WO2022164176A1

WO2022164176A1 - Optical signal detection device

Info

Publication number: WO2022164176A1
Application number: PCT/KR2022/001312
Authority: WO
Inventors: Jin Won Kim; Jin Seok Noh; Soon Joo Hwang; Dong Woo Kang; Sang Min Kim; Seung Min Baik
Original assignee: Seegene, Inc.
Priority date: 2021-01-26
Filing date: 2022-01-25
Publication date: 2022-08-04
Also published as: KR20230132840A

Abstract

The disclosure relates to an optical signal detection device for analyzing a sample, which may precisely detect an optical signal by reducing noise caused as excitation light reflected by a blocking unit reaches a detector, wherein the blocking unit comprises a noise-reducing structure for adjusting a reflection angle of reflected light of the excitation light traveling along the second light path which is directed from a beam splitter to the blocking unit.

Description

OPTICAL SIGNAL DETECTION DEVICE

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

Nucleic acid amplification reaction well known as polymerase chain reaction (PCR) includes repeated cycles of double-stranded DNA denaturation, annealing of the oligonucleotide primers to DNA templates, and extension/elongation of the primers with the DNA polymerase (Mullis et al., U.S. Patent Nos. 4,683,195, 4,683,202, and 4,800,159; Saiki et al., (1985) Science 230, 1350-1354). DNA denaturation is performed at about 95 ℃, and annealing and primer elongation are performed at a lower temperature ranging from 55 ℃ to 75 ℃.

The light source emits excitation light to the samples, and the fluorescent material contained therein, excited by the excitation light, emits fluorescence. A detector is configured to detect the emission light emitted from the fluorescent material and analyzes the amplification reaction. In such a fluorescence detection-type device, it is necessary to accurately provide excitation light to the sample and accurately provide emission light to the detector.

The emission light emitted from the sample is guided to the detector by a beam splitter. The excitation light emitted from the light source may pass through the beam splitter to the sample, and the emission light emitted from the sample is reflected by the beam splitter to the detector.

In the above-described configuration, among the excitation light emitted from the light source, the light reflected by the beam splitter is re-reflected to reach the detector, causing noise in some cases. As illustrated in FIG. 1, in a case where a light path for excitation light and emission light is provided, and a blocking unit for blocking external light is configured, some of the excitation light may reach the detector, causing noise. More specifically, when the excitation light emitted from the light source 11 passes through the beam splitter 12 and reaches the sample 10 as shown in FIG. 1(a), some of the excitation light, after reflected by the beam splitter 12 and re-reflected by an inner surface of the blocking unit 14, may pass through the beam splitter 12 and reach the detector 13. Or, when the excitation light emitted from the light source 11 is reflected by the beam splitter 12 and reaches the sample 10 as shown in FIG. 1(b), some of the excitation light may pass through the beam splitter 12 and, after transmitted through the beam splitter 12 and reflected on the inner surface of the blocking unit 14, reach the detector 13. Therefore, to accurately detect the optical signal generated from the sample, it is required to reduce the excitation light reaching the detector from the light source as described above.

In the above-described background, the inventors of the instant application have tried to develop a new optical signal detection technology capable of reducing noise caused when excitation light emitted from a light source is introduced into a detector. As a result, the inventors has developed an optical signal detection device capable of reducing noise by forming a blocking module including a blocking unit disposed along the path of excitation light and adjusting the reflection angle of the excitation light reflected by the blocking unit, which reaches the blocking unit from a beam splitter.

Thus, an objective of the present disclosure is to provide an optical signal detection device including a noise-reducing structure for adjusting the reflection angle of reflected light of an excitation light reaching the blocking unit from the beam splitter, as a device for analyzing the sample received in the sample holder.

To achieve the foregoing objects, according to the disclosure, there is provided a device for detecting an optical signal to analyze a sample received in a sample holder comprising a light source module comprising a light source unit configured to irradiate excitation light to the sample holder, a detection module comprising a detection unit configured to detect emission light from the sample holder, and a blocking module comprising a blocking unit receiving a beam splitter and accommodating a path of the excitation light defined by the beam splitter, wherein the path of the excitation light comprises a first light path directed from the beam splitter to the sample holder and a second light path directed from the beam splitter to the blocking unit, and wherein the blocking unit comprises a noise-reducing structure for adjusting a reflection angle of reflected light of the excitation light traveling along the second light path and being reflected from the blocking unit to reduce the amount of the reflected light of the excitation light directed toward the detection module.

According to the disclosure, it is possible to accurately detect an optical signal by reducing noise generated when the excitation light reflected by the blocking unit reaches the detector.

