KR102360041B1 - Optical measurement system supporting both time-resolved fluorescence and visible light measurements - Google Patents

Abstract

The present invention discloses an optical measurement system which supports a fluorescence detection mode for performing time-resolved fluorescence measurement and a visible light detection mode for performing visible light measurement. The optical measurement system comprises: a strip unit on which a fluorescent particle-analysis target compound formed by combination of a fluorescent particle emitting light of a second wavelength by absorbing light of a first wavelength and an analysis target is disposed; a light source unit including a first light source unit which irradiates the strip unit with light of a wavelength band including the first wavelength, and a second light source unit which irradiates the strip unit with light of visible light wavelength band; and a sensing unit which is provided to detect the light of the second wavelength or the visible light emitted from the strip unit. The optical measurement system detects an accurate signal by using various filters.

Description

Optical measurement system supporting both time-resolved fluorescence and visible light measurements

The present invention relates to an optical measurement system that supports both time-division fluorescence and visible light measurement with one optical system.

Fluorescence occurs when a molecule is emitted by an electronic transition when a molecule absorbs a photon and the excited state returns to its ground state. Fluorescent materials absorb energy at one wavelength and re-emit it at another wavelength. Fluorescent materials, including inorganic materials and organic materials, are used as fluorescent dyes or pigments such as fluorescent inks and fluorescent paints.

As the development of biomaterial diagnosis and detection technology is rapidly progressing, studies to apply fluorescent materials to biological and biomedical research are in progress. Fluorescent materials may be advantageous for detection of trace samples due to their high sensitivity. However, most fluorescent dyes have a fluorescence duration in the nanosecond range, and the difference between the excitation wavelength and the fluorescence wavelength is very close to 10 to 20 nm, which raises a problem in improving the detection limit. That is, since most fluorescent dyes have very short fluorescence duration, in the conventional fluorescence detection, a light source for excitation and fluorescence measurement by emission were simultaneously performed. Such a fluorescence detection method is difficult to completely remove the excitation light from the detected fluorescence, and thus a background fluorescence signal such as autofluorescence is not removed from the analysis target, thereby limiting detection sensitivity.

Most of domestic and foreign time-division fluorescence analysis techniques are approaches and attempts based on background principles and theories. In the area of diagnostic kits, there was a limit to presenting improved detection sensitivity compared to existing detection systems. In addition, since the analyte undergoes enzyme treatment and/or washing, the fluorescence detection method is complicated and takes a long time. The optical measurement system has been difficult to be used in small hospitals, emergency rooms, homes, etc. due to problems of large size and/or high cost.

Although the measurement using fluorescence has excellent detection sensitivity, the measurement system is complicated, and the measurement using visible light has a problem in that the required system is simple, but the detection sensitivity is relatively low. An object of the present invention to solve the above problems is to provide an optical measurement system that supports both time-division fluorescence and visible light measurement.

An embodiment of the present invention for achieving the above object may provide an optical measurement system capable of accurately detecting a signal using various filters.

An optical measurement system according to an aspect of the present invention is an optical measurement system that supports a fluorescence detection mode for performing time-division fluorescence measurement and a visible light detection mode for performing visible light measurement, wherein the optical measurement system absorbs light of a first wavelength a strip unit in which a fluorescent particle-analyzing object combination formed by combining a fluorescent particle emitting light of a second wavelength and an analyte to be analyzed; a light source unit including a first light source unit capable of irradiating light in a wavelength band including a first wavelength to the strip unit, and a second light source unit capable of irradiating light in a visible light wavelength band to the strip unit; and a sensing unit provided to detect light or visible light of a second wavelength emitted from the strip unit.

A filter converter including a plurality of filters provided to filter light emitted from the strip unit and incident to the sensing unit, a filter converter selectively exposing any one of the plurality of filters to the outside; may include.

The optical measurement system further includes a control unit capable of controlling the light source unit and the filter converter, wherein the plurality of filters include a first filter selectively transmitting a second wavelength and a second filter removing an infrared wavelength from the filtered light. and, when in the fluorescence measurement mode, the control unit controls the first light source unit to repeat switching between on mode and off mode, controls the filter switcher to expose the first filter to the outside, and 1 When the light source unit is turned off, the sensing unit is controlled to detect fluorescence emitted from the strip unit, and in a visible light measurement mode, the control unit controls the second light source unit to be in an on mode, and the second filter is exposed to the outside. It is possible to control the filter converter as much as possible.

The strip portion includes a substrate; a developing film disposed on the substrate; a sample pad disposed on the development layer and on which an analyte is disposed; an emission pad disposed on the developing film and onto which fluorescent particles are adsorbed; and a detection region formed on the development film and disposed with a capture material capable of binding to an analyte portion of the fluorescent particle-analyte complex, wherein the analyte of the sample pad flows through the development film to induce fluorescence of the emission pad is combined with the particles to form a fluorescent particle-analyzed complex, the fluorescent particle-analyzed complex flows through the developing film to reach the detection area, and the light source unit causes the fluorescent particle-analyzed complex to be formed by the capture material. The fixed detection region may be irradiated with light, and the sensing unit may measure light emitted from the detection region.

The filter converter includes a support frame to which at least one of the first filter and the second filter is fixed; an actuator for slidingly moving the support frame; a guide rail for guiding the movement of the support frame; and a slide coupling part fixed to a side end of the support frame and slidably coupled to the guide rail.

According to the present invention, it is possible to provide an optical measurement system supporting both time-division fluorescence and visible light measurement.

