Optical imaging system and biomolecule detection system

Abstract

The embodiment of the invention provides an optical imaging system and a biomolecule detection system, the optical imaging system comprises a light source device and an imaging device, and the light source device is used for emitting exciting light to excite a to-be-detected sample to generate a plurality of optical signals of different wavebands. The imaging device comprises an objective lens, a multi-band-pass optical filter group and an imaging element. The objective lens is used for collecting a plurality of optical signals of different wavebands generated by the to-be-tested sample. The multi-band-pass optical filter set is located between the objective lens and the imaging element and used for receiving and separating the optical signals, collected by the objective lens, of the multiple different wavebands and transmitting the optical signals of the multiple different wavebands to the imaging element at the same time for color imaging, that is, the optical signals of the multiple different wavebands are transmitted to the imaging element for color imaging. By means of the multi-band-pass optical filter set, optical signals of multiple different wave bands can be separated at the same time and transmitted to the imaging element at the same time, crosstalk of the different optical signals during imaging is reduced, the accuracy of the imaging system is improved, the imaging efficiency is greatly improved, the optical imaging system is simple, and the cost is reduced.

Description

Technical Field

[0001] The present invention relates to the fields of molecular biology, optics and computational science and technology, and in particular to an optical imaging system and a biomolecule detection system. Background Art

[0002] Optical imaging technology is widely used in sample detection. For example, in the gene sequencing process, the excitation light emitted by the optical imaging system can excite the biomolecules with optically detectable labels on the surface of the biochip to produce optical signals, and the optical imaging system is used to collect these optical signals to form images. Based on the image analysis, relevant biological information of the biomolecules can be obtained.

[0003] In related technologies, gene sequencing usually adopts a multi-channel method for imaging, and its imaging system is usually a four-channel imaging system or a dual-channel imaging system. However, whether it is a four-channel imaging system or a dual-channel imaging system, when performing gene testing, crosstalk between different optical signals is inevitable, resulting in low shooting efficiency and low accuracy, thereby affecting the test results, and multiple sleeve lenses are required to be set up for separate imaging, which increases the cost of the system. Summary of the invention

[0004] In view of this, the purpose of the present application is to provide an optical imaging system and a biomolecule detection system that can reduce crosstalk, improve shooting efficiency and accuracy, and reduce costs.

[0005] To achieve the above purpose, this application has the following technical solutions:

[0006] The present application provides an optical imaging system, comprising:

[0007] A light source device, used for emitting excitation light to excite the sample to be tested to generate optical signals of multiple different wavelength bands;

[0008] An imaging device, comprising an objective lens, a multi-bandpass filter set and an imaging element;

[0009] The objective lens is used to collect the optical signals of the multiple different wavebands;

[0010] The multi-bandpass filter group is located between the objective lens and the imaging element. The multi-bandpass filter group is used to receive and separate the optical signals of the multiple different bands collected by the objective lens and simultaneously transmit the optical signals of the multiple different bands to the imaging element for color imaging.

[0011] In some embodiments, the light source device is used to emit excitation light to excite the sample to be tested to generate N1 optical signals of different bands, the multi-bandpass filter group includes only one multi-bandpass filter, and the multi-bandpass filter is used to receive and simultaneously separate the N1 optical signals of different bands collected by the objective lens and simultaneously transmit the N1 optical signals of different bands to the imaging element for color imaging; wherein N1 is a natural number equal to or greater than 2.

[0012] In some embodiments, the light source device is used to emit excitation light to excite the sample to be tested to generate optical signals of N different bands, and the multi-bandpass filter group includes M multi-bandpass filters, where 2≤M≤N2-1, and the M multi-bandpass filters are used to receive and simultaneously separate the N2 optical signals of different bands collected by the objective lens and simultaneously transmit the N2 optical signals of different bands to the imaging element for color imaging; wherein M is a natural number greater than or equal to 2, and N2 is a natural number greater than 2.

[0013] In some embodiments, N2 is 4, M is 2, the optical signals of the four different wavebands include a first waveband optical signal, a second waveband optical signal, a third waveband optical signal, and a fourth waveband optical signal, and the two multi-bandpass filters include a first multi-bandpass filter and a second multi-bandpass filter;

[0014] The first multi-bandpass filter is used for simultaneously separating the first-band optical signal and the second-band optical signal, and the second multi-bandpass filter is used for simultaneously separating the third-band optical signal and the fourth-band optical signal.