According to the disclosure, it is also possible to prevent inter-light interference and reduce noise generated when the excitation light emitted from a plurality of light source units is reflected and reaches a plurality of detectors in a case where excitation light is irradiated to a plurality of samples from the plurality of light source units, and emission light emitted from the plurality of samples is detected.

FIG. 1 is a side view illustrating a conventional optical signal detection device;

FIG. 2 is a side view illustrating an optical signal detection device according to an embodiment of the disclosure;

FIGS. 3, 4, and 5 are side views illustrating an optical signal detection device according to an embodiment of the disclosure;

FIG. 6 is a side view illustrating an optical signal detection device according to an embodiment of the disclosure; and

FIG. 7 is a perspective view illustrating a portion of an optical signal detection device according to an embodiment of the disclosure.

The configuration and effects of the disclosure are now described in further detail in connection with embodiments thereof. The embodiments are provided merely to specifically describe the disclosure, and it is obvious to one of ordinary skill in the art that the scope of the disclosure is not limited to the embodiments.

Such denotations as "first," "second," "A," "B," "(a)," and "(b)," may be used in describing the components of the disclosure. These denotations are provided merely to distinguish a component from another, and the essence of the components is not limited by the denotations in light of order or sequence. When a component is described as "connected," "coupled," or "linked" to another component, the component may be directly connected or linked to the other component, but it should also be appreciated that other components may be "connected," "coupled," or "linked" between the components.

FIG. 2 is a side view illustrating an optical signal detection device 100 according to an embodiment of the disclosure. According to the disclosure, an optical signal detection device 100 detects an optical signal generated from a sample to analyze the sample received in a sample holder 20.

The optical signal generated from the sample may be, e.g., an optical signal that is generated depending on the properties of the target analyte, such as activity, amount, or presence (or absence), specifically presence (or absence). The magnitude or change of the optical signal serves as an indicator qualitatively or quantitatively indicating the properties, specifically the presence or absence, of the target analyte. The target analyte may be, e.g., a target nucleic acid sequence or a target nucleic acid molecule including the same. Thus, the optical signal detection device 100 according to the disclosure may be a target nucleic acid sequence detection device.

Referring to FIG. 2, the optical signal detection device 100 of the disclosure includes a light source module 110, a detection module 120, and a blocking module 130. The blocking module 130 comprises a beam splitter 140 for guiding the emission light emitted from the sample holder 20 to the detection module 120. The blocking unit 130 includes a noise-reducing structure 150 for adjusting the reflection angle of reflected light of the excitation light emitted from the light source module 110 and reflected by the beam splitter 140 to reduce the amount of the reflected light of the excitation light directed toward the detection module 120.

The light source module 110 according to the disclosure supplies an appropriate optical stimulus to the sample received in the sample holder 20, and the detection module 120 detects an optical signal generated from the sample in reaction to the optical stimulus.

The optical signal may be luminescence, phosphorescence, chemiluminescence, fluorescence, polarized fluorescence, or other colored signal. The optical signal may be an optical signal generated in response to an optical stimulus applied to the sample.

The sample holder 20 receives a sample. All the substances that are received in the optical signal detection device 100 of the disclosure and are subject to optical signal detection reaction are included in samples of the disclosure.

The sample holder 20 is configured to directly receive the sample or to receive a reaction vessel containing the sample. The reaction vessel includes a reaction vessel that may contain one sample and reaction vessels that may separately contain a plurality of samples.

The sample holder 20 may be an electrically conductive material. The sample holder 20 may be configured such that, when the sample or reaction vessel is received, heat may be transferred from the sample holder 20 to the sample or the reaction vessels. For example, the sample holder 20 may include a conductive metal, such as aluminum, gold, silver, nickel, or copper. Alternatively, a separate component from the sample holder 20 may be provided to control the temperature of the samples in the reaction vessel by directly supply energy to the sample or the reaction vessel. In this case, the sample holder 20 may be configured to accommodate the reaction vessels but not to transfer heat to the reaction vessels.

An example of the sample holder 20 is a heating block. The heating block may include a plurality of holes, and reaction vessels may be positioned in the holes, respectively.

Another example of the sample holder 20 is a heating plate. The heating plate may be configured such that a thin metal sheet attached to the plate receiving the sample. The heating plate may be operated in such a manner that the plate is heated by applying electric current to the thin metal sheet.

Another example of the sample holder 20 is a receiving unit capable of receiving one or more chips or cartridges. An example of the cartridge is a fluid cartridge including a flow channel.