According to the present invention, accurate data can be provided to a user by acquiring a plurality of images using various filters.

1 is a plan view showing a strip portion according to an embodiment of the present invention.
FIG. 2 is a cross-sectional view taken along line AB of FIG. 1 .
3 to 5 are schematic diagrams illustrating a method for detecting an analyte according to an embodiment of the present invention.
6 is a schematic diagram illustrating an optical measurement system according to an embodiment of the present invention.
7 is a view showing a perspective view (a) and a bottom perspective view (b) of a filter converter according to an embodiment in the optical measurement system shown in FIG. 6 .
FIG. 8 is a view showing the inside of the filter converter shown in FIG. 7 .
9 to 11 show images displayed on an image display unit according to embodiments of the present invention.
12 is a perspective view illustrating a filter converter according to another embodiment in the optical measurement system shown in FIG. 6 .
Fig. 13 is a side cross-sectional view of the filter converter shown in Fig. 12;
FIG. 14 is a view showing the filter body shown in FIG. 13 .

Since the present invention can have various changes and can have various embodiments, specific embodiments are illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing each figure, like reference numerals have been used for like elements.

Terms such as first, second, A, and B may be used to describe various elements, but the elements should not be limited by the terms. The above terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component. The term “and/or” includes a combination of a plurality of related listed items or any of a plurality of related listed items.

When a component is referred to as being “connected” or “connected” to another component, it may be directly connected or connected to the other component, but it is understood that other components may exist in between. it should be On the other hand, when it is said that a certain element is "directly connected" or "directly connected" to another element, it should be understood that the other element does not exist in the middle.

The terms used in the present application are only used to describe specific embodiments, and are not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly dictates otherwise. In the present application, terms such as “comprise” or “have” are intended to designate that a feature, number, step, operation, component, part, or combination thereof described in the specification exists, but one or more other features It should be understood that this does not preclude the existence or addition of numbers, steps, operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present application. does not

Hereinafter, preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings. In describing the present invention, in order to facilitate the overall understanding, the same reference numerals are used for the same components in the drawings, and duplicate descriptions of the same components are omitted.

The terms "upper", "lower", "left", "right", etc. used below are defined based on the drawings, and the shape and position of each component is not limited by these terms.

1 is a plan view showing a strip portion according to an embodiment of the present invention. FIG. 2 is a cross-sectional view taken along line A-B of FIG. 1 .

1 and 2 , the strip portion 10 may include a substrate 100 , a development layer 110 , a sample pad 120 , an emission pad 130 , and an absorption pad 140 .

The substrate 100 may support the strip portion 10 . The substrate 100 may include a material that does not react with the analyte and the complex of the analyte, or does not chemically or physically interact. The substrate 100 may include a natural or synthetic organic material and/or an inorganic material, but is not limited thereto and may include various materials. In one example, the substrate 100 may include polyethylene, polyester, polypropylene, poly(4-methylbutek), polystyrene, polymethacrylate, poly(ethylene terephthalate), and/or nylon, poly(vinyl butyrate), or the like. It may contain organic matter. As another example, the substrate 100 may include an inorganic material such as glass, ceramic, and/or metal. The substrate 100 may include a water-insoluble and non-porous material.

The sample pad 120 may be disposed on the development layer 110 to be adjacent to one side 110a (or “one end”) of the development layer 110 . An analyte (not shown) may be provided on the sample pad 120 . The sample pad 120 may function to filter insoluble particles included in the analyte. For example, the sample pad 120 may include, but is not limited to, cellulose filter paper or glass fiber filter paper, and may include various materials.

The release pad 130 may be disposed on the development layer 110 . The release pad 130 may be disposed adjacent to the sample pad 120 . The release pad 130 may be further spaced apart from the one side 110a of the development layer 110 than the sample pad 120 . The emission pad 130 may be provided in a state in which a fluorescent particle-labeled detector is adsorbed. The release pad 130 may include, but is not limited to, glass fiber, cellulose, and/or polyester. The release pad 130 may further include a stabilizer and/or a blocking agent. For example, the stabilizing agent may include saccharides such as sucrose and/or trehalose, and the blocking agent may include proteins such as bovine serum albumin, gelatin, casein, and/or skim milk. By the stabilizer, the intensity of light of the second wavelength emitted from the fluorescent particle and the fluorescent particle-analyzed object combination to be described later in FIG. 5 may be increased.

The development layer 110 may be provided (or disposed) on the substrate 100 . As an example, the developing film 110 may include natural rubber such as cellulose, cellulose acetate, and/or cellulose nitrate. As another example, the developing film 110 may include a synthetic polymer such as polyacrylonitrile, polyamide, and/or polyether, but is not limited thereto and may include various materials. The development layer 110 may have a detection area T and a control area C. Referring to FIG. In other words, the detection region T may be formed on one area of the surface of the development film 110 , and the contrast region C may be formed on the other area of the surface of the development film 110 . The detection region T and the control region C are interposed between the emission pad 130 and the absorption pad 140 , and the control region C may be adjacent to the emission pad 130 than the detection region T. . That is, in the left and right direction from one side 110a to the other side 110b of the development film 110 , the emission pad 130 , the detection region T, the control region C, and the absorption pad 140 are sequentially arranged. array?d can be. A plurality of detection regions T may be provided.