[0015] In some embodiments, a focusing lens is disposed between the multi-bandpass filter group and the imaging element, and the focusing lens is used to receive the optical signals of the multiple different bands passing through the multi-bandpass filter group and converge the optical signals of the multiple different bands to the imaging element.

[0016] In some embodiments, the light source device includes a multi-wavelength laser generator, which is used to emit multiple single-wavelength excitation lights to excite the sample to be tested to generate optical signals of multiple different wavelength bands.

[0017] In some embodiments, a first dichroic mirror is arranged between the multi-wavelength laser generator and the objective lens, and the first dichroic mirror is located on the optical axis of the objective lens. The first dichroic mirror is used to couple the excitation light into the objective lens so that the excitation light is irradiated onto the sample to be tested through the objective lens, and is used to transmit the optical signals of the multiple different wavelength bands collected by the objective lens.

[0018] In some embodiments, a collimator is provided in the illumination light path of the excitation light, the collimator is located between the objective lens and the multi-wavelength laser generator, and the collimator is used to collimate the excitation light.

[0019] In some embodiments, a light source filter is disposed on the illumination light path of the excitation light, and the light source filter is located between the first dichroic mirror and the collimating mirror.

[0020] In some embodiments, a second dichroic mirror is arranged between the first dichroic mirror and the multi-bandpass filter group, and the second dichroic mirror is located on the optical axis of the objective lens. The second dichroic mirror is used to receive the optical signals of the multiple different bands passing through the first dichroic mirror and reflect the optical signals of the multiple different bands to the multi-bandpass filter group.

[0021] In some embodiments, the optical imaging system also includes an autofocus module, which is used to emit a focusing beam so that the focusing beam is sequentially irradiated onto the sample to be tested after passing through the second dichroic mirror, the first dichroic mirror and the objective lens. The autofocus module is also used to receive the focusing beam reflected from the sample to be tested.

[0022] In some embodiments, the optical imaging system further comprises:

[0023] An image acquisition and recognition module, wherein the image acquisition and recognition module is used to:

[0024] acquiring a color image from the imaging element;

[0025] The colors in the color image are identified to obtain the detection result of the sample to be tested.

[0026] In some embodiments, the image acquisition and recognition module recognizes the color in the color image to obtain the detection result of the sample to be tested, including:

[0027] The image acquisition and recognition module identifies each color in the color image, determines the color coordinates corresponding to each color, determines the band of the optical signal corresponding to each color according to the color coordinates corresponding to each color, and obtains the detection result of the sample to be tested according to the band of the optical signal corresponding to each color.

[0028] In some embodiments, the color coordinates are one of the International Commission on Illumination (CIE) chromaticity coordinates, the three primary colors RGB color space coordinates, the hue-saturation-brightness HIS color space coordinates, the brightness-color difference YUV color space coordinates, the cyan-magenta-yellow CMY color space coordinates, the brightness-color component YIQ model coordinates and the brightness-chroma YCrCb model coordinates.

[0029] The present application provides a biomolecule detection system, characterized by comprising any of the optical imaging systems described above.

[0030] The present application provides an optical imaging system, comprising: a light source device and an imaging device, wherein the light source device is used to emit excitation light to excite a sample to be tested to generate optical signals of multiple different wavelengths. The imaging device comprises an objective lens, a multi-bandpass filter group and an imaging element. The objective lens is used to collect optical signals of multiple different wavelengths generated by the sample to be tested. The multi-bandpass filter group is located between the objective lens and the imaging element, and the multi-bandpass filter group is used to receive and separate optical signals of multiple different wavelengths collected by the objective lens and transmit the optical signals of multiple different wavelengths to the imaging element at the same time for color imaging, that is, the multi-bandpass filter group can be used to achieve simultaneous separation of optical signals of multiple different wavelengths and transmit them to the imaging element at the same time, thereby reducing the crosstalk of different optical signals during imaging and improving the accuracy of the imaging system. In this way, the optical bands can be distinguished directly in the multi-bandpass filter group, and only one imaging element is required to simultaneously image the sample to be tested, which greatly increases the imaging efficiency, and the optical imaging system is simple, reducing the cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0032] Figure 1 A schematic diagram of the structure of an optical imaging system provided in an embodiment of the present application is shown;

