to the received signal.

[0133] The body portion 200 may include a first body portion 200A and a second body portion 200B that are symmetrical to each other, and in another embodiment of the present disclosure, the body portion 200 may be configured to include only one of the first body portion 200A and the second body portion 200B. The body portion 200 may be understood as a component including the housing 210 through which the first passage 211 is formed as well as all the components provided inside the housing 210. That is, the body portion 200 may be understood as a configuration including the housing 210, the excitation lens-filter unit 220, the beamsplitter assembly 230, the condensing lens unit 240, and the emission lens-filter unit 250.

[0134] Here, the first body portion 200A and the second body portion 200B may include a first housing 210A and a second housing 210B, respectively. The first housing 210A and the second housing 210B may be formed in a symmetrical shape that can be separated from each other. The excitation lens-filter unit 220, the beamsplitter assembly 230, the condensing lens unit 240, and the emission lens-filter unit 250 may be accommodated in each of the first and second housings 210A and 210B.

[0135] The size, shape, and number of configurations of the body portion 200 of the present disclosure may be determined according to the number of detection channels. In an embodiment of the present disclosure, one detection channel may be provided for each optical unit. The detection channels may have a maximum detection wavelength of 500-800 nm (specifically, 520-730 nm). For example, the channels can have a maximum detection wavelength of 530 nm, 560 nm, 580 nm, 610 nm, 640 nm, 670 nm or 710 nm. The detection channel may be defined by using the emission filter 252 such that emission light of a specific wavelength reaches the emission light detector 520. The maximum detection wavelength of the detection channel may be determined according to the maximum radiation wavelength of a fluorescent dye, and when the two wavelengths are different from each other, the difference may be in a range of ±10 nm.

[0136] For example, when a total of three detection channels are provided, the optical module of the present disclosure may include three optical units, and the body portion 200 may include one housing 210, three excitation filters 223, three beamsplitters 234, three emission filters 252, and three condensing lenses 241. In this case, three first passages 211 accommodating the excitation filter 223 and three second passages 213 accommodating the emission filter 252 may be formed in the housing 210. That is, a first passage 211, a second passage 213, an excitation filter 223, a beamsplitter 234, an emission filter 252, and a condensing lens 241 may be provided for each detection channel.

[0137] In another example, when a total of six detection channels are provided, the optical module of the present disclosure may include six optical units and two body portions 200A and 200B. In this case, a first body portion 200A and a second body portion 200B may be provided under one light source unit 100. Here, the first body portion 200A may be configured to form three light paths with respect to three light sources 110, and the second body portion 200B may be configured to form three light paths with respect to the remaining three light sources 110. In this case, the first housing 210A of the first body portion 200A and the second housing 210B of the second body portion 200B may have symmetrical shapes that are separable from each other. The first housing 210A and the second housing 210B may be connected by the frame unit 300.

[0138] The frame unit 300 includes a support 310 and a lower frame 320 connected to the support 310. The support 310 may be fixed to a side of the body portion 200, and the lower frame 320 may be fixed to a lower portion of the body portion 200. More specifically, in an embodiment of the present disclosure, the support 310 may be coupled to opposing side surfaces of the first housing 210A and the second housing 210B, and may be coupled to lower portions of the first housing 210A and the second housing 210B.

[0139] The support 310 may protrude upward from the lower frame 320, and may be manufactured integrally with the lower frame 320. The lower frame 320 may support at least a portion of a lower side of the body portion 200. A plurality of bottom holes 321 may be formed in the lower frame 320 so that light emitted from the light source 110 may pass through the lower frame 320. The number of bottom holes 321 may be formed to be equal to the number of the light sources 110 and / or the openings 211a, and may be formed to be positioned on the same vertical line as the plurality of light sources 110 and / or the openings 211a. The openings 211a are formed by the first passages 211, and are formed to be equal to the number of the first passages 211.

[0140] The excitation light detection unit 400 may be fixed to the support 310 protruding upward from the lower frame 320. That is, the excitation light detection unit 400 may be located at one side of the body portion(s) 200, 200A, and / or 200B. The excitation light detection unit 400 is configured to monitor an operating state of the light source 110, and includes a feedback control board 410 and an excitation light detector 420. The feedback control board 410 may be a circuit board capable of substantially controlling the excitation light detector 420. That is, the feedback control board 410 may be a printed circuit board (PCB) on which the excitation light detector 420 is mounted.

[0141] The excitation light detector 420 may detect a part of light emitted from the light source 110. Light may be emitted from the light source 110, and a portion of the light may be reflected by the beamsplitter assembly 230 to reach the excitation light detector 420. In this case, the excitation light detector 420 may detect an optical signal by generating an electrical signal according to the intensity of the optical signal.

[0142] The excitation light detector 420 may distinguish the wavelength of light to detect the amount of light for each wavelength, or may detect the total amount of light regardless of the wavelength. For example, the excitation light detector 420 may be a photodiode, a photodiode array, a photo multiplier tube (PMT), a CCD image sensor, a CMOS image sensor, an avalanche photodiode (APD), or the like.

[0143] An emission light detection unit 500 may be provided at an opposite side of the excitation light detection unit 400. That is, the excitation light detection unit 400 may be located at one side of the body portion(s) 200, 200A, and / or 200B, and the emission light detection unit 500 may be located at the other side thereof. The emission light detection unit 500 includes a printed circuit board 510 and an emission light detector 520. The printed circuit board 510 may be a printed circuit board (PCB) on which the emission light detector 520 is mounted.

[0144] The emission light detector 520 is formed to detect emission light emitted from an optical label included in the sample. Similar to the excitation light detector 420, the emission light detector 520 may detect an optical signal by generating an electrical signal according to the intensity of the optical signal. In addition, the emission light detector 520 may also detect the amount of light for each wavelength by distinguishing the wavelength of the light, or may detect the total amount of light regardless of the wavelength. For example, the emission light detector 520 may also be a photodiode, a photodiode array, a photo multiplier tube (PMT), a CCD image sensor, a CMOS image sensor, an avalanche photodiode (APD), or the like.

[0145] The printed circuit board 510 may be additionally provided with a temperature control unit 600. The temperature control unit 600 is configured to control the temperature of the emission light detector 520. The temperature control unit 600 includes a heat sink 610 and a thermoelectric element 620. Here, the thermoelectric element 620 may be a heating / cooling element such as a Peltier element, which may be controlled by an electrically coupled thermal control circuit. Since the temperature of the emission light detector 520 is kept constant by the temperature adjusting unit 600, the influence of the temperature may be minimized to increase the reliability of the emission light detector 520.