The absorbent pad 140 may be disposed on the development layer 110 to be adjacent to the other side 110b (or “the other end”) of the development layer 110 . The other side 110b may face the one side 110a. The absorbent pad 140 is provided on the sample pad 120 and the release pad 130 , and may absorb solvents flowing through the surface and/or inside of the development layer 110 . Accordingly, the analyte 200 and the fluorescent particle-analyzed object conjugate 250 may move along the development film 110 to the detection region T and the control region C by capillary force.

Hereinafter, a fluorescence detection method according to an embodiment of the present invention will be described.

3 to 5 are schematic diagrams illustrating a method for detecting an analyte according to an embodiment of the present invention. Hereinafter, content that overlaps with those described above will be omitted.

3 to 5 , the analyte 200 may be provided on the sample pad 120 . In the present specification, the analyte 200 may refer to a compound or composition to be analyzed included in a sample. In an embodiment, the analyte 200 may be of a single type or multiple types. The analyte 200 may include an antigen, an antibody, a nucleic acid, and/or a hapten.

Fluorescent particles P labeled with the detector 210 may be provided on the emission pad 130 . The fluorescent particle P may include a lanthanide complex. For example, the fluorescent particle P may include a lanthanide element and ligands bound to the lanthanide element. The lanthanide element may include europium (III), terbium (III), samarium (III), dysprosium, and/or a combination thereof. The lanthanide complex may exhibit stronger fluorescence intensity than gold. According to the present invention, since the fluorescent particle (P) contains the lanthanide complex, the intensity of fluorescence generated from the fluorescent particle (P) may be improved. The fluorescent particles P may have a diameter of approximately 100 nm to 590 nm. When the fluorescent particles P have an average diameter of less than 100 nm, fluorescence may not be detected from the fluorescent particles P. When the fluorescent particles P have an average diameter greater than 590 nm, it may be difficult for the fluorescent particles P to move along the development layer 110 from the emission pad 130 .

The detector 210 may correspond to the analysis target 200 . That is, the detector 210 may be determined according to the analysis target 200 . For example, the detector 210 may include an antibody, antigen, peptide, and/or protein capable of binding specifically or non-specifically to the analyte 200, but is not limited thereto, and may include various substances. .

The analyte 200 may move from the sample pad 120 to the emission pad 130 and may be coupled to the detector 210 labeled with the fluorescent particle P included in the emission pad 130 . The fluorescent particle P may be combined with the analyte 200 by the detector 210 to form the fluorescent particle-analyzed object combination 250 . When several types of analysis objects 200 are provided, the detectors 210 labeled with various types of fluorescent particles P may be provided on the sample pad 120 . As another example, when there are several types of analysis objects 200 , a plurality of sample pads 120 may be provided. Each of the sample pads 120 may include different types of fluorescent particles P and detectors 210 labeled with the fluorescent particles P. Accordingly, the fluorescent particles P may be selectively combined with the analytes 200 by the detectors 210 to form fluorescent particle-analyzed object combinations 250 . Hereinafter, a method for detecting the singular analyte 200 will be described, but the present invention is not limited to the singular analyte 200 . Fluorescent particles P bound to the detector 210 may be provided in excess, so that some of them may react with the analyte 200 , while others may remain.

The fluorescent particle-analysis target conjugate 250 may reach the detection area T of the developing film 110 . The detection region T is provided between the emission pad 130 and the absorption pad 140 on the development layer 110 , and may be a region including the first capture material 220 . The first capture material 220 may interact with the fluorescent particle-analyte complex 250 so that the fluorescent particle-analyte complex 250 may be immobilized in the detection region T. For example, the first capture material 220 may be specifically bound to a portion of the analyte 200 constituting the fluorescent particle-analyte competitor 250 . The fluorescent particles P remaining after forming the fluorescent particle-analysis target conjugate 250 may not interact with the first capture material 220 . The remaining fluorescent particles P may pass through the detection region T and move to the control region C.

The control region C is provided between the detection region T and the absorption pad 140 , and may be a region including the second capture material 230 . The fluorescent particles P may interact with the second capture material 230 of the control region C to be fixed to the control region C. Light of the first wavelength incident from the light source unit (not shown) may be irradiated to the detection area T and the control area C. The light source unit may be disposed on the developing film 110 to be spaced apart from the developing film 110 . The fluorescent particle-analysis object combination 250 on the detection region T and the fluorescent particle P on the control region C may absorb light of a first wavelength and emit light of a second wavelength. Whether or not the light of the second wavelength is emitted from the control region (C) may determine whether the fluorescent particles (P) have moved to the control region (C). The speed at which the fluorescent particles P and the fluorescent particle-analyzed compound 250 move on the development layer 110 may be the same or similar. The wavelength and intensity of light emitted from the detection region T may be measured to perform qualitative/quantitative analysis of the analyte 200 . In this case, the qualitative/quantitative analysis of the analyte 200 may be performed by measuring light emitted from the detection region T when light of the second wavelength is emitted from the control region C.

According to an embodiment, fluorescence (eg, whether light of the second wavelength is generated) of the control region C and the detection region T may be observed with the naked eye. Accordingly, the presence or absence of the analysis target 200 can be easily confirmed with the naked eye.