[0033] Figure 2 A schematic diagram of the structure of another optical imaging system provided in an embodiment of the present application is shown;

[0034] Figure 3 A schematic diagram of filtering of a multi-bandpass filter set provided in an embodiment of the present application is shown;

[0035] Figure 4 Another filtering schematic diagram of a multi-bandpass filter set provided in an embodiment of the present application is shown;

[0036] Figure 5 A schematic diagram of filtering of another multi-bandpass filter set provided in an embodiment of the present application is shown;

[0037] Figure 6 A schematic diagram of filtering of another multi-bandpass filter set provided in an embodiment of the present application is shown;

[0038] Figure 7 A schematic diagram of filtering of another multi-bandpass filter set provided in an embodiment of the present application is shown. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0040] This application is described in detail with reference to schematic diagrams. When describing the embodiments of this application in detail, for the sake of convenience, the cross-sectional diagrams showing the device structure will not be partially enlarged according to the general scale, and the schematic diagrams are only examples, which should not limit the scope of protection of this application. In addition, in actual production, the three-dimensional dimensions of length, width and depth should be included.

[0041] Optical imaging technology has a wide range of applications in sample detection. For example, optical imaging systems can be used in gene sequencing, which can analyze the base sequence of specific gene (DNA) fragments, that is, the arrangement of adenine (A), thymine (T), cytosine (C) and guanine (G). The function of the optical imaging system in the current gene sequencer is to use lasers to excite the biomolecules with optically detectable labels on the surface of the biochip to generate optical signals, and collect these optical signals to form images. Based on the image analysis, relevant biological information of the biomolecules can be obtained.

[0042] In the related art, gene sequencing is usually imaged in a multi-channel manner, and its imaging system is usually a four-channel imaging system or a dual-channel imaging system. For example, a four-channel imaging system is implemented using space division multiplexing technology, that is, biological molecules are excited simultaneously to generate four optical signals, and then four cameras are used to image the four optical signals separately, that is, one camera is used to image one optical signal, and four images of all optical signals are obtained. A dual-channel imaging system is implemented using time division multiplexing technology and space division multiplexing technology, that is, biological molecules are excited twice to generate optical signals, and each time only two optical signals are excited to generate biological molecules, and two cameras are used to image the two optical signals separately, so that after two times of excitation of biological molecules, four images of all optical signals are obtained.

[0043] However, whether it is a four-channel imaging system or a two-channel imaging system, when performing genetic testing, crosstalk will occur between different optical signals emitted by biological molecules, resulting in low shooting efficiency and low accuracy. And because each channel needs to be equipped with a tube lens, this inevitably increases the risk of processing errors, resulting in a slight fluctuation in the focal length of the tube lens, which makes the magnification of different imaging channels slightly different, and is prone to errors during algorithm alignment. In addition, setting up multiple tube lenses to image each fluorescent signal separately increases the cost of the system.

[0044] Based on this, the present application provides an optical imaging system, including: a light source device and an imaging device, the light source device is used to emit excitation light to excite the sample to be tested to generate multiple optical signals of different bands. The imaging device includes an objective lens, a multi-bandpass filter group and an imaging element. The objective lens is used to collect multiple optical signals of different bands generated by the sample to be tested. The multi-bandpass filter group is located between the objective lens and the imaging element, and the multi-bandpass filter group is used to receive and separate the optical signals of multiple different bands collected by the objective lens and transmit the optical signals of multiple different bands to the imaging element at the same time for color imaging, that is, the multi-bandpass filter group can be used to achieve simultaneous separation of optical signals of multiple different bands and transmit them to the imaging element at the same time, reduce the crosstalk of different optical signals during imaging, and improve the accuracy of the imaging system. In this way, the optical bands can be distinguished directly in the multi-bandpass filter group, and only one imaging element is required to simultaneously image the sample to be tested, the imaging efficiency is greatly increased, and the optical imaging system is simple, reducing the cost.