[0146] Internal structure of an optical module and form of a housing

[0147] Next, the internal structure of the optical module and the form of a housing according to an embodiment of the present disclosure will be described with reference to FIGS. 11 to 15. FIG. 11 is a side view of an optical module according to an embodiment of the present disclosure, and FIG. 12 is a cross-sectional view of the optical module taken along line A-A of FIG. 11. FIG. 13 is a detailed view of a portion indicated by square B of FIG. 12. FIG. 14 is a cross-sectional view separately showing only the housing shown in FIG. 12. FIG. 15 is a cross-sectional perspective view of the housing taken along line C-C of FIG. 14.

[0148] As shown in FIG. 11, the light source unit 100 is provided on upper portion of the body portion 200, and the frame unit 300 is provided at a lower portion thereof. The emission light detection unit 500 and the temperature adjusting unit 600 are provided at one side of the body portion 200, and referring to FIG. 12, which is a cross-sectional view taken along line A-A of FIG. 11, the excitation light detection unit 400 is provided at the other side of the body portion(s) 200, 200A, and / or 200B. As shown in FIG. 12, the excitation light detection unit 400 may be provided between the first body portion 200A and the second body portion 200B.

[0149] The coupling relationship among the light source unit 100, the body portion 200, the frame unit 300, the excitation light detection unit 400, the emission light detection unit 500, and the temperature control unit 600 will be described in more detail with reference to FIGS. 13 and 14. The body portion 200 according to an embodiment of the present disclosure may include a housing 210, an excitation lens-filter unit 220, a beamsplitter assembly 230, an emission lens-filter unit 230, and a condensing lens unit 240.

[0150] The housing 210 may include a first passage 211 accommodating the excitation lens-filter unit 220, a slot 212 (see FIG. 14) accommodating the beamsplitter assembly 230, and a second passage 213 accommodating the emission lens-filter unit 230.

[0151] As illustrated in FIG. 14, the first passage 211 and the second passage 213 may be formed to penetrate the housing 210, and the slot 212 may communicate with the first passage 211 and the second passage 213 and may be cut to be inclined toward the inside of the housing 210.

[0152] The first passage 211 and the second passage 213 may penetrate the housing 210 in the first direction and the second direction, respectively. In an exemplary embodiment of the present disclosure, the first direction and the second direction may be perpendicular to each other, and each of the first passages 211 may be formed to match and intersect the second passages 213. In an embodiment of the present disclosure, the first direction and the second direction may be a Z-direction and an X-direction, respectively. Openings 211a and 213a may be formed at an end portion of each of the first passage 211 and the second passage 213. Through each of the openings 211a and 213a, light may pass through towards components coupled to the lower and side surfaces of the housing 210.

[0153] The slot 212 may be cut to be inclined inward in the housing 210 and extend in a third direction to communicate with the plurality of first passages 211 and the plurality of second passages 213. Here, the third direction may be a direction perpendicular to a plane including the first direction and the second direction. In an embodiment of the present disclosure, the third direction may be the Y-direction.

[0154] The first passage 211 may be provided with a first designated position to which the excitation lens-filter unit 220 is fixed. The excitation lens-filter unit 220 filters light emitted from the light source 110. The second passage 213 may be provided with a second designated position to which the emission lens-filter unit 250 is fixed. The emission lens-filter unit 250 filters light emitted from the sample.

[0155] The first designated position and the second designated position may be determined by the first stepped part 211b and the second stepped part 213b, which are stepped parts protruding into the first passage 211 and the second passage 213, respectively. That is, the excitation lens-filter unit 220 and the emission lens-filter unit 250 may be seated by being caught by the first stepped part 211b and the second stepped part 213b protruding into the first passage 211 and the second passage 213, respectively.

[0156] In addition, a first through-hole 211c and a second through-hole 213c may be formed through side surfaces of the first passage 211 and the second passage 213, respectively, and the first fixing portion 214 and the second fixing unit 215 may be inserted through the through-holes to fix the excitation lens-filter unit 220 and the emission lens-filter unit 250, respectively.

[0157] As illustrated in FIG. 13, the light source 110 of the light source unit 100 may be fixed to the light source control board 130 by the light source mount 120, and may be inserted into and accommodated in an end portion of the first passage 211. A plurality of light sources 110 may be provided, and one first passage 211 may be formed per each light source 110.

[0158] The beamsplitter assembly 230 may be provided between the excitation lens-filter unit 220 and the emission lens-filter unit 250. In particular, the beamsplitter 234 provided in the beamsplitter assembly 230 may be disposed in a space where the first passage 211 and the second passage 213 intersect.

[0159] Some of the excited light may be reflected by the beamsplitter 234 and detected by the excited light detector 420 provided in the feedback control board 410. In addition, the emission light emitted from the sample by the beamsplitter 234 may be reflected and detected by the emission light detector 520 provided on the printed circuit board 510.

[0160] A lower portion of the feedback control board 410 may be supported by the lower frame 320. The lower frame 320 may include bottom portions extending to both sides of the feedback control board 410, and a bottom hole 321 may be formed in a portion of the bottom portion. At this time, the bottom hole 321 may be positioned on the same line as the condensing lens 241 formed in the condensing lens unit 240 and the opening 211a formed in the housing 210. That is, the excitation light generated by the light source 110 may pass through all of the opening 211a, the condensing lens 241, and the bottom hole 321 through the first passage 211 to reach the sample 30.

[0161] More specifically, the opening 211a formed in the housing 210 is formed to be smaller than the condensing lens 241, and a stepped part is formed in the lower surface of the housing 210, so that the condensing lens 241 may be seated on the stepped part. At this time, the condensing lens 241 may be maintained in a state of being seated on the lower surface of the housing 210 by the lens holder 242. That is, the condensing lens 241 may be sandwiched and fixed between the lower side surface of the housing 210 and the lens holder 242.

[0162] The shape of the lens holder 242 may be formed to engage with the shape of the lower side of the housing 210. In addition, in a state in which the lens holder 242 is coupled to the lower surface of the housing 210, a portion of the lower frame 320 of the frame unit 300 may be formed to be engaged with the lens holder 242 and the housing 210. That is, the lens holder 242 may be formed so that both sides thereof are engaged between the lower side surface of the housing 210 and the lower frame 320.

[0163] The emission light emitted from the sample 30 may also pass through the bottom hole 321, the condensing lens 241, and the opening 211a combined as described above, and may be reflected by the beamsplitter 234, and then may pass through the emission lens-filter unit 250, and may reach the emission light detector 520 near the heat sink 610 and the thermoelectric element 620.

[0164] Additionally, the shape of the housing 210 will be described in more detail with reference to FIG. 15. As illustrated in FIG. 15, three first passages 211-1, 211-2, and 211-3 may be formed side by side in the housing 210. Each of the first passages 211-1, 211-2, and 211-3 includes a first opening 211a-1, 211a-2, and 211a-3 opened downward.