Fluorescence measurement of the fluorescent particle-analysis target conjugate 250 according to the present invention may be performed by a time division detection method. For example, the light source unit may repeat an on mode in which light is provided to the strip unit 10 and an off mode in which light is not provided to the strip unit 10 . When the light of the second wavelength is measured in the on mode, autofluorescence generated when the fluorescent particle-analysis target conjugate 250 is excited may also be measured. According to an embodiment, the measurement of fluorescence may be performed in an off mode. Since the fluorescent particle (P) of the present invention includes a lanthanide complex, the duration of fluorescence in the off mode may be long. For example, the fluorescent particle P may exhibit a fluorescence duration of 10 ms to 1000 ms. Accordingly, the wavelength and intensity of the light emitted by the fluorescent particle-analyzed object combination 250 in the off mode may be measured. In this case, autofluorescence of the fluorescent particle-analysis target conjugate 250 is not detected, and thus a background signal may decrease. According to the present invention, the detection sensitivity of the fluorescent particle-analyzed object conjugate 250 may be improved.

Hereinafter, the optical measurement system of this invention is demonstrated.

6 is a schematic diagram illustrating an optical measurement system according to an embodiment of the present invention.

Referring to FIG. 6 , the optical measurement system 1 (or "optical measurement device") includes a strip unit 10 , a light source unit 20 , a sensing unit 30 , a control unit 40 , an image display unit 50 , It may include at least one of the input unit 51 , the filter changer 60 , and the external device 53 .

The light source unit 20 may irradiate light to the strip unit 10 . The light source unit 20 may include a halogen lamp, a mercury lamp, a xenon quadrilateral tube, an LED, and/or a diode laser. Since the LED has a small volume, the optical measurement system 1 using the LED as the light source unit 20 can be downsized. In addition, the optical measurement system 1 using the LED as the light source unit 20 may exhibit high energy conversion efficiency.

The light source unit 20 may include a plurality of light source units 20 . The plurality of light source units 20 may include a first light source unit 21 and a second light source unit 22 . The first and second light source units 21 and 22 may irradiate light to the strip unit 10 .

The light irradiated from the first light source unit 21 may have a wavelength of approximately 200 nm to 500 nm (or "first region band"). For example, when the fluorescent particles provided on the strip part 10 are europium complexes, the first light source part 21 may irradiate the strip part 10 with light including light having a wavelength of 333 nm.

The optical measurement system 1 of the present invention can use a time division detection method. The first light source unit 21 may repeat an on mode in which light is provided to the strip unit 10 and an off mode in which light is not provided to the strip unit 10 . That is, the first light source unit 21 may repeatedly blink. Since the afterglow of the on mode does not remain in the LED in the off mode, the optical measurement system 1 using the LED as the light source unit 20 may be suitable for the time division detection method.

If the duration of the on mode of the first light source unit 21 is too short (eg, less than 0.5 ms), the light provided from the first light source unit 21 may not be stabilized. In addition, the fluorescent particle-analyte complex may be indistinguishable to reach an excited state. Accordingly, in the off mode, the intensity of light emitted from the fluorescent particle and the fluorescent particle-analyzed object combination may be reduced. According to an embodiment, the duration of the on mode of the first light source unit 21 may be about 0.5 ms or more.

Meanwhile, the second light source unit 22 may emit light in a wavelength range (or "second region") different from that of the first light source unit 21 . The light irradiated from the second light source 22 may have a wavelength of approximately 400 nm to 700 nm corresponding to the visible ray region. The second light source unit 22 may operate in an on mode that provides light to the strip unit 10 and an off mode that does not provide light to the strip unit 10 . The second light source unit 22 may be switched from an on mode to an off mode, or may be switched from an off mode to an on mode.

Referring to FIG. 6 together with FIG. 1 , the strip part 10 may be the same as the strip part 10 described in the example of FIG. 1 above. The fluorescent particle-analysis target complex included in the strip unit 10 may receive light of a first wavelength from the first light source unit 21 and emit light of a second wavelength as described with reference to FIGS. 3 to 5 . The strip portion 10 may be provided on the stage 11 . The stage 11 is movable in the horizontal direction, so that misalignment of the strip portion 10 can be prevented. Accordingly, light emitted from the first light source unit 21 may be irradiated to the detection area T and the contrast area C of the strip unit 10 .

In addition, the stream unit 10 may receive light of a third wavelength from the second light source unit 22 , and the strip unit 10 (or the fluorescent particle-analyzed object combination 250 , or the analyte 200). may reflect, refract, and scatter the light of the second light source unit 22 .

Referring back to FIG. 6 , the sensing unit 30 may be disposed adjacent to the strip unit 10 . The sensing unit 30 may include CCD and/or CMOS. The sensing unit 30 may sense the wavelength and intensity of light emitted from the strip unit 10 and convert it into an electrical signal.

The controller 40 may include a field programmable gate array (FPGA). The control unit 40 amplifies the electrical signal sensed by the sensing unit 30 and may function to process data. The control unit 40 may provide an electrical signal to the light source unit 20 to control the on mode and the off mode of the light source unit 20 . The controller 40 may independently control on/off of the first light source unit 21 and on/off of the second light source unit 22 . In this case, the control unit 40 may process the electrical signal received from the sensing unit 30 and transmit it to the image display unit 50 . Also, the control unit 40 may provide an electrical signal to the filter changer 60 to control the filter changer 60 .

7 is a view showing a perspective view (a) and a bottom perspective view (b) of a filter converter according to an embodiment in the optical measurement system shown in FIG. 6 . FIG. 8 is a view showing the inside of the filter converter shown in FIG. 7 .

6 to 8 , the filter converter 60 may be disposed between the strip unit 10 (or the stage 11 ) and the sensing unit 30 . The filter converter 60 may filter the light emitted from the strip unit 10 and incident to the sensing unit 30 .