[0045] In order to better understand the technical solution and technical effects of the present application, specific embodiments will be described in detail below with reference to the accompanying drawings.

[0046] refer to Figure 1 , which is a schematic diagram of the structure of an optical imaging system provided in an embodiment of the present application. The optical imaging system provided in an embodiment of the present application comprises: a light source device 100 and an imaging device.

[0047] The light source device 100 is used to emit excitation light to excite the sample to be tested 10 to generate multiple optical signals of different wavelengths. The sample to be tested 10 can be a nucleic acid sample, and the nucleic acid is, for example, DNA or RNA. The nucleic acid sample is fixed on a sequencing chip, and a fluid channel is provided in the sequencing chip. The inner surface of the fluid channel is connected with a probe (for example, an oligonucleotide) by chemical modification, and the nucleic acid sample is fixed on the sequencing chip after being combined with the probe in a hybridization manner. By adding a variety of free bases (for example, four bases of A / T / C / G) and polymerases, etc., each with different fluorescent markers, the added bases are combined with the bases on the nucleic acid sample according to the principle of complementary pairing, and different fluorescent markers are excited by the excitation light to generate a variety of different colors or a variety of different bands of optical signals.

[0048] Specifically, the light source device 100 includes a first light source, which is, for example, a multi-wavelength laser generator, and the multi-wavelength laser generator is used to emit a plurality of single-wavelength excitation lights to excite the sample 10 to generate optical signals of a plurality of different wavelength bands.

[0049] As an example, the first light source may be a dual-wavelength laser generator, which is used to emit lasers of two specific wavelengths and powers, and the two specific wavelengths of lasers may be red light and green light. Each laser can simultaneously excite two fluorescent markers to produce fluorescence, so that emitting two lasers can excite a total of four fluorescent markers, and the four fluorescent markers correspond to adenine (A), thymine (T), cytosine (C) and guanine (G), respectively. After the four fluorescent markers are excited by the laser, they will generate optical signals of four different bands. For example, the optical signal of the 551 nanometer (nm)-571nm band corresponds to adenine (A), the optical signal of the 595nm-615nm band corresponds to thymine (T), the optical signal of the 662nm-682nm band corresponds to guanine (G), and the optical signal of the 702nm-722nm band corresponds to cytosine (C).

[0050] The imaging device includes an objective lens 210 , a multi-bandpass filter set 220 and an imaging element 230 .

[0051] The objective lens 210 is disposed on the optical path between the sample 10 and the light source device 100, and is used to receive and converge the excitation light beam to the sample 10, and to collect optical signals of multiple different wavelength bands excited by the laser of the sample 10. The focal length of the objective lens 210 can be adjusted according to actual conditions.

[0052] The imaging element 230 is an element that can capture optical signals and perform color imaging, that is, the imaging element 230 can capture optical signals and perform photoelectric conversion into a color image, and output the color image. The number of imaging elements 230 is 1. The imaging element 230 is located on the optical axis of the objective lens 210. For example, the imaging element 230 can be a color camera. The color camera can be, for example, a color CCD camera, a color CMOS (Complementary Metal Oxide Semiconductor) camera, or a color sCMOS (Scientific COMS) camera. The number of color cameras is one. In one embodiment, the scanning mode of the color camera can adopt a frame acquisition mode or a line scanning mode. In another embodiment, the color camera can adopt a static imaging mode or a mobile imaging mode for color imaging.

[0053] The multi-bandpass filter group 220 is located between the objective lens 210 and the imaging element 230, and specifically can be located on the optical path between the objective lens 210 and the imaging element 230. The multi-bandpass filter group 220 is used to receive and separate optical signals of multiple different wavelengths collected by the objective lens 210 and transmit the optical signals of multiple different wavelengths to the imaging element 230 simultaneously for color imaging. The multi-bandpass filter group 220 can cut off the excitation light and simultaneously separate optical signals of at least two different wavelengths.

[0054] That is to say, the multi-bandpass filter group 220 can separate multiple optical signals according to bands, so that the multiple optical signals can be distinguished by bands after passing through the multi-bandpass filter group 220, and then when imaging to the imaging element 230, the imaging element 230 can simultaneously record and effectively distinguish different optical signals.