[0165] In addition, the three second passages 213-1, 213-2, and 213-3 intersecting the respective first passages 211-1, 211-2, and 211-3 may be formed in the X-direction. The slot 212 may be formed in the Y-direction to communicate with an intersection space between the first passages 211-1, 211-2, and 211-3 and the second passages 213-1, 213-2, and 213-3. Although only one housing 210 is illustrated in FIG. 15, the optical module according to an embodiment of the present disclosure may further include a housing having a shape symmetrical to the housing 210 illustrated in FIG. 15.

[0166] Lens-filter unit

[0167] Next, a lens-filter unit according to an embodiment of the present disclosure will be described. The lens-filter unit includes an excitation lens-filter unit 220 and an emission lens-filter unit 250, which are inserted into the first passage 211 and the second passage 213, respectively. For convenience of description, the excitation lens-filter unit 220 among the lens-filter units having the same structure will be mainly described. The excitation lens-filter unit 220 of the optical signal detection device according to an embodiment of the present disclosure will be described in detail with reference to FIG. 16. FIG. 16 is an exploded perspective view of an excitation lens-filter unit 220 according to an embodiment of the present disclosure.

[0168] As illustrated in FIG. 16, the excitation lens-filter unit 220 includes an excitation lens 221, a mount 222, and an excitation filter 223. In this case, the excitation lens 221 may be a convex lens and may be mounted on the mount 222. The excitation filter 223 may be fixed to be spaced apart from the lens 221 by a predetermined distance by the mount 222.

[0169] In particular, describing the structure of the mount 222 in more detail, the mount 222 includes a gripping portion 222a for gripping the excitation lens 221, a filter coupling portion 222c for fixing the excitation filter 223, and a barrel-shaped barrel portion 222b formed between the gripping portion 222a and the filter coupling portion 222c.

[0170] The gripping portion 222a according to an embodiment of the disclosure may include a portion surrounding the side surface of the excitation lens 221 and connected to the barrel portion 222b, and a plurality of fingers formed to surround an edge portion of the excitation lens 221. The gripping portion 222a illustrated in FIG. 16 is illustrated as including three fingers, but in another embodiment, three or more fingers such as four, five, six, and the like may be provided. The gripping portion 222a grips the excitation lens 221 so as to keep it from being separated from the mount 222.

[0171] The excitation lens 221 may serve to collect light emitted from the light source 110. It is preferable that the convex surface of the excitation lens 221 is fixed toward the outside of the mount 222. In this case, the gripping portion 222a or the entire mount 222 may be formed of a flexible material. The flexible material may be, for example, a plastic material, or a moldable crystalline resin such as a polyetheretherketone (PEEK) polymer. As the excitation lens-filter unit 220 is inserted into the first passage 211, the plurality of fingers may be pressed toward the excitation lens 221, thereby more firmly fixing the excitation lens 221. That is, as the plurality of fingers are pressed and tightened by the inner surface of the first passage 211, the excitation lens 221 may be more firmly fixed by the gripping portion 222a.

[0172] The barrel portion 222b may keep the excitation lens 221 and the excitation filter 223 spaced apart by a predetermined distance. More specifically, the excitation lens 221 and the excitation filter 223 may be spaced apart from each other by a stepped part formed at two ends of the barrel portion 222b. In this case, the diameters of the excitation lens 221 and the excitation filter 223 may be larger than the inner diameter of the barrel portion 222b and thus may be seated on stepped parts formed at two ends of the barrel portion 222b. As described above, since the distance between the excitation lens 221 and the excitation filter 223 may be stably maintained, distortion or positional deviation due to repeated use may be prevented.

[0173] A fixing groove recessed to a predetermined depth may be formed at the outer circumference of the barrel portion 222b. In this case, the fixing groove may be recessed along the entire outer circumference of the barrel portion 222b, and in another embodiment, only a part of the outer circumference of the barrel portion 222b may be recessed. At least a portion of the first fixing portion 214 may be accommodated in the fixing groove. The first fixing portion 214 may be inserted into a first through-hole 211c penetrating through a portion of the first passage 211 and accommodated in a fixing groove, thereby fixing the position of the excitation lens-filter unit 220.

[0174] According to an embodiment of the present disclosure, as shown in FIG. 16, when the fixing groove is formed along the outer circumference of the barrel portion 222b, stepped parts may be formed at each of the upper end and the lower end. The first fixing portion 214 may be caught by an upper end or lower end stepped part formed outside the barrel portion 222b by the fixing groove, thereby preventing the barrel portion 222b from moving up and down. In this case, the first fixing portion 214 may be a screw-type component, and is fastened through the first through-hole 211c to be accommodated in at least a portion of the fixing groove.

[0175] According to an exemplary embodiment of the present disclosure, the excitation filter 223 may be fixed to the filter coupling portion 222c forming the lower end of the mount 222. The filter coupling portion 222c may be formed to surround at least a portion of an outer diameter of the excitation filter 223. In this case, a gap 222d may be formed in a portion of the circumference of the filter coupling portion 222c. An adhesive may be injected into the side surface of the excitation filter 223 through the gap 222d. In an example, the adhesive may be a bonding liquid that can be cured with UV light. Since the adhesive may be injected through the gap 222d, the adhesive may be applied to the side surface of the excitation filter 223, not the surface thereof, and accordingly, a gap error due to the thickness of the adhesive does not occur. That is, a distance between the excitation lens 221 and the excitation filter 223 may be accurately maintained.

[0176] In addition, since the excitation lens 221 and the excitation filter 223 are coupled to the mount 222 as described above, the lens and / or the filter may be conveniently replaced. A first stepped part 211b (see FIG. 14) may be formed inside the first passage 211 of the housing 210, and as one end of the mount 222 is caught by the first stepped part 211b, the excitation lens-filter unit 220 may be seated on the first passage 211. As shown in FIG. 13, in the excitation lens-filter unit 220, the filter coupling portion 222c may be seated in the first passage 211, and in the emission lens-filter unit 250, the gripping portion 222a may be seated in the second passage 213.

[0177] The aforementioned filter for filtering the excitation light may be the excitation filter 223 included in the excitation lens-filter unit 220 of the present disclosure. The excitation filter 223 selectively passes light of a specific wavelength region among light emitted from the light source 110 to irradiate the sample. As a result, only a specific optical label among the optical labels included in the sample generates an optical signal. The optical signal detection device according to the present disclosure may include a plurality of light sources 110, and one excitation lens-filter unit 220 may be provided for each of the light sources 110. In this case, each of the excitation lens-filter units 220 may include a filter that passes light in a wavelength region capable of exciting at least one of the optical labels.

[0178] In an embodiment of the present disclosure, the filter may be a bandpass filter. The bandpass filter refers to a filter that selectively transmits light in a certain wavelength region. A wavelength region of light transmitted through the bandpass filter is referred to as a passband of the filter. A filter including a specific passband means a filter that passes light of a wavelength included in the specific passband.