The filter converter 60 includes a housing 61 in which an inner space 61c is formed and through-holes 61a and 61b are formed, and a filter 64 that filters light passing through the through-holes 61a and 61b; It may include a support frame 65 on which the filter 64 is disposed, and an actuator 67 for moving the support frame 65 . The filter 64 may include a plurality of filters 64 , and the plurality of filters 64 may include a first filter 62 and a second filter 63 . A combination of the support frame 65 and the at least one filter 64 may be referred to as a filter body 66 .

One end 61b of the through-holes 61a and 61b may be opened toward the strip portion 10 , and the other end 61b of the through-holes 61a and 61b may be opened toward the sensing unit 30 . Accordingly, light emitted from the strip unit 10 may pass through the through holes 61a and 61b to reach the sensing unit 30 . The through holes 61a and 61b may communicate with the inner space 61c of the housing 61 .

The filter body 66 may be disposed in the inner space 61c of the housing 61 and may be exposed to the outside of the housing 10 through the through holes 61a and 61b. The support frame 65 may be slidably moved by the actuator 67 . Any one of the first filter 62 and the second filter 63 disposed on the support frame 65 may be selectively exposed to the outside through the through holes 61a and 61b. The other one is disposed in the inner space 61c of the housing 61 and may be shielded so as not to be exposed to the outside through the through holes 61a and 61b. The actuator 67 may be controlled by the controller 40 .

For example, the actuator 67 includes a rotation motor 67a, a transport screw 67b rotated by the rotation motor 67a, and the transport screw 67b meshed with the transport screw 67b by the transport screw 67b. 67b) may include a moving nut 67c that slides in the extending direction. Since the moving nut 67c may be fixed to one end of the support frame 65 , the support frame 65 may also be slidably moved when the moving nut 67c is moved by the transport screw 67b. In addition, the filter converter 60 is disposed on the side opposite to the side on which the actuator 67 is disposed with respect to the filter body 66 and may include a guide rail 68 for guiding the movement of the support frame 65 . there is. The filter body 66 may include a slide coupling part 69 disposed at the side end of the support frame 65 and slidably coupled to the guide rail 68 and movably supported by the guide rail 68 . . Commercial products seem to use a lot of voice coil motors.

The first filter 62 and the second filter 63 may be fixed to the support frame 65 , and may be moved together with the support frame 65 . The first filter 62 and the second filter 65 may be arranged side by side. When the support frame 65 is slid left and right, any one of the first filter 62 and the second filter 63 may be disposed to cover the through-holes 61a and 61b, and the through-holes 61a and 61b It can filter the passing light.

The first filter 62 may include an optical filter 62 that selectively transmits only the second wavelength, which is the wavelength of fluorescence. The optical filter may selectively transmit light of a predetermined wavelength band including the second wavelength. Optical filter 62 can selectively transmit only approximately 610 nm wavelength. The first filter 62 may remove the excitation light emitted from the strip portion 10 and may improve the visibility of the fluorescent particles P for fluorescence.

The second filter 63 may include an IR cut filter. The IR cut filter 63 may remove a wavelength of an infrared region among light passing through the second filter 63 toward the sensing unit 30 . In this case, infrared may mean electromagnetic waves exceeding 700 nm and less than 1 mm. The second filter 63 may minimize the color shift phenomenon by removing red light that may be generated by infrared rays.

The optical measurement system 1 may be operated in a fluorescence detection mode or a visible light detection mode according to a user command input through the input unit 51 . The fluorescence detection mode and the visible light detection mode can be switched interchangeably.

In the fluorescence detection mode, the control unit 40 may repeat an on mode and an off mode of the first light source unit 21 . That is, in the fluorescence detection mode, the control unit 40 may control the first light source unit 21 to blink repeatedly. According to the fluorescence detection method described above with reference to FIGS. 3 to 5 , the fluorescence detection of the fluorescent particle-analyzed object conjugate 250 is possible.

The controller 40 may control the actuator 67 so that the filter body 66 slides so that the first filter 62 covers the through holes 61a and 61b.

The controller 40 may perform image processing of the signal received from the sensing unit 30 . For example, fluorescence detection of a fluorescent particle-analyzed object may be performed a plurality of times under the same conditions. The controller 40 may perform qualitative/quantitative analysis of the analyte from the fluorescence measurement values performed a plurality of times. Accordingly, the reliability of the qualitative/quantitative analysis of the analyte may be improved. In this case, the control unit 40 may adjust the exposure time (integration time), the frame (frame), and the gain (gain) of the sensing unit 30 . The controller 40 may convert the average value of the fluorescence measurement values performed a plurality of times into a signal and transmit it to the image display unit 50 . Accordingly, the image display unit 50 may display a fluorescence image that is clearer than the photographed fluorescence image.

In this specification, the exposure time (integration time) may mean a time for obtaining an image by opening the shutter of the sensing unit 30 . In the on mode, if the exposure time is increased, the measured light intensity and amount may be increased. According to an embodiment, in the off mode of the light source unit 20 , the shutter of the sensing unit 30 may be opened. Accordingly, the measured intensity and amount of light with respect to the exposure time may be relatively constant. Accordingly, the detection accuracy of the analyte may not be affected by the exposure time.

In the present specification, a frame may mean the number of cycles in which fluorescence is repeatedly measured under the same conditions. The on mode and the off mode of the light source unit 20 may be performed once per cycle, respectively. The gain value may be defined as a value that adjusts the analog-to-digital converter (ADC). When the gain value is increased, the contrast can be improved. Accordingly, detection accuracy may be improved.