[0055] It can be seen that the use of the multi-bandpass filter set 220 can achieve simultaneous separation of optical signals of multiple different bands and transmit them to the imaging element 230 at the same time, reduce the crosstalk of different optical signals during imaging, and improve the accuracy of the optical imaging system. In this way, the optical bands can be distinguished directly in the multi-bandpass filter set 220, and only one imaging element 230 is required to simultaneously image the sample 10 to be tested, which greatly increases the imaging efficiency, and the optical imaging system is simple, reducing costs.

[0056] As an example, the multi-bandpass filter set 220 can receive and separate optical signals of four different wavelength bands and transmit the optical signals of four different wavelength bands to the imaging element 230 for color imaging at the same time. In this way, the fluorescence of four-color bases can be recorded in one shot in a single channel, and the four-color bases can be effectively distinguished by the multi-bandpass filter set 220, with high shooting efficiency and accuracy and low system cost.

[0057] In the embodiment of the present application, the number of multi-bandpass filters included in the multi-bandpass filter group 220 may be one or more, which is described in detail below:

[0058] The first possible implementation is that the number of multi-bandpass filters included in the multi-bandpass filter group 220 is 1. When the light source device 100 emits excitation light to excite the sample to be tested 10 to generate N1 optical signals of different bands, the multi-bandpass filter is used to receive and simultaneously separate the optical signals of N1 different bands collected by the objective lens 210 and simultaneously transmit the optical signals of N1 different bands to the imaging element 230 for color imaging, wherein N1 is a natural number equal to or greater than 2. In other words, only one multi-bandpass filter can be used to separate the optical signals of all bands generated by the excitation. If the light source device 100 generates at least 2 bands of optical signals, then one multi-bandpass filter can capture at least 2 bands of optical signals. In this way, only one imaging element 230 is needed to simultaneously image the optical signals of at least 2 bands, which greatly improves the imaging efficiency. In addition, one channel is used for imaging, which reduces channel crosstalk and improves the imaging accuracy.

[0059] As an example, when the light source device 100 emits red excitation light and green excitation light to excite the sample 10 to generate optical signals of four different wavelengths, a multi-bandpass filter is used to cut off the red excitation light and the green excitation light, and receive and simultaneously separate the optical signals of four different wavelengths collected by the objective lens 210. Figure 3 As shown, the multi-bandpass filter separates optical signals of four different bands, including optical signals of a 551nm-571nm band, an optical signal of a 595nm-615nm band, an optical signal of a 662nm-682nm band, and an optical signal of a 702nm-722nm band.

[0060] As another example, when the light source device 100 emits red excitation light and green excitation light to excite the sample 10 to generate optical signals of three different wavelength bands, a multi-bandpass filter is used to cut off the red excitation light and the green excitation light, and receive and simultaneously separate the optical signals of the three different wavelength bands collected by the objective lens 210. Figure 4 As shown, the multi-bandpass filter separates optical signals of three different bands, including optical signals of a 551nm-571nm band, an optical signal of a 595nm-615nm band, and an optical signal of a 702nm-722nm band.

[0061] As another example, when the light source device 100 emits red excitation light and green excitation light to excite the sample 10 to generate optical signals of two different wavelengths, a multi-bandpass filter is used to cut off the red excitation light and the green excitation light, and receive and simultaneously separate the optical signals of the two different wavelengths collected by the objective lens 210. Figure 5 As shown, the multi-bandpass filter separates optical signals of two different bands including optical signals of a 551nm-571nm band and optical signals of a 702nm-722nm band.

[0062] The second possible implementation is that the number of multi-bandpass filters included in the multi-bandpass filter group 220 is multiple. The multi-bandpass filter group 220 includes M multi-bandpass filters. When the light source device 100 emits excitation light to excite the sample to be tested 10 to generate N2 optical signals of different bands, where 2≤M≤N2-1, the M multi-bandpass filters are used to receive and simultaneously separate the optical signals of N2 different bands collected by the objective lens 210 and transmit the optical signals of N2 different bands to the imaging element for color imaging, where M is a natural number greater than or equal to 2, and N2 is a natural number greater than 2. M multi-bandpass filters simultaneously separate N2 optical signals of different bands, so that the optical signals separated by different multi-bandpass filters have different bands, and the combination can achieve the simultaneous separation of N2 optical signals of different bands.