[0179] As an example, the plurality of excitation lens-filter units 220 may include an excitation lens-filter unit including a filter of a first pass band, and an excitation lens-filter unit including a filter of a second pass band. Each of the first pass band and the second pass band may include a wavelength region of light capable of exciting a specific optical label. The optical label may be an optical label selected from a group consisting of FAM, SYBR Green I, HEX, VIC, TET, CAL Gold 540, ROX, Texas Red, CAL Fluor Red 610, Cy5, Quasar 670, and Quasar 705. Each of the plurality of excitation lens-filter units 220 may pass excitation light capable of exciting different optical labels.

[0180] The emission lens-filter unit 250 may be manufactured to have the same structure as that of the excitation lens-filter unit 220. The emission lens-filter unit 250 may be different from the excitation lens-filter unit 220 in some filter types and sizes, but main configurations such as a lens, a mount, a filter, a fixing unit, and the like are the same, and thus a repeated description thereof will be omitted. However, the excitation lens-filter unit 220 and the emission lens-filter unit 250 may include filters of different passbands.

[0181] Beamsplitter assembly

[0182] Hereinafter, the beamsplitter assembly 230 of the optical signal detection device according to an example embodiment will be described in more detail with reference to FIGS. 17 and 18. FIG. 17 is an exploded perspective view of the beamsplitter assembly 230 according to an embodiment of the present disclosure, and FIG. 18 is a perspective view illustrating a beamsplitter assembly 230 separated from the housing 210 of a body portion 200, 200A, and / or 200B according to an embodiment of the present disclosure.

[0183] As illustrated in FIG. 17, the beamsplitter assembly 230 may include a first bracket 231 and a second bracket 235 on which a plurality of beamsplitters 234 may be mounted. In this case, the beamsplitters 234 may be spaced apart from each other by a predetermined distance between the first bracket 231 and the second bracket 235 to be positioned and fixed.

[0184] In an embodiment of the present disclosure, the beamsplitter 234 may be a dichroic beamsplitter or a multi-dichroic beamsplitter. The beamsplitter 234 may be seated on the second bracket 235, and the first bracket 231 may be closely coupled to the second bracket 235 by a coupling member 233. That is, the beamsplitter 234 may be sandwiched and fixed between the first bracket 231 and the second bracket 235.

[0185] In this case, an opening may be formed in each of the first bracket 231 and the second bracket 235 at a position corresponding to the beamsplitter 234 so that light from the light source 110 and / or the sample 30 may partially pass through and / or be reflected by the beamsplitter 234. In an embodiment of the present disclosure, each beamsplitter 234 may have a passband that selectively passes each excitation light wavelength region. That is, the excitation lens-filter unit 220 according to the present disclosure may have a passband that selectively passes the passband of the filter 223. In addition, each beamsplitter 234 may further have a passband that reflects light in the wavelength region of the emission light emitted from the sample 30.

[0186] In addition, the first bracket 231 may include an upper guide 232 formed to partially protrude from the first bracket 231. The second bracket 235 may also be provided with a lower guide 236 formed to partially protrude from the second bracket 235. The upper guide 232 may be formed on a surface opposite to a surface on which the first bracket 231 contacts the beamsplitter 234, and may be formed in a shape corresponding to a groove formed in the slot 212. Similarly, the lower guide 236 may be formed on a surface opposite to a surface on which the second bracket 235 contacts the beamsplitter 234, and may be formed in a shape corresponding to a groove formed in the slot 212. In an embodiment, the degree of protrusion of the upper guide 232 and the degree of protrusion of the lower guide 236 may be different from each other, and accordingly, the assemblability of the beamsplitter assembly 230 may be improved, and the beamsplitter assembly may be prevented from being inserted in opposite directions. In addition, the beamsplitter assembly 230 may be positioned at a correct position of the slot 212 and may be prevented from being distorted.

[0187] In addition, in an embodiment of the present disclosure, the upper guide 232 and the lower guide 236 may be selectively provided. For example, when the plurality of beamsplitters 234 are provided to correspond to the plurality of first passages 211, the plurality of upper and lower guides 232 and 236 may be formed on both sides of each beamsplitter 234. Accordingly, the plurality of beamsplitters 234 may be independent from each other, and thus optical paths thereof may not overlap each other, and interference of unintended light from the adjacent first passages 211 may be prevented. Also, the plurality of beamsplitters 234 may be dichroic beamsplitters having different passbands. That is, they may be beamsplitters that reflect and / or pass light of different wavelengths.

[0188] In addition, a stopper 237 may be further formed on the second bracket 235. The stopper 237 determines the position of the beamsplitter assembly 230 such that the beamsplitter 234 is accurately disposed in a space intersecting the first passage 211 and the second passage 213. For example, when the beamsplitter assembly 230 is inserted into the housing 210, the stopper 237 may be caught by a portion of the surface of the housing 210 so as not to be inserted more than a predetermined distance.

[0189] The stopper 237 may be a protrusion formed by extending an upper edge of the beamsplitter assembly 230 in the direction of one side or both sides of the upper edge. As illustrated in FIG. 17, the stopper 237 may be a protrusion formed perpendicular to the second bracket 235. The beamsplitter assembly 230 may be fixed to the housing 210 through a hole formed in the stopper 237 and a fixture 238.

[0190] The coupling relationship between the beamsplitter assembly 230 and the housing 210 will be described in more detail with reference to FIG. 18. As shown in FIG. 18, the housing 210 may include a slot 212 that is inwardly inclined. Since the slot 212 is formed to be inclined with respect to the side surface and the bottom surface of the housing 210, the beamsplitter assembly 230 may be easily slid and inserted by the influence of gravity when inserted into the slot 212. Accordingly, when the beamsplitter assembly 230 is inserted into the slot 212, it may be seated at a designated position without an additional external force.

[0191] As the beamsplitter assembly 230 may be easily inserted into the slot 212, the beamsplitter assembly 230 may be easily removed from the housing 210 and replaced according to a user's need. That is, when the beamsplitter 234 needs to be replaced, the user may easily separate the beamsplitter assembly 230 from the housing 210, and then may selectively replace and reassemble the beamsplitter 234.

[0192] In addition, as described above, the slot 212 may be formed to communicate with the plurality of first passages 211 and the plurality of second passages 213. In an example, the slot 212 may have a form in which each of the first passage 211 and the second passage 213 extends in a third direction perpendicular to a plane including the first direction and the second direction passing through the housing 210.

[0193] In addition, the slot 212 may include grooves having shapes corresponding to each of the upper guide 232 and the lower guide 236. The upper guide 232 and the lower guide 236 may be inserted by sliding along the groove formed inside the slot 212. Accordingly, the beamsplitter assembly 230 may be stably inserted into the slot 212 without being distorted, and the stopper 237 may be mounted to be in close contact with a partial surface of the housing 210.