The sample holder 20 is configured to accommodate a plurality of samples and a reaction for detecting a nucleic acid such as a nucleic acid amplification reaction can proceed by controlling the temperature of the plurality of samples. For example, when the sample holder 20 is a heating block with a plurality of wells, the sample holder 20 is configured as a single heating block, and all of the wells of the heating block may be configured not to be thermally independent from each other. In this case, the temperatures of all the wells in which samples are received in the sample holder 20 are the same, and the temperature of the received samples may not be adjusted according to different protocols.

As another example, the sample holder 20 may be configured to control the temperature of some of the samples received in the sample holder according to different protocols. In other words, the sample holder 20 may include two or more thermally independent reaction areas. The reaction areas are thermally independent from each other. Heat is not transferred from one reaction area to another. For example, an insulating material or air gap may be present between the reaction areas. The temperature of each reaction area may be controlled independently. An individual reaction protocol including temperature and time may be set for each reaction area. Each reaction area may perform reaction by an independent protocol. Since reaction is performed in the reaction areas according to independent protocols, the time points of light detection in the reaction areas are independent of each other.

The sample holder 20 positions the sample in a predetermined position so that the optical stimulus reaches the sample and the optical signal generated from the sample reaches the detection module 200. The sample holder 20 may also perform a process for detecting an optical signal from the sample, such as temperature control of the sample.

The light source module 110 includes a light source unit 111 configured to irradiate excitation light to the sample holder 20 which contains the sample. The light source module 110 may include a filter unit 112 that filters the light emitted from the light source unit 111.

The light source module 110 emits light to excite the optical label included in the sample. The light emitted from the light source unit 111 of the light source module 110 may be denoted as excitation light. The light emitted from the sample may be denoted as emission light. The path of the excitation light from each light source unit 111 may be referred to as an excitation light path. The path of the emission light from the sample may be referred to as an emission light path. The light source unit 111 and the detection unit 121 may be disposed in fixed positions with respect to the sample holder 20 to maintain an accurate light path.

The light source unit 111 may include a light source element (not shown). One light source unit 111 may include one or more light source elements. For example, the light source element may be a light emitting diode (LED), including an organic LED, inorganic LED, and quantum dot LED, or a laser unit including a tunable laser, He-Ne laser, or Ar laser. According to an embodiment, the light source element may be an LED.

The filter unit 112 filters the light emitted from the light source unit 111 so that light of a specific wavelength range reaches the sample. The filter unit 112 includes one or more filters.

The filter unit 112 filters the light emitted from the light source unit 111. Filtration means selectively transmitting or blocking a specific wavelength range of light of the light emitted from the light source unit 111. Selectively transmitting means transmitting 50%, 60%, 70%, 80%, or 90% or more of the amount of light in the desired wavelength range. Selectively blocking means blocking 50%, 60%, 70%, 80%, or 90% or more of the amount of light in the desired wavelength range.

The filter unit 112 of the disclosure selectively transmits a specific wavelength range of light of the light emitted from the light source unit 111 to the sample. Thus, among the optical labels included in the sample, only a specific optical label generates an optical signal.

A plurality of filter units 112 may be provided. Each filter unit includes a filter and transmits light in a wavelength range capable of exciting at least one of the optical labels.

The filter included in the filter unit 112 of the disclosure may be a bandpass filter. The bandpass filter refers to a filter that selectively transmits a certain wavelength range of light. The wavelength range of light transmitted through the bandpass filter is referred to as the passband of the filter. The passband may be represented in the form of a wavelength range. A filter including a specific passband means a filter that transmits light of a wavelength included in the specific passband. For example, the plurality of filter units may include a filter unit including a filter of a first passband and a filter unit including a filter of a second passband. The first pass band and the second pass band each may include a wavelength region of light capable of exciting a specific optical label. In particular, the optical label may be selected from the group consisting of FAM, CAL Fluor Red 610, HEX, Quasar 670, and Quasar 705. Each of the plurality of filter units 112 may pass light capable of exciting a different optical label.

Accordingly, according to an embodiment of the disclosure, the respective pass bands of the plurality of filter units may not overlap each other. Each of the filter units may be disposed to selectively excite a different optical label. Accordingly, according to an embodiment of the disclosure, the pass bands of the filter units may differ from each other.

According to an embodiment of the disclosure, the optical signal detection device 100 of the disclosure may include a moving means (not shown) capable of moving the plurality of filter units. The moving means may include, e.g., a motor. The motor may be, e.g., an AC motor, a DC motor, a step motor, a servo motor, or a linear motor, and may preferably be a step motor. The filter unit may be alternately disposed on the light source 111 by the moving means.