[0063] As an embodiment, the multi-bandpass filter group 220 includes two multi-bandpass filters, and the two multi-bandpass filters include a first multi-bandpass filter and a second multi-bandpass filter. The light source device 100 emits excitation light to excite the sample to be tested 10 to generate optical signals of four different bands, and the four optical signals of four different bands include a first band optical signal, a second band optical signal, a third band optical signal and a fourth band optical signal. The first multi-bandpass filter is used to simultaneously separate the first band optical signal and the second band optical signal, and simultaneously transmit the first band optical signal, the second band optical signal, the third band optical signal and the fourth band optical signal, that is, the first multi-bandpass filter cannot separate the third band optical signal and the fourth band optical signal, and can only separate the first band optical signal and the second band optical signal. The second multi-bandpass filter is used to simultaneously separate the third-band optical signal and the fourth-band optical signal, and simultaneously transmit the first-band optical signal, the second-band optical signal, the third-band optical signal and the fourth-band optical signal, that is, the second multi-bandpass filter cannot separate the first-band optical signal and the second-band optical signal, and can only separate the third-band optical signal and the fourth-band optical signal. In this way, the combination of the first multi-bandpass filter and the second multi-bandpass filter can realize the simultaneous separation of the optical signals of the four bands, and there is only one imaging optical path, and there is only one imaging element 230, which can avoid the complexity of the optical path and reduce channel crosstalk.

[0064] As an example, the first wavelength band optical signal is an optical signal in the wavelength band of 551nm-571nm, the second wavelength band optical signal is an optical signal in the wavelength band of 595nm-615nm, the third wavelength band optical signal is an optical signal in the wavelength band of 662nm-682nm, and the fourth wavelength band optical signal is an optical signal in the wavelength band of 702nm-722nm. Figure 6 As shown, the first multi-bandpass filter separates optical signals of two different bands, including optical signals of a 551nm-571nm band and optical signals of a 595nm-615nm band, and the second multi-bandpass filter separates optical signals of two different bands, including optical signals of a 662nm-682nm band and optical signals of a 702nm-722nm band.

[0065] As another embodiment, the multi-bandpass filter group 220 includes two multi-bandpass filters, and the two multi-bandpass filters include a first multi-bandpass filter and a second multi-bandpass filter. The light source device 100 emits excitation light to excite the sample to be tested 10 to generate three optical signals of different wavelengths, and the three optical signals of different wavelengths include a first wavelength band optical signal, a second wavelength band optical signal, and a third wavelength band optical signal. The first multi-bandpass filter is used to simultaneously separate the first wavelength band optical signal and the second wavelength band optical signal, and simultaneously transmit the first wavelength band optical signal, the second wavelength band optical signal, and the third wavelength band optical signal. The second multi-bandpass filter is used to simultaneously separate the third wavelength band optical signal, and simultaneously transmit the first wavelength band optical signal, the second wavelength band optical signal, and the third wavelength band optical signal.

[0066] As an example, the first wavelength band optical signal is an optical signal in the wavelength band of 551nm-571nm, the second wavelength band optical signal is an optical signal in the wavelength band of 595nm-615nm, and the third wavelength band optical signal is an optical signal in the wavelength band of 702nm-722nm. Figure 7 As shown, the first multi-bandpass filter separates optical signals of two different bands including optical signals of 551nm-571nm band and optical signals of 595nm-615nm band, and the second multi-bandpass filter separates optical signals of one different band including optical signals of 702nm-722nm band.

[0067] In an embodiment of the present application, the optical imaging system further includes a focusing lens 240. Figure 2As shown, the focusing lens 240 is disposed between the multi-bandpass filter set 220 and the imaging element 230, and specifically, the focusing lens 240 is disposed on the optical path between the objective lens 210 and the imaging element 230. The focusing lens 240 is used to receive optical signals of multiple different wavelength bands passing through the multi-bandpass filter set 220 and converge the optical signals of multiple different wavelength bands to the imaging element 240. The focusing lens 240 can be a single lens or multiple lenses. For example, the focusing lens 240 can be a tube lens.