[0194] Since the slot 212 is formed in the housing 210, the beamsplitter assembly 230 may be inserted into or separated from the slot 212 even when the excitation lens-filter unit 220 and the emission lens-filter unit 250 are respectively fixed to the first passage 211 and the second passage 213. In this case, the slot 212 is formed between a first designated position and a second designated position provided in each of the first passage 211 and the second passage 213.

[0195] Condensing lens unit

[0196] Next, the condensing lens unit 240 according to an exemplary embodiment of the present disclosure will be described in more detail with reference to FIG. 19. FIG. 19 is an exploded perspective view of a condensing lens unit 240 according to an embodiment of the present disclosure. As illustrated in FIG. 19, the condensing lens unit 240 includes a condensing lens 241, a lens holder 242 formed to fix the condensing lens 241 to the lower surface of the housing 210, and a coupling member 243 for coupling the lens holder 242 to the housing 210.

[0197] As illustrated in FIG. 19, a lens hole 242a is formed in the lens holder 242 to allow light to pass therethrough, and a diameter of the lens hole 242a according to an embodiment of the disclosure may be smaller than a diameter of the condensing lens 241. As described above, the condensing lens 241 may be accommodated in the stepped part formed on the lower surface of the housing 210 and may be sandwiched and fixed between the lower surface of the housing 210 and the lens holder 242, and the shape of the lens holder 242 may be formed to engage with the shape of the lower surface of the housing 210. In addition, the lens holder 242 may be formed so that both sides thereof are engaged between the lower side surface of the housing 210 and the lower frame 320. The condensing lens 241 may be firmly fixed to the lower surface of the housing 210 by the lens holder 242 and the coupling member 243, and the components may be coupled in a sandwich manner while being engaged with each other, which allows the manufacturing of an optical module that is easy to assemble and has excellent durability.

[0198] In addition, since the condensing lens unit 240 is fixed to the lower surface of the housing 210, the condensing efficiency of the light passing therethrough is increased, thereby increasing the efficiency of the sample detection signal by up to 1.5 times. A condensing lens 241 may be provided for each optical path formed in the housing 210. Accordingly, since light may be intensively transmitted to an accurately intended sample well, a stable and highly reliable signal may be detected even when the body portion 200 is continuously moving.

[0199] In addition, when the excitation light irradiated through the opening 211a deviates from an intended position, the intensity of the detected signal is clearly changed by the condensing ability of the condensing lens 241. Since the alignment state between the body portion 200 and the reaction portion 10 may be monitored according to the intensity of the detected signal, the fluorescent material of the sample may be excited by efficiently condensing light on a preset position.

[0200] Frame unit and an excitation light detection unit

[0201] Next, the frame unit 300 and the excitation light detection unit 400 will be described in more detail with reference to FIG. 20. FIG. 20 is a perspective view illustrating a state in which a frame unit 300 and an excitation light detection unit 400 are coupled to each other according to an embodiment of the present disclosure.

[0202] As illustrated in FIG. 20, the frame unit 300 may include a support 310 and a lower frame 320. According to an embodiment of the present disclosure, the support 310 forms a vertical member of the frame unit 300, and the lower frame 320 forms a bottom surface. The support 310 protrudes upward from the lower frame 320 and is formed to mount the excitation light detection unit 400.

[0203] A bottom hole 321 may be formed in the lower frame 320 so that the light generated by the light source 110 and the light emitted from the sample 30 may pass therethrough. The bottom hole 321 may be formed in the same number as the number of optical units provided in the optical module. Each of the bottom holes 321 may be formed to be aligned with the condensing lens 241 and the opening 211a described above. That is, the center points of the condensing lens 241, the opening 211a, and the bottom hole 321 in one optical unit are positioned on the same line.

[0204] The support 310 protruding upward from the lower frame 320 supports the excitation light detection unit 400. The excitation light detection unit 400 may include a feedback control board 410 and an excitation light detector 420. Here, the feedback control board 410 may be a circuit board that can be substantially electrically connected and controlled by the excitation light detector 420. That is, the feedback control board 410 may be a printed circuit board (PCB) on which the excitation light detector 420 is mounted.

[0205] The support 310 may overlap at least a portion of both sides of the feedback control board 410 and may be coupled to the feedback control board 410. A hole is formed in the overlapping portion, so that a fixture such as a screw can be tightened while being inserted into the hole.

[0206] As described above, the excitation light detector 420 may detect a portion of the light generated by the light source 110. Light may be emitted from the light source 110, and a portion of the light may be reflected by the beamsplitter assembly 230 to reach the excitation light detector 420.

[0207] The excitation light detector 420 may distinguish the wavelength of light to detect the amount of light for each wavelength, or may detect the total amount of light regardless of the wavelength. For example, the excitation light detector 420 may be a photodiode, a photodiode array, a photo multiplier tube (PMT), a CCD image sensor, a CMOS image sensor, an avalanche photodiode (APD), or the like. The same number of excitation light detector(s) 420 may be provided as the number of optical unit(s) provided in the optical module. Also, the excitation light detector 420 may be aligned with the second passage 213 and provided on the feedback control board 410.

[0208] In an example, each of the first body portion 200A and the second body portion 200B of the optical signal detection device according to the present disclosure may be configured to have three optical paths. In this case, each of the body portions 200A and 200B may include three of the first passage 211, the excitation lens-filter unit 220, the beamsplitter 234, the excitation light detector 420, the condensing lens unit 240, the bottom hole 321, the second passage 213, the emission lens-filter unit 250, and the emission light detector 520.

[0209] In this case, the two body portions 200A and 200B may be coupled to each other with one frame unit 300 and the excitation light detection unit 400 interposed therebetween. The two body portions 200A and 200B are symmetrical to each other, and the excitation light detection unit 400 may include a plurality of excitation light detectors 420 on both sides of one feedback control board 410. That is, the excitation light detector 420 may be provided between the side surfaces of the first and second housings 210A and 210B facing each other.

[0210] Three light paths may be formed at both sides of the feedback control board 410 to form a total of six light paths. In another embodiment, a third body portion (not shown), a fourth body portion (not shown), and the like may be further provided, and accordingly, the frame unit 300 may be additionally configured, or the shape of the frame unit 300 may be partially modified.

[0211] Emission light detecting part and a temperature controlling part

[0212] Next, the emission light detection unit 500 and the temperature control unit 600 will be described with reference to FIG. 21. FIG. 21 is an exploded perspective view illustrating an emission light detection unit 500 and a temperature control unit 600 according to an embodiment of the present disclosure.

[0213] As shown in FIG. 21, the emission light detection unit 500 may include a printed circuit board 510 and an emission light detector 520 coupled to the printed circuit board 510. According to an embodiment of the disclosure, the printed circuit board 510 may be a printed circuit board (PCB) on which the emission light detector 520 is mounted.