The detection module 120 detects an optical signal. The detection module 120 detects fluorescence, which is an optical signal generated from the sample.

The detection module 120 includes a detection unit 121 configured to detect emission light emitted from the sample holder 20 in which the sample is placed. The detection module 120 includes a filter unit 122 that filters the emission light emitted from the sample holder 20. The detection unit 121 includes a detector that detects light.

The detection unit 121 may detect the optical signal by generating an electrical signal according to the intensity of the optical signal. The detection unit 121 is configured to detect the emission light emitted from the optical label included in the sample. The detection unit 121 may sense the amount of light per wavelength distinctively for light wavelengths or may sense the total amount of light regardless of wavelengths. Specifically, the detection unit 121 may use, e.g., a photodiode, a photodiode array, a photo multiplier tube (PMT), a charge-coupled device (CCD) image sensor, a complementary metal-oxide-semiconductor (CMOS) image sensor, or an avalanche photodiode (APD).

The filter unit 122 filters the light emitted from the sample holder 20 so that light of a specific wavelength range reaches the detection unit 121. The filter unit 122 includes one or more filters.

A plurality of filter units 122 may be provided and may be switched depending on the wavelength of the emission light so that a different filter unit 122 filters the emission light. The filter of the filter unit 122 is a filter for selectively transmitting the emission light emitted from the optical label included in the sample. When the detection unit 121 detects light of a wavelength range other than the emission light emitted from the optical label included in the sample, the optical signal may not be accurately detected. The filter of the filter unit 122 enables the target to be accurately detected by selectively passing the emission light emitted from the optical label.

The beam splitter 140 reflects and transmits the light incident from the light source unit 111, and the beam splitter 140 reflects and transmits the emission light emitted from the sample. Accordingly, the excitation light from the light source unit 111 reaches the sample holder 20, and the emission light from the sample holder 20 reaches the detection unit 121.

FIG. 2 illustrates an embodiment of the disclosure in which the light source unit 111 and the sample holder 20 are disposed to face each other. According to the embodiment, the light irradiated from the light source unit 111 may pass through the beam splitter 140 and reach the sample holder 20, and the light emitted from the sample holder 20 may be reflected by the beam splitter 140 and reach the detection unit 121. Although not shown in the drawings, according to another embodiment of the disclosure, the detection unit 121 and the sample holder 20 may be disposed to face each other so that the light irradiated from the light source unit 111 is reflected by the beam splitter 140 and reaches the sample holder 20, and the light emitted from the sample holder 20 may pass through the beam splitter 140 and reach the detection unit 121. In all of the above-described embodiments, the excitation light split by the beam splitter 140 forms a first light path 21 directed from the beam splitter 140 to the sample holder 10 and a second light path 22 directed from the beam splitter 140 to the blocking unit 131. The second light path 22 is a light path along which the light on the second light path 22 may be reflected by the blocking unit 131 and transmitted through the beam splitter 140 or may be reflected by the beam splitter 140 and then reach the detection unit 121.

The blocking module 130 includes a blocking unit 131 that comprises the beam splitter 140 and accommodates the path of the excitation light defined by the beam splitter 140. The blocking unit 131 may be disposed along the path of the excitation light and the path of the emission light. The blocking unit 131 is configured to form an internal space 132 accommodating the path of the excitation light. The internal space 132 may be determined by the path of the excitation light and the path of the emission light.

The blocking unit 131 allows the excitation light irradiated to the sample from the light source module 110 and the emission light emitted to the detection module 120 to pass through the internal space 132 of the blocking unit 131. In this case, the excitation light and the emission light may pass along the same path in some section of each internal space. Since emission light is emitted only when excitation light is irradiated, the excitation light and the emission light, although they do not pass through at the same time, may pass along the same path. When light is irradiated to the sample holder 20, emission light is emitted from the reaction site of the sample holder 20 irradiated with the light. Thus, the path of the emission light from the sample holder to the beam splitter received in the blocking unit 131 may be identical to the path of the excitation light irradiated to the sample.

According to the disclosure, path of excitation light refers to an area where the excitation light irradiated from the light source unit 111 passes, and path of emission light refers to an area where the emission light directed from the sample holder 20 to the detection unit 121 passes.