According to the present invention, when the optical measurement system 1 is in the fluorescence detection mode, the on-mode duration, exposure time, frame, and gain value of the first light source unit 21 described above as well as delay time, image Conditions such as image sum, beginning mode, and total cut number can be optimized. For example, the fluorescence measurement may be performed multiple times. In this case, the start mode may mean each fluorescence measurement result, and the total number of cuts may mean the total number of fluorescence measurements. The image sum may be an average value of fluorescence measurement results of start modes. By such optimization, it is possible to improve the detection sensitivity of the fluorescent particle-analyte conjugate. The parameters to be adjusted and optimized in the optical measurement system are not limited to these examples and may vary. For example, the arrangement of the detection region and the capture material included in the detection region may be adjusted according to the type of the fluorescent particle and the type of the analyte. In addition, the intensity of light provided by the first light source unit 21, the detection sensitivity of the sensing unit 30, and the signal amplification rate and the peak detection method of the control unit 40 are adjusted, so that the detection sensitivity of the optical measurement system is increased. can be improved

In the visible light detection mode, the control unit 40 may control the second light source unit 22 to be in an on mode. That is, in the visible light detection mode, the control unit 40 may keep the second light source unit 22 turned on while there is no additional command.

The controller 40 may control the actuator 67 so that the filter body 66 slides so that the second filter 63 covers the through-holes 61a and 61b.

The controller 40 may perform image processing of the signal received from the sensing unit 30 . For example, the visible light detection of the fluorescent particle-analyzed object may be performed a plurality of times under the same conditions. The controller 40 may perform a qualitative/quantitative analysis of the analysis target from the visible light measurement values performed a plurality of times. Accordingly, the reliability of the qualitative/quantitative analysis of the analyte may be improved. In this case, the control unit 40 may adjust the exposure time (integration time), the frame (frame), and the gain (gain) of the sensing unit 30 . The control unit 40 may convert the average value of the visible light measurement values performed a plurality of times into a signal and transmit it to the image display unit 50 .

The input unit 51 may perform a function of inputting a signal to the control unit 40 . As an example, the input unit 51 may include a keyboard and/or a touch screen. The external device 53 may input a signal to the control unit 40 or may output a signal received from the control unit 40 . The external device 53 may include a printer and/or a barcode reader.

The image display unit 50 may receive the data processed by the controller 40 as an image signal, and display the analysis values of fluorescence as an image. The image display unit 50 may include an LED and/or an LCD.

9 to 11 show images displayed on an image display unit according to embodiments of the present invention. Hereinafter, it will be described with reference to FIG. 6 together.

9 , when the first light source unit 21 is in the OFF mode in the fluorescence detection mode, the plane of the strip unit 10 photographed may appear on the image display unit 50 . 10 and 11 , the fluorescence detection result analyzed by the controller 40 may be displayed. 10 is a graph showing the fluorescence detection result analyzed by the controller 40 according to an example. 11 is an example in which the fluorescence detection result analyzed by the controller 40 is displayed in a table. As another example, the image display unit 50 may display two or more images from FIGS. 9 to 11 . The image displayed on the image display unit 50 is not limited thereto and may vary.

12 is a perspective view illustrating a filter converter according to another embodiment in the optical measurement system shown in FIG. 6 . Fig. 13 is a side cross-sectional view of the filter converter shown in Fig. 12; FIG. 14 is a view showing the filter body shown in FIG. 13 . A description of overlapping parts will be omitted.

12 to 14 , the filter converter 60-1 includes a housing 61 having an internal space 61c and through-holes 61a and 61b formed therein, and a filter disposed inside the housing 61 . An actuator 67 for sliding the sieve 70 and the filter body 70 may be included. The filter body 70 may include a filter 712 that filters light passing through the through holes 61a and 61b, and a support frame 711 in which the filter 712 is disposed. The support frame 711 may extend to surround the edge of the filter 712 , and the filter 712 may be fixed to the support frame 712 .

The filter body 70 may include a plurality of filter bodies 70 . The plurality of filter bodies 70 may include a first filter body 71 and a second filter body 72 . The plurality of filter bodies 70 may further include a third filter body 73 . On the other hand, each of the filters and support frames of the first to third filter bodies 71 , 72 , and 73 may be described by attaching ordinal numbers such as “first” and “second”, respectively. In addition, the plurality of filter bodies 70 may include four or more filter bodies, and may be described to be distinguished from each other by attaching an ordinal number. Hereinafter, the structure of the first filter body 71 will be described as an example, but this description may be applied to other filter bodies as they are. The difference between the plurality of filter bodies may be only the type of filter.

The first filter body 71 may include a first filter 712 and a first support frame 711 . The second filter body 72 may include a second filter and a second support frame. The first filter 712 may include an optical filter that selectively transmits only the second wavelength, which is the wavelength of fluorescence. The optical filter may selectively transmit light of a predetermined wavelength band including the second wavelength. The optical filter 712 can selectively transmit only about 610 nm wavelength. The first filter 712 may improve the visibility of fluorescence by removing the excitation light emitted from the strip part. The second filter may include an IR cut filter. The IR cut filter may remove a wavelength in the infrared region among light passing through the second filter toward the sensing unit. In this case, infrared may mean electromagnetic waves exceeding 700 nm and less than 1 mm. The second filter may minimize the color shift phenomenon by removing red light that may be generated by infrared rays.