[0214] The emission light emitted from the sample 30 passes through the condensing lens 241 and is reflected toward the emission lens-filter unit 250 by the beamsplitter 234 to reach the emission light detector 520. Similar to the excitation light detector 420, the emission light detector 520 may detect an optical signal by generating an electrical signal according to the intensity of the optical signal. The emission light detector 520 is formed to detect emission light emitted from an optical label included in the sample.

[0215] The emission light detector 520 may detect the amount of light for each wavelength by distinguishing the wavelength of the light, or may detect the total amount of light regardless of the wavelength. For example, the emission light detector 520 may be a photodiode, a photodiode array, a photomultiplier tube, a CCD image sensor, a CMOS image sensor, an avalanche photo diode (APD), or the like.

[0216] The emission light detector 520 may be fixed to one side of the printed circuit board 510, and a temperature adjusting unit 600 may be provided on the other side thereof. The temperature control unit 600 is configured to control the temperature of the emission light detector 520. As illustrated in FIG. 21, the temperature adjusting part 600 may include a heat radiating plate 610 and a thermoelectric element 620. In addition, the temperature control unit 600 may further include a thermoelectric element mount 630, and the thermoelectric element 620 may be fixed between the heat sink 610 and the printed circuit board 510 by the thermoelectric element mount 630.

[0217] Here, the thermoelectric element 620 may be a heating / cooling element such as a Peltier element, which may be controlled by an electrically coupled thermal control circuit. The heat sink 610 may include a plurality of cooling fins, and may be used to discharge heat together with the thermoelectric element 620 when the emission light detector 520 is heated by the emission light. Since the temperature of the emission light detector 520 is kept constant by the temperature adjusting unit 600, the influence of the temperature may be minimized to increase the reliability of the emission light detector 520.

[0218] Plurality of optical units and a modified example

[0219] According to the embodiment of the present disclosure shown in FIGS. 1 to 21, the light source unit 100, the body portion 200, the frame unit 300, the excitation light detection unit 400, the emission light detection unit 500, and the temperature adjustment unit 600 are coupled to form an optical module including a plurality of optical units. An optical module according to an embodiment of the present disclosure performs light irradiation-light detection while moving in a predetermined pattern over a reaction portion 10, in which reaction vessels accommodating samples is accommodated.

[0220] Each optical unit may include a first passage 211, an excitation lens-filter unit 220, a beamsplitter 234, an excitation light detector 420, a condensing lens 241, a second passage 213, an emission lens-filter unit 250, and an emission light detector 520. The light source unit 100 may include a light source 110 for each optical unit, but is not limited thereto. For example, the light source unit 100 may include a plurality of LEDs, a laser, an optical fiber, or the like as the light source 110. The control unit 20 may control a light emission operation of the light source 110, and may receive signals from the excitation light detector 420 and the emission light detector 520.

[0221] The optical signal detection device according to an embodiment of the present disclosure is slidable over a sample, and may be manufactured by determining the number of optical units according to the number of samples to be analyzed and work efficiency desired by a user. That is, the optical signal detection device may be easily manufactured and assembled according to the number of samples and a working speed required by a user, and may be manufactured at a reasonable cost.

[0222] For example, when analyzing a plurality of samples accommodated in a 96-well plate, an optical module including six optical units may be used. In this case, three first passages and three second passages may be formed to penetrate through the housings of the two symmetric body portions, respectively, and the two body portions may be coupled by the frame unit and the light source unit.

[0223] In another example, when it is desired to quickly analyze a small number of samples according to the needs of the user, the optical module according to another embodiment of the present disclosure may include two optical units. These components may form two light paths to analyze two samples simultaneously or sequentially. In this case, one first passage and one second passage may be formed through the housings of the two symmetric body portions, respectively, and the two body portions may be coupled by the frame unit and the light source unit. In another case, the two optical units may be disposed side by side in a housing of one body portion. That is, two first passages and two second passages may be formed penetrating through one housing side by side, and the frame unit and the light source unit may be coupled to the side surface and the upper portion of the housing, respectively.

[0224] In addition, when it is desired to quickly analyze a larger number of samples according to the needs of the user, the optical module according to another embodiment of the present disclosure may include 12 optical units. These components may form 12 light paths to analyze at least 12 samples simultaneously or sequentially. The arrangement of the twelve optical units may be made in various ways.

[0225] The above description is merely illustrative of the technical idea of the present disclosure, and those skilled in the art to which the present disclosure pertains will be able to make various modifications and variations without departing from the essential quality of the present disclosure.

[0226] Therefore, the embodiments disclosed in the present disclosure are not intended to limit the technical idea of the present disclosure, but to explain it, and the scope of the technical idea of the present disclosure is not limited by these embodiments. The protection scope of the present disclosure should be interpreted by the following claims, and all technical ideas within the scope equivalent thereto should be interpreted as being included in the scope of the present disclosure.