The path of excitation light includes a first light path 21 directed from the beam splitter 140 to the sample holder 20 and a second light path 22 directed from the beam splitter 140 to the blocking unit 131. The first light path 21 is a light path along which the excitation light reaches the sample holder 20 from the beam splitter 140, and the second light path 22 is a light path along which the excitation light reaches the blocking unit 131 from the beam splitter 140. After reaching the beam splitter 140 from the light source unit 111, the excitation light is split into the first light path 21 and the second light path 22. According to an embodiment, the light of the first light path 21 may be the excitation light passing through the beam splitter 140, and the light of the second light path 22 may be the excitation light reflected by the beam splitter 140. According to another embodiment, the light of the first light path 21 may be the excitation light reflected by the beam splitter 140, and the light of the second light path 22 may be the excitation light transmitted through the beam splitter 140.

The blocking unit 131 includes an opening 133 to the light source unit 111, an opening 135 to the sample holder 20, and an opening 134 to the detection unit 121. Excitation light is irradiated from the light source unit 111 through the

openings

133, 134, and 135 and the internal space 132 and reaches the sample holder 20, and emission light is emitted from the sample holder 20 and reaches the detection unit 121.

The blocking unit 131 includes a noise-reducing structure 150 that adjusts the reflection angle of the reflected light of the excitation light traveling along the second light path and being reflected from the blocking unit to reduce the amount of the reflected light of the excitation light directed toward the detection module 120.

The light of the second light path 22 reaching the blocking unit 131 may be absorbed and blocked by the blocking unit 131, and the noise-reducing structure 150 may reduce the amount of the reflected light directed toward the detection module 120 wherein the reflected light is reflected, rather than absorbed, by the blocking unit 131 and enhance noise performance. The noise-reducing structure 150 reduces the amount of light directed toward the detection module 120 wherein the light is reflected by the blocking unit 131 and is transmitted through or reflected by the beam splitter 140. Thus, the noise-reducing structure 150 may be positioned to face the beam splitter 140. If the noise-reducing structure 150 is not included as in the conventional device discussed above in connection with FIG. 1, the light of the second light path 22 reflected on the inner surface of the blocking unit 151 may be transmitted through or reflected by the beam splitter 140 and reach the detection unit 121. According to an embodiment, the noise-reducing structure 150 may be positioned on the opposite side of the opening 134 facing the detection unit 121, with the beam splitter 140 disposed therebetween. According to another embodiment, the noise-reducing structure 150 may be positioned on the opposite side of the opening 133 facing the light source unit 111, with the beam splitter 140 disposed therebetween.

Referring Figs. 1 and 2, the reflected light of the second light path 22 is reflected from the blocking unit 131 and to the opposite direction parallel to the incident direction and directed toward the detection module by being transmitted through or reflected by the beam splitter 140. Referring to the embodiment shown in FIG. 2, the reflection angle of the reflected light may be adjusted not to be parallel to the incident direction so as to reduce the amount of the reflected light directed toward the detection module 120.

According to an embodiment of the disclosure, the noise-reducing structure 150 may reflect the light of the second light path 22 in a direction inclined with respect to the incident direction. As shown in Figs. 2 and 3, the reflected light may be reflected to be directed to an upper or lower side of the incident direction by the noise-reducing structure 150 so that the amount of reflected light arriving at the detection module 120 may reduce. The direction in which the reflection angle of the reflected light is adjusted is not limited, and the reflected light may be reflected to a left or right side of the incident direction.

Thus, the noise generated by the light of the second light path 22, which does not reach the sample holder but is reflected by the blocking unit 131, may be reduced by the noise-reducing structure 150. Further, the detection module 120 may accurately detect the emission light emitted from the sample holder 20.

As described above, the blocking unit 131 is configured to form the internal space 132 accommodating the path of excitation light, and the noise-reducing structure 150 may include a contact surface 151 for the second light path 22 positioned on an inner surface of the blocking unit 131. In other words, the light of the second light path 22 reaches the contact surface of the blocking unit 131. The contact surface 151 is configured as an inner surface of the blocking unit 131 forming the internal space 132. The light of the second light path 22 reaches and is reflected on the contact surface 151, and the reflected light is reflected in a direction inclined with respect to the incident direction.

The noise-reducing structure may be positioned on an area of the blocking unit 131 where the second light path reaches. The contact surface 151 may be the area of the blocking unit 131 where the second light path reaches.

The contact surface 151 may be configured so that the light of the second light path 22 is reflected in two or more different directions. For example, the contact surface 151 may be configured so that the reflected light is reflected to an upper and lower side or a left and right side with respect to the incident direction of the light of the second light path 22.

The contact surface 151 is configured in the surface facing the beam splitter 140 in an inner surface of the blocking unit 131. In other words, the contact surface 151 may be positioned on the opposite side of the opening 134 with the beam splitter 140 disposed therebetween. Thus, the light of the second light path 22, which directed from the beam splitter 140 to the blocking unit 131, reaches the contact surface 151.