One end 61b of the through-holes 61a and 61b may be opened toward the strip portion 10 , and the other end 61a of the through-holes 61a and 61b may be opened toward the sensing unit 30 . Accordingly, light emitted from the strip unit 10 may pass through the through holes 61a and 61b to reach the sensing unit 30 . The through holes 61a and 61b may communicate with the inner space 61c of the housing 61 .

The inner space 61c of the housing 61 directly communicates with the through-holes 61a and 61b and includes an exposed area 61ca exposed to the outside by the through-holes 61a and 61b, and the through-holes 61a and 61b. It may include a shielding area 61cb that is not directly communicated with and is not exposed to the outside. The exposed area 61ca and the shielding area 61cb may be connected in a horizontal direction. As the filter bodies 71 and 72 disposed in the inner space 61c are slidably moved by the actuator 67, they may be moved to the exposed area 61ca or to the shielding area 61cb.

The filter body 70 may have a substantially rectangular flat plate shape disposed horizontally. The plurality of filter bodies 70 may be arranged in the vertical direction. The first filter body 71 and the second filter body 72 may be parallel to each other, and the second filter body 72 may be disposed above the first filter body 71 .

The actuator 67 may be disposed in the inner space 61c (eg, the shielding area 61cb). The actuator 67 may include a plurality of actuators 67 . The plurality of actuators 67 includes first actuators 67aa, 671a, and 672 for sliding any one of the first filter body 71 and the second filter body 72, and a second actuator 67ab for sliding the other one. ,671b). The second actuators 67ab and 671b may be disposed above the first actuators 67aa, 671a, and 672.

Either one of the first filter body 71 and the second filter body 72 is moved to the exposed area 61ca by the actuator 67 and exposed to the outside by the through-holes 61a and 61b, and the through-hole 61a . For example, as the first filter body 71 moves to the exposed area 61ca, the second filter body 72 may move to the shielding area 61cb, and the second filter body 72 moves to the exposed area 61ca. While moving to 61ca, the first filter body 71 may be moved to the shielding area 61cb.

The actuator 67 may be controlled by the control unit 40 similarly to the filter changer 60 shown in FIGS. 7 to 8 . In the fluorescence detection mode, the controller 40 may control the actuator 67 so that the first filter body 71 (or the first filter) covers the through holes 61a and 61b. In the visible light detection mode, the controller 40 may control the actuator so that the second filter body 72 (or the second filter) covers the through holes 61a and 61b.

The actuator 67 is coupled to the motors 67aa and 67ab, the pinions 671a and 671b driven by the motors 67aa and 67ab, and the pinions 671a and 671b and is fixed to the side end of the support frame 711. A rack 672 may be included. The actuator 67 may slide the filter body (or support frame) in a horizontal direction. The motor 67aa, the pinion 671a, and the rack 672 of the first actuators 67aa, 671a, and 672 may be referred to as a first motor, a first pinion, and a first rack, respectively, and the second actuator 67ab, The motor 67ab, the pinion 671b, and the rack of 671b may be referred to as a second motor, a second pinion, and a second rack, respectively. Meanwhile, the rack fixed to the side end of the third filter body 73 may be referred to as a third rack.

The filter converter 60 - 1 may include a guide rail 68 for guiding the movement of the filter body (or support frame). The guide rail 68 may extend in a horizontal direction. The guide rail 68 may be disposed in the shielding area 61cb. The guide rail 68 may be formed on the inner surface of the housing 61 . The guide rail 68 forms the inner space 61c (eg, the shielding area 61cb) of the housing 61 , extends along the movement direction of the filter body 70 , and may be formed on both sides facing each other. .

The guide rail 68 may include a plurality of guide rails 68 . The plurality of guide rails includes a first guide rail 68a for guiding the movement of any one of the first filter body 71 and the second filter body 72, and a second guide rail for guiding the movement of the other filter body ( 68b). The second guide rail 68b may be disposed on the first guide rail 68a.

Each of the plurality of filter bodies 70 may include a slide coupling part 713 that protrudes from both ends of the support frame 711 and is inserted into the guide rail 68 to be slidably coupled.

On the other hand, the filter changer 60 - 1 is disposed on the upper portion of the housing 61 , and the remaining filter body 70 (eg, the third filter body 73 ) is not disposed in the inner space 61c of the housing 61 . ) may further include a container 80 that is accommodated and stored. A storage space 81 may be formed inside the container 80 . One side of the accommodation space 81 may be opened so that the filter body 70 flows in and out. The container 80 may be disposed above the shielding area 61cb of the housing 61 so as not to cover the through-holes 61a and 61b.

One end of the inner space 61c of the housing 61 may be opened to the outside of the housing, and the filter converter 60-1 is a cover capable of opening and closing one end (or "outlet inlet") of the opened housing 61 . (61d) may be further included. The cover 61d may open and close the outlet of the housing 61 .

Since the filter body 70 is detachably coupled to the guide rail 68 and the actuator 67, the user opens the cover 61d and inserts the filter body 70 through the inlet and outlet of the housing 61 into the housing ( 61) can be separated externally. For example, the user may separate the filter body 70 by holding the filter body 70 and pulling it out in the direction of exiting through the outlet.

The user may mount the filter body 70 desired to be used on the housing inner space 61c, and the unused filter body 70 may be stored in the container 80 . The user can easily replace the filter body of the housing inner space 61c and the filter body of the container accommodation space 81 .