Claims

1.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device comprising:a light source unit comprising a light source for generating an excitation light;a body portion coupled to the light source unit and having a plurality of passages formed therethrough; andan emission light detector provided at a side of the body portion, for detecting an emission light emitted from the sample,wherein a plurality of recesses, in which the reaction vessel is disposed, are provided below the body portion,wherein a distance between two adjacent said recesses is formed to be spaced apart by a first distance, anda distance between respective end portions of two adjacent said passages is formed to be spaced apart by a second distance, andthe second distance is larger than the first distance.2.The optical signal detection device of claim 1, wherein the body portion moves according to a predetermined pattern with respect to a reaction portion that comprises the plurality of recesses.3.The optical signal detection device of claim 1, wherein the second distance is a multiple of the first distance.4.The optical signal detection device of claim 1, wherein light of different wavelengths is aligned and irradiated to different recesses through the plurality of passages.5.The optical signal detection device of claim 1, wherein the body portion comprises a housing through which the plurality of passages are formed,wherein the plurality of passages comprise a plurality of first passages passing through the housing in a first direction and a plurality of second passages passing through the housing in a second direction,wherein the second passages are formed to match and intersect respective said first passages,wherein an opening is formed at an end portion of each of the plurality of first passages to face a reaction portion comprising the plurality of recesses,wherein a distance between two adjacent said openings is formed to be spaced apart by the second distance.6.The optical signal detection device of claim 5, wherein a slot communicating with a plurality of spaces where the plurality of first passages and the plurality of second passages intersect is further formed inside the housing.7.The optical signal detection device of claim 6, wherein a beamsplitter is provided through the slot in each of the spaces where the plurality of first passages and the plurality of second passages intersect.8.The optical signal detection device of claim 5, wherein an excitation lens-filter unit comprising an excitation filter and an excitation lens is provided in the first passage, andan emission lens-filter unit comprising an emission filter and an emission lens is provided in the second passage.9.The optical signal detection device of claim 8, wherein a first stepped part protruding inward is formed in the first passage, such that the excitation lens-filter unit is caught by the first stepped part, anda second stepped part protruding inward is formed in the second passage, such that the emission lens-filter unit is caught by the second stepped part.10.The optical signal detection device of claim 5, wherein the body portion comprises two housings, andthe two housings are a first housing and a second housing which are symmetrical to each other and are separable from each other.11.The optical signal detection device of claim 10, further comprising a frame unit connecting the first housing and the second housing,wherein the frame unit comprises a lower frame coupled to lower portions of the first and second housings, and a support coupled to opposing side surfaces of the first and second housings.12.The optical signal detection device of claim 11, wherein the support protrudes upward from the lower frame.13.The optical signal detection device of claim 11, wherein each of the first and second housings further comprises a condensing lens unit comprising a condensing lens positioned on a same vertical line as each of the plurality of first passages, and wherein the condensing lens unit is positioned between the first and second housings and the lower frame.14.The optical signal detection device of claim 11, further comprising: an excitation light detector for detecting a part of the excitation light passing through each of the plurality of first passages.15.The optical signal detection device of claim 14, wherein the excitation light detector is provided between the opposing side surfaces of the first and second housings.16.The optical signal detection device of claim 14, wherein the excitation light detector is provided on both sides of a feedback control board supported by the support so as to be aligned with each of the second passages.17.The optical signal detection device of claim 14, wherein the light source unit comprises a plurality of light sources, and each of the excitation light detectors is configured to monitor an operating state of a designated light source.18.The optical signal detection device of claim 17, wherein the light source unit further comprises a light source control board for controlling the light source,wherein the light source control board controls a light output value of each of the light sources according to a signal transmitted from each of the excitation light detectors.19.The optical signal detection device of claim 18, wherein, when at least some of the signals generated from the excitation light detector deviate from a preset parameter, the movement of the body portion is stopped.20.The optical signal detection device of claim 1, wherein the second distance is at least 18 mm.21.The optical signal detection device of claim 1, wherein the plurality of passages comprise a plurality of first passages passing through the body portion in a first direction,wherein the first passages are designated for each of the plurality of light sources, andwherein the plurality of light sources simultaneously emit light.22.The optical signal detection device of claim 21, wherein the number of light sources is six, and the first passage is designated for each of the six light sources, and the first passage is formed to pass through the body portion to form a 3X2 matrix.23.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler and moving according to a predetermined pattern, the device comprising:a reaction portion comprising a plurality of recesses formed so that the reaction vessel may be disposed therein, wherein any one of the plurality of recesses is formed to be spaced apart from another adjacent recess by a first distance;a light source unit comprising a plurality of light sources and a light source control board on which the plurality of light sources are installed, wherein one of the plurality of light sources is formed to be spaced apart from another adjacent light source by a second distance greater than the first distance;a body portion coupled to a lower portion of the light source part, determining a path of light emitted from each of the light sources, and comprising a first housing and a second housing which are symmetrical to each other and are separable from each other, wherein each of the first and second housings has a first passage that is matched with each of the plurality of light sources to penetrate through the first or second housing in a first direction, a second passage that is matched with each of the first passages to intersect each other and penetrates through the first or second housing in a second direction, and a slot that is recessed in a third direction inside the first or second housing, wherein the slot is a slot communicating with a space in which a plurality of first passages formed side by side and a plurality of second passages formed side by side intersect, wherein a beamsplitter is positioned in each of the spaces where the first passage, the second passage, and the slot intersect, wherein an excitation lens-filter unit comprises an excitation filter and an excitation lens is disposed in each of the first passages, wherein an emission lens-filter unit comprises an emission filter and an emission lens is disposed in each of the second passages, wherein a condensing lens unit couples to a lower portion of each of the first passages;a frame unit connecting the first and second housings and comprising a lower frame positioned below the condensing lens unit and a support protruding upward from the lower frame and coupled to opposing side surfaces of the first and second housings;an emission light detection unit coupled to the outside of each of the first and second housings and comprising an emission light detector for detecting light emitted from the sample;an excitation light detection unit detecting a part of light emitted from each of the light sources, and comprising, a feedback control board which is arranged between opposing sides of the first and second housings and supported by being coupled to the support and, a plurality of excitation light detectors which are formed on both sides of the feedback control board.24.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device comprising:a light source unit comprising a light source for generating an excitation light;a housing coupled to the light source unit, comprising a plurality of passages penetrating therethrough and an inwardly inclining slot cut therein;an emission light detector provided at a side of the housing, for detecting an emission light emitted from the sample; anda beamsplitter assembly comprising a beamsplitter for each of the passages, wherein the beamsplitter assembly is slidably inserted into and coupled with the slot.25.The optical signal detection device of claim 24, wherein the slot is formed to be inclined with respect to a side surface and a bottom surface of the housing and communicates with each of the passages.26.The optical signal detection device of claim 25, wherein the plurality of passages comprise a plurality of first passages penetrating through the housing in a first direction and a plurality of second passages penetrating through the housing in a second direction,wherein each of the second passages is formed to match and intersect the first passages, andwherein the slot extends through the housing in a third direction to communicate with the plurality of first passages and the plurality of second passages.27.The optical signal detection device of claim 24, wherein the beamsplitter assembly is slidable in the slot under the influence of gravity.28.The optical signal detection device of claim 24, wherein the beamsplitter assembly further comprises a first bracket and a second bracket coupled to the first bracket,wherein the beamsplitter is sandwiched and fixed between the first bracket and the second