Preferably, the contact surface 151 may have a large area to increase the amount of the reflected light whose reflection angle is adjusted. For example, the contact surface 151 may have a larger area than the opening 134 to the detection module 120 configured in the blocking unit 131. As the amount of the reflected light whose reflection angle is adjusted by the contact surface 151 increases, the reflected light reaching the detection module 120 reduces.

At least a portion of the contact surface 151 may be configured not to be perpendicular to the second light path 22. In other words, at least a portion of the contact surface 151 is configured not to be perpendicular to the direction in which the light of the second light path 22 is incident, so that the reflected light reflected on the at least a portion of the contact surface 151 is reflected in a direction not parallel to the incident direction, and the amount of the reflected light directed toward the detection module 120 is reduced. The contact surface 151 may be configured to be inclined with respect to a direction perpendicular to the second light path 22.

Referring to FIG. 3, the contact surface 151 may be configured as an inner surface of the blocking unit 131 inclined. As the contact surface 151 is configured to be inclined, the light of the second light path 22 reaching the contact surface 151 is reflected to be inclined with respect to the incident direction. In other words, the reflection angle of the reflected light is adjusted depending on the degree of inclination of the contact surface 151.

The contact surface 151 may be configured to obliquely protrude or be depressed from the inner surface of the blocking unit 131. In other words, the contact surface 151 may protrude or be depressed in the incident direction of the light of the second light path 22 or in the opposite direction. The contact surface 151 may be formed to be inclined, with the depth at which the contact surface 151 protrudes or is depressed increasing in one direction. FIG. 3 illustrates an embodiment in which the protruding height of the contact surface 151 increases from a lower side to an upper side.

According to an embodiment, the contact surface 151 may be configured to be inclined, with the protruding height increasing from the lower side to the upper side. According to another embodiment, the contact surface 151 may be formed to be inclined, with the protruding height increasing from the upper side to the lower side. According to another embodiment, the contact surface 151 may be formed to be inclined, with the depressed depth increasing from the lower side to the upper side or from the upper side to the lower side. According to another embodiment, the contact surface 151 may be formed to be inclined, with the protruding height or depressed depth increasing to the left or right as viewed in the incident direction of the light of the second light path 22.

According to another embodiment, the contact surface 151 may protrude or be depressed to be inclined in two or more directions. For example, as shown in FIG. 4, the contact surface 151 may include both an inclined surface (refer to reference number 151a) that increases in height from the bottom to the top and an inclined surface (refer to reference number 151b) that increases in height from the top to the bottom. According to another embodiment, the contact surface 151 may include an inclinedly protruding portion and an inclinedly depressed portion. As the contact surface 151 includes a plurality of inclined surfaces, it is possible to reduce the height protruding from the inner surface of the blocking unit 131 while maintaining an area and inclined angle of the inclined surfaces. Accordingly, it is possible to prevent light required for optical signal detection from being blocked by the protruding contact surface 151. The light required for the optical signal detection that may be blocked may be a portion of the excitation light irradiated from the light source unit 111 and reaching the sample holder 20 in a device with a structure in which the light source unit faces the sample holder 20. The light required for the optical signal detection that may be blocked may be a portion of the emission light emitted from the sample holder 20 and reaching the detection unit 121 in a device with a structure in which the detection unit 121 faces the sample holder 20. According to another embodiment, the contact surface 151 may include a plurality of protruding and depressed structures. Each of the protruding and depressed structures may include an inclined surface to adjust the reflection angle of the reflected light.

Referring to FIG. 5, the noise-reducing structure 150 may be an inclined member 310 including the contact surface 151 and provided on an inner surface of the blocking unit 131. In other words, as shown in FIGS. 3 to 4, the noise-reducing structure 150 may be integrally configured on the inner surface of the blocking unit 131, or as shown in FIG. 5, the noise-reducing structure 150 may be configured separately from the blocking unit 131 and coupled to the inner surface of the blocking unit 131. The inclined member 310 may increase or decrease in thickness in one direction while forming an inclination of the contact surface 151 or may increase or decrease in thickness in two or more directions while forming an inclination of the contact surface 151.