The operation according to the embodiment of the present invention can be implemented as a computer-readable program or code on a computer-readable recording medium. The computer-readable recording medium includes all types of recording devices in which data readable by a computer system is stored. In addition, the computer-readable recording medium may be distributed in a network-connected computer system to store and execute computer-readable programs or codes in a distributed manner.

In addition, the computer-readable recording medium may include a hardware device specially configured to store and execute program instructions, such as ROM, RAM, and flash memory. The program instructions may include not only machine language codes such as those generated by a compiler, but also high-level language codes that can be executed by a computer using an interpreter or the like.

Although some aspects of the invention have been described in the context of an apparatus, it may also represent a description according to a corresponding method, wherein a block or apparatus corresponds to a method step or feature of a method step. Similarly, aspects described in the context of a method may also represent a corresponding block or item or a corresponding device feature. Some or all of the method steps may be performed by (or using) a hardware device such as, for example, a microprocessor, a programmable computer, or an electronic circuit. In some embodiments, one or more of the most important method steps may be performed by such an apparatus.

In embodiments, a programmable logic device (eg, a field programmable gate array) may be used to perform some or all of the functions of the methods described herein. In embodiments, the field programmable gate array may operate in conjunction with a microprocessor to perform one of the methods described herein. In general, the methods are preferably performed by some hardware device.

Although the above has been described with reference to the preferred embodiment of the present invention, those skilled in the art can variously modify and change the present invention within the scope without departing from the spirit and scope of the present invention as described in the claims below. You will understand that it can be done.

One; optical measuring system
10; strip part
20; light source
30; sensing unit
40; control
50; video display

Claims (5)

An optical measurement system supporting a fluorescence detection mode for performing time-division fluorescence measurement and a visible light detection mode for performing visible light measurement, the optical measurement system comprising:
a strip unit in which a fluorescent particle-analysis object combination body formed by combining fluorescent particles absorbing light of a first wavelength and emitting light of a second wavelength to an analyte;
a light source unit including a first light source unit capable of irradiating light in a wavelength band including a first wavelength to the strip unit, and a second light source unit capable of irradiating light in a visible light wavelength band to the strip unit; and
a sensing unit provided to detect light or visible light of a second wavelength emitted from the strip unit;
A filter converter including a plurality of filters provided to filter light emitted from the strip unit and incident to the sensing unit, a filter converter selectively exposing any one of the plurality of filters to the outside; further comprising,
Further comprising; a control unit capable of controlling the light source unit and the filter changer;
The plurality of filters,
a first filter selectively transmitting a second wavelength; and
Including; a second filter for removing infrared wavelengths from the filtered light;
In the fluorescence measurement mode, the controller controls the first light source unit to repeat switching between the on mode and the off mode, controls the filter switch to expose the first filter to the outside, and the first light source unit is turned off. When controlling the sensing unit to detect the fluorescence emitted from the strip unit,
In the visible light measurement mode, the control unit controls the second light source to be in an on mode, and controls the filter switch to expose the second filter to the outside,
The filter converter,
a housing including an inner space and a through hole communicating with the inner space;
a first filter body including the first filter disposed inside the housing and a first support frame for fixing the first filter; and
a second filter body including the second filter disposed inside the housing and a second support frame for fixing the second filter;
The inner space includes an exposed area exposed to the outside by the through hole and a shielding area not exposed to the outside, wherein the first filter body and the second filter body are arranged side by side in a vertical direction,
The filter converter,
a first actuator disposed in the shielding area to slide the first filter body to the exposed area or the shielding area;
a second actuator disposed in the shielding area to slide the second filter body to the exposed area or the shielding area;
a first guide rail disposed in the shielding area to guide movement of the first filter body; and
A second guide rail disposed in the shielding area to guide the movement of the second filter body;
The first filter body further includes a first slide coupling part protruding from both ends of the first support frame and inserted into the first guide rail and slidably coupled to the first guide rail, wherein the second filter body includes the second filter body. 2 A second slide coupling part protruding from both ends of the support frame and inserted into the second guide rail to be slidably coupled; further comprising;
The first actuator includes a first motor, a first pinion driven by the first motor, and a first rack meshed with the first pinion and fixed to a side end of the first support frame, the second actuator comprising: A second motor, a second pinion driven by the second motor, and a second rack meshed with the second pinion and fixed to a side end of the second support frame,
The filter changer further includes a container disposed on the housing and storing an extra filter body that is not disposed in the inner space, wherein the container has a storage space in which the extra filter body is accommodated, , the receiving space has a structure in which one side can be opened so that the extra filter body flows in and out, the container is disposed above the shielding area so as not to cover the through hole, and the inner space has one end openable to the outside of the housing have a structure,
The first filter body is detachably coupled to the first guide rail and the first actuator, and the second filter body is detachably coupled to the second guide rail and the second actuator.
delete delete According to claim 1,
The strip part,
Board;
a developing film disposed on the substrate;
a sample pad disposed on the development layer and on which an analyte is disposed;
an emission pad disposed on the developing film and onto which fluorescent particles are adsorbed; and
and a detection region formed on the developing film, in which a capture material capable of binding to an analyte portion of the fluorescent particle-analyte complex is disposed;
The analyte of the sample pad flows through the developing film to combine with the fluorescent particles of the emission pad to form a fluorescent particle-analyzed complex;
The fluorescent particle-analysis target complex flows through the developing film to reach the detection area,
The light source unit irradiates light to the detection area to which the fluorescent particle-analysis target conjugate is fixed by the capture material, and the sensing unit measures light emitted from the detection area.
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