bracket.29.The optical signal detection device of claim 28, wherein the first bracket comprises an upper guide formed to protrude from a partial surface thereof,and the second bracket comprises a lower guide formed to protrude from a partial surface thereof,wherein the slot comprises grooves having shapes corresponding to each of the upper guide and the lower guide, and each of the upper guide and the lower guide is inserted to slide along the grooves.30.The optical signal detection device of claim 28, wherein the plurality of beamsplitters are spaced apart from each other by a predetermined distance and are positioned and fixed between the first bracket and the second bracket.31.The optical signal detection device of claim 24, wherein the plurality of beamsplitters are dichroic beamsplitters having different passbands.32.The optical signal detection device of claim 24, wherein at least one protruding guide is formed on a portion of a surface of the beamsplitter assembly, the slot comprises a groove having a shape corresponding to each of the guides, and the guide is slidably inserted along the groove.33.The optical signal detection device of claim 24, wherein the beamsplitter assembly comprises a stopper configured to determine a position of the beamsplitter assembly by being caught by the housing.34.The optical signal detection device of claim 33, wherein the stopper is a protrusion formed by extending an upper edge of the beamsplitter assembly in the direction of one side or both sides of the upper edge.35.The optical signal detection device of claim 34, wherein the stopper is fixed to a partial surface of the housing in which the slot is formed by a fixture.36.The optical signal detection device of claim 26, wherein an excitation lens-filter unit for filtering the excitation light is provided in the first passage, an emission lens-filter unit for filtering the emission light is provided in the second passage, and each of the excitation lens-filter unit and the emission lens-filter unit is fixedly inserted into a first designated position and a second designated position provided in the first passage and the second passage.37.The optical signal detection device of claim 36, wherein the slot is formed between the first designated position and the second designated position.38.The optical signal detection device of claim 26, wherein the beamsplitter assembly is insertable into or detachable from the housing in a state in which the excitation lens-filter unit and the emission lens-filter unit are located at the first designated position and the second designated position, respectively.39.The optical signal detection device of claim 24, further comprising: an excitation light detector coupled to the other side of the housing, for detecting a part of the light generated from the light source, which is reflected by the beamsplitter.40.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device comprising:a light source unit comprising a light source for generating an excitation light;a housing coupled to the light source unit and comprising a plurality of first passages penetrating through the housing in a first direction, a plurality of second passages matching the plurality of first passages and penetrating through the housing in a second direction, and a slot communicating with crossing points of the plurality of first passages and the plurality of second passages and inclined inwardly;an excitation lens-filter unit provided in the plurality of first passages to filter the excitation light;an emission lens-filter unit provided in the plurality of second passages to filter the emission light;an emission light detector provided at a side of the housing to detect emission light emitted from the sample; anda beamsplitter assembly comprising a first bracket, a second bracket coupled to the first bracket, a stopper extending from the first bracket or the second bracket to be caught by the housing outside of the slot, and a beamsplitter sandwiched and fixed between the first bracket and the second bracket and spaced apart from each other at a predetermined distance with respect to the crossing points, wherein the beamsplitter assembly is slidable and insertable or separable into or from the housing in a state in which the excitation lens-filter unit and the emission lens-filter unit are respectively fixed to the first passages and the second passages.41.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the optical signal detection device comprising:a light source for generating an excitation light;a housing having a passage penetrating therethrough; andan emission light detector coupled to a side of the housing, for detecting an emission light emitted from the sample,wherein a lens-filter unit is inserted and installed in the passage, andwherein the lens-filter unit comprises: a lens; a mount on which the lens is mounted; and a filter fixed to be spaced apart from the lens by a predetermined distance by the mount.42.The optical signal detection device of claim 41, wherein the mount comprises:a gripping portion configured to fix the lens;a filter coupling portion configured to fix the filter; anda barrel-shaped barrel portion formed between the gripping portion and the filter coupling portion and configured to keep the lens and the filter spaced apart from each other by a predetermined distance.43.The optical signal detection device of claim 42, wherein the lens and the filter are spaced apart from each other by a stepped part formed at two ends of the barrel portion.44.The optical signal detection device of claim 42, wherein the gripping portion comprises: a portion surrounding a side surface of the lens and connected to the barrel portion; and a plurality of fingers formed to surround an edge portion of the lens.45.The optical signal detection device of claim 44, wherein the lens is a convex lens, and wherein the plurality of fingers grip the lens such that a convex surface of the lens faces an outside of the mount.46.The optical signal detection device of claim 45, wherein the gripping portion is formed of a flexible material, and the plurality of fingers are pressed toward the lens as the lens-filter unit is inserted into the passage.47.The optical signal detection device of claim 42, wherein the filter coupling portion surrounds at least a portion of an outer diameter of the filter.48.The optical signal detection device of claim 47, wherein a gap is formed at a portion of a circumference of the filter coupling portion, and an adhesive is injected into a side surface of the filter through the gap.49.The optical signal detection device of claim 48, wherein the adhesive is a bonding solution injected through the gap after the filter is inserted into the filter coupling portion and capable of being cured with UV light.50.The optical signal detection device of claim 42, wherein each of the lens and the filter has a diameter larger than an inner diameter of the barrel portion.51.The optical signal detection device of claim 42, wherein a fixing groove recessed to a predetermined depth is formed at an outer circumference of the barrel portion.52.The optical signal detection device of claim 51, wherein the housing further comprises a through-hole penetrating through a portion of the passage, and a fixing portion inserted and fixed through the through-hole,wherein after the lens-filter unit is inserted into the passage of the housing, a position of the lens-filter unit is fixed as at least a portion of the fixing portion is accommodated in the fixing groove.53.The optical signal detection device of claim 52, wherein the fixing portion is a screw-shaped component and is configured to be fastened through the through-hole to be received in at least a portion of the fixing groove.54.The optical signal detection device of claim 41, wherein the mount is formed of a flexible material.55.The optical signal detection device of claim 42, wherein a stepped part is formed inside the passage of the housing, andthe gripping portion or the filter coupling portion is caught by the stepped part such that the lens-filter unit is seated on the passage.56.The optical signal detection device of claim 41, wherein the passage of the housing comprises a first passage penetrating through the housing in a first direction and a second passage penetrating through the housing in a second direction, andthe lens-filter unit comprises an excitation lens-filter unit and an emission lens-filter unit that are inserted into the first passage and the second passage, respectively.57.The optical signal detection device of claim 56, wherein the excitation lens-filter unit and the emission lens-filter unit comprise filters having different passbands.58.The optical signal detection device of claim 56, wherein a beamsplitter is provided in a space in which the first passage and the second passage intersect inside the housing.59.An optical signal detection device for analyzing a sample in a reaction vessel provided in a thermal cycler, the device comprising:a light source for generating an excitation light;a housing having a passage penetrating therethrough; andan emission light detector coupled to a side of the housing, for detecting an emission light emitted from the sample, wherein a lens-filter unit is inserted and installed in the passage, and the lens-filter unit comprises: a lens; a mount on which the lens is mounted; and a filter fixed to be spaced apart from the lens by a predetermined distance by the mount, wherein the mount comprises: a gripping portion comprising a portion surrounding a side surface of the lens and a plurality of fingers formed to surround an edge portion of the lens to fix the lens; a filter coupling portion surrounding at least a portion of an outer diameter of the filter and into which an adhesive is injected through a gap formed in a portion of a circumference thereof to fix the filter; and a barrel-shaped barrel portion formed between the gripping portion and the filter coupling portion to space the lens and the filter by a predetermined gap and having a fixing groove recessed at a predetermined depth in an outer circumference thereof,wherein the housing further comprises: a through-hole penetrating a portion of the passage; and a fixing portion inserted and fixed through the through-hole, andwherein after the lens-filter unit is inserted into the passage of the housing and caught by the stepped part formed in the passage of the housing to be seated, a position of the lens-filter unit is fixed as at least a portion of the fixing portion is accommodated in the fixing groove.

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