The contact surface 151 that may be configured as described above may be configured so that the reflection angle of the reflected light with respect to the contact surface 151 is 10 degrees or more. To reduce noise at the detection module 120, it is preferable that the reflection angle of the reflected light be 10 degrees or more. Accordingly, the reflected light may be reflected at an angle of 20 degrees or more from the second light path 22. The reflection angle of the reflected light with respect to the contact surface 151 is not limited thereto, but may be, e.g., 10 degrees or more, 20 degrees or more, 30 degrees or more, 40 degrees or more, 45 degrees or more, 50 degrees or more, or 60 degrees or more. The reflection angle of the reflected light with respect to the contact surface 151 may be 90 degrees or less, 80 degrees or less, or 70 degrees or less. When the reflection angle of the reflected light with respect to the contact surface 151 is too high, the light required for optical signal detection may be blocked by the protruding contact surface 151. However, if a plurality of protruding structures are provided on the contact surface 151, it may be possible to prevent light from being blocked by the contact surface while securing a high reflection angle.

Referring to FIG. 6, the sample holder 20 may be divided into a plurality of sample areas. The light source module 110 may include a plurality of light source units 111. Each light source unit 111 may be configured to irradiate excitation light to its corresponding sample area. The detection module 120 may include a plurality of detection units 121. Each detection unit 121 may be configured to detect the emission light emitted from its corresponding sample area. The blocking module 130 may include a plurality of blocking units 131. Each blocking unit 131 may accommodates the path of the excitation light irradiated to its corresponding sample area.

Each sample area means an area on the sample holder 20 in which samples for which an optical signal detection reaction is performed by the same light source unit 111 are positioned. In other words, the sample area of the disclosure means a group of a plurality of reaction sites included in the sample holder 20. The sample area may be an area differentiated by the excitation light irradiation area of the light source unit 111.

When the sample holder 20 includes two or more thermally independent reaction areas, each sample area is not defined over two or more reaction areas but is included in one reaction area or may be defined as the same area as one reaction area. When the sample area is so defined, optical signal detection may be performed on the two or more thermally independent reaction areas by different light source units and filter units at an independent detection time. According to an embodiment of the disclosure, the sample holder 20 may include two or more reaction areas thermally independent from each other, and each sample area may be defined to be included in any one of the two or more reaction areas thermally independent from each other.

FIG. 6 illustrates an example in which the sample holder 20 is divided into two

sample areas

20a and 20b, but the sample holder 20 of the disclosure is not limited thereto. The sample holder of the disclosure may be a sample holder including, e.g., 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, or 24 sample areas.

The plurality of light source units 111 are configured to individually irradiate light to different sample areas. In other words, each light source unit 111 irradiates excitation light to an individually assigned sample area. The plurality of detection units 121 are configured to detect the emission light emitted from each assigned sample area among the plurality of sample areas of the sample holder 20. Each detection unit 121 may detect a plurality of signals generated in the assigned sample areas. Accordingly, a path of excitation light irradiated from each light source unit 111 and reaching a corresponding sample area is configured, and a path of emission light emitted from each sample area and reaching a corresponding detection unit 121 is configured.

When the plurality of light source units 111 individually irradiate excitation light to different sample areas, it is difficult for each light source unit 111 to maintain the same light path, causing an error. Further, when a plurality of light source units 111 simultaneously irradiate light to the plurality of sample areas, an issue with cross-talk may occur. For example, when each of the plurality of light source units 111 irradiates light to a different sample area, excitation light may be mixed between neighboring sample areas, or interference between the excitation light may occur, or light may be irradiated to a sample area other than the predetermined sample area. In this case, the light to be provided to a specific sample area cross-talks with the light irradiated to another area, so that the light is not correctly provided to the samples positioned in the predetermined sample area and accuracy is not ensured for the optical detection signal generated in reaction to light stimulation.

Thus, the blocking module 130 may include the plurality of blocking units 131 disposed in the respective sample areas along the path of the excitation light irradiated to each of the plurality of sample areas and the path of the emission light emitted from each of the plurality of sample areas.

The blocking module 130 according to the disclosure is configured to be positioned with respect to the excitation light path for each different sample area to prevent cross-talk due to mixture of excitation light between the neighboring sample areas when each of the plurality of light source units 111 irradiates light to a different sample area.

The noise-reducing structure 150 may be formed in each of the plurality of blocking units 131 to adjust the reflection angle of the reflected light so as to reduce the amount of the reflected light of the second light path 22 directed toward the detection module 120.

In other words, each of the plurality of blocking units 131 may include a noise-reducing structure 150 to reduce the amount of light directed toward the detection module 120, wherein the light irradiated from each light source unit to each blocking unit 131 by being reflected by or transmitted through the beam splitter 140. Thus, each noise-reducing structure 150 reduces the amount of the reflected light toward the detection unit 121 by reflecting the light of the second light path 22 in a direction inclined with respect to the incident direction. Each noise-reducing structure 150 includes a contact surface 151 for the second light path 22 positioned on an inner surface of each blocking unit 131. Each contact surface 151 may be configured as an inner surface of each blocking unit 131 is inclined, or an inclined member 310 including a contact surface 151 may be provided on an inner surface of each blocking unit 131.

FIG. 7 illustrates an embodiment in which a blocking module 130 includes six blocking units 131, and the contact surface 151 of each noise-reducing structure 150 protrudes obliquely. Each blocking unit 131 receives the beam splitter 140 and includes an opening 134 configured to face the corresponding detection unit 121. Each noise-reducing structure 150 may be positioned to face a corresponding opening 134. The position of the noise-reducing structure 150 may be changed depending on the direction in which the opening 134 is configured.

When an element "comprises," "includes," or "has" another element, the element may further include, but rather than excluding, the other element, and the terms "comprise," "include," and "have" should be appreciated as not excluding the possibility of presence or adding one or more features, numbers, steps, operations, elements, parts, or combinations thereof. All the scientific and technical terms as used herein may be the same in meaning as those commonly appreciated by a skilled artisan in the art unless defined otherwise. It will be further understood that terms, such as those defined dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

The above-described embodiments are merely examples, and it will be appreciated by one of ordinary skill in the art various changes may be made thereto without departing from the scope of the disclosure. Accordingly, the embodiments set forth herein are provided for illustrative purposes, but not to limit the scope of the disclosure, and should be appreciated that the scope of the disclosure is not limited by the embodiments. The scope of the disclosure should be construed by the following claims, and all technical spirits within equivalents thereof should be interpreted to belong to the scope of the disclosure.

While embodiments of the disclosure have been described above, it will be apparent to one of ordinary skill in the art that the above-described specific techniques are merely preferred embodiments and the scope of the disclosure is not limited thereto. Thus, the scope of the disclosure is defined by the appended claims and equivalents thereof.

[legend of Reference Numbers]

10: sample 11: light source

12: beam splitter 13: detector

14: blocking unit 20: sample holder

20a, 20b: sample areas 21: first light path

22: second light path 100: optical signal detection device

110: light source module 111: light source units

112: filter units 120: detection module

121: detection unit 122: filter unit

130: blocking module 131: blocking unit

132:

internal space

133, 134, 135: opening

140: beam splitter 150: noise-reducing structure

151: contact surface 310: inclined member

[CROSS-REFERENCE TO RELATED APPLICATION(S)]

This application claims priority to Korean Patent Application No. 10-2021-0010673, filed on January 26, 2021, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference in its entirety.

Claims

A device for detecting an optical signal to analyze a sample received in a sample holder, the device comprising:

a light source module comprising a light source unit configured to irradiate excitation light to the sample holder;

a detection module comprising a detection unit configured to detect emission light from the sample holder; and

a blocking module comprising a blocking unit comprising a beam splitter and accommodating a path of the excitation light defined by the beam splitter,

wherein the path of the excitation light comprises a first light path directed from the beam splitter to the sample holder and a second light path directed from the beam splitter to the blocking unit, and

wherein the blocking unit comprises a noise-reducing structure for adjusting a reflection angle of reflected light of the excitation light traveling along the second light path and being reflected from the blocking unit to reduce the amount of the reflected light of the excitation light directed toward the detection module.
The device of claim 1, wherein the sample holder is divided into a plurality of sample areas,

wherein the light source module comprises a plurality of light source units each of which is configured to irradiate excitation light to each sample area,

wherein the detection module comprises a plurality of detection units each of which is configured to detect emission light from each sample area, and

wherein the blocking module comprises a plurality of blocking units each of which accommodates the path of the excitation light irradiated to each sample area.
The device of claim 2, wherein each of the plurality of blocking units comprise the noise-reducing structure.
The device of claim 1, wherein the noise-reducing structure reflects the light of the second light path in a direction inclined with respect to a direction of incidence.
The device of claim 1, wherein the blocking unit is configured to form an internal space accommodating the path of the excitation light, and

wherein the noise-reducing structure comprises a contact surface for the second light path positioned on an inner surface of the blocking unit.
The device of claim 5, wherein the contact surface is configured as the inner surface of the blocking unit inclined.
The device of claim 6, wherein the contact surface is configured to obliquely protrude from the inner surface of the blocking unit or to be obliquely recessed.
The device of claim 5, wherein the noise-reducing structure is an inclined member comprising the contact surface and provided on the inner surface of the blocking unit.
The device of claim 5, wherein at least a portion of the contact surface is configured not to be perpendicular to the second light path.
The device of claim 5, wherein the contact surface is configured so that the reflection angle of the reflected light is 10 degrees or more with respect to the contact surface.