[0068] In the embodiment of the present application, the optical imaging system further includes a dichroic mirror group, which includes a first dichroic mirror 310 and a second dichroic mirror 320. A dichroic mirror, also known as a two-color mirror, is commonly used in laser technology. Its characteristic is that it almost completely transmits light of a certain wavelength and almost completely reflects light of other wavelengths. Therefore, by applying this characteristic of the dichroic mirror, reflection and transmission of the light path can be achieved.

[0069] refer to Figure 2 As shown, the first dichroic mirror 310 can be arranged between the light source device 100 and the objective lens 210. When the light source device 100 is a multi-wavelength laser generator, the first dichroic mirror 310 is arranged between the multi-wavelength laser generator and the objective lens 210. In addition, the first dichroic mirror 310 is arranged on the optical axis of the objective lens 210. The first dichroic mirror 310 and the optical axis are arranged at an angle of 45°, so that the first dichroic mirror 310 couples the excitation light into the objective lens 210 at a right angle, that is, the first dichroic mirror 310 can fully reflect the excitation light, so that the excitation light is irradiated on the sample 10 to be tested through the objective lens 210. When the sample 10 to be tested is excited by the excitation light to generate optical signals of multiple wavelength bands, the first dichroic mirror 310 can transmit the optical signals of multiple different wavelength bands collected by the objective lens 210.

[0070] The second dichroic mirror 320 is disposed between the first dichroic mirror 310 and the multi-bandpass filter set 220. Figure 2 As shown, the second dichroic mirror 320 is disposed on the optical axis of the objective lens 210, and the second dichroic mirror 320 is disposed at a 45° angle to the optical axis. The second dichroic mirror 320 can receive optical signals of multiple different wavelength bands passing through the first dichroic mirror 310 and reflect the optical signals of multiple different wavelength bands at right angles to the multi-bandpass filter set 220.

[0071] In the embodiment of the present application, the optical imaging system further includes an autofocus module 400, referring to Figure 2 As shown, the autofocus module 400 is used to emit a focusing beam so that the focusing beam is sequentially irradiated onto the sample to be tested 10 after passing through the second dichroic mirror 320, the first dichroic mirror 310 and the objective lens 210. The autofocus module 400 is also used to receive the focusing beam reflected from the sample to be tested 10 to detect whether the sample to be tested 10 is located on the focal plane of the objective lens.

[0072] Specifically, the autofocus module 400 includes a second light source, a sensor and an information processing module. The second light source can be, for example, an infrared light source, which is used to emit a focus beam. The focus beam has a specific shape. The emitted focus beam is transmitted to the objective lens 210 through the second dichroic mirror 320 and the first dichroic mirror 310, and the objective lens 210 focuses the focus beam on the sample to be tested 10. The sensor is used to receive the focus beam reflected from the sample to be tested 10. The information processing module is connected to the sensor, and the information processing module is used to obtain beam information from the sensor. The autofocus module 400 also includes an information output module, which is used to output changes in beam information so that the platform carrying the sample to be tested 10 drives the sample to be tested 10 to move to the object plane of the imaging device. In this embodiment, high-precision focusing can be achieved using the autofocus module 400.

[0073] In one embodiment, the optical imaging system may further include a focus filter 410, Figure 2 As shown, the focus filter 410 is disposed between the autofocus module 400 and the second dichroic mirror 320. The focus filter 410 is a device that selectively transmits light of different wavelengths, and is usually a flat glass or plastic device in the optical path, which is dyed or has an interference coating. Furthermore, the focus filter 410 is divided into a passband filter and a cutoff filter according to spectral characteristics, and is divided into an absorption filter and an interference filter according to spectral analysis. In this embodiment, the focus filter 410 is a passband filter for filtering non-effective light in the focus beam. In other embodiments, the passband filter can be replaced by a plurality of negative notch filters.

[0074] When the optical imaging system further includes an autofocus module 400, the second dichroic mirror 320 is used to transmit the focus beam emitted by the autofocus module 400, so that the focus beam reaches the objective lens 210 through the first dichroic mirror 310, and transmits the focus beam reflected from the sample to be tested 10 after being focused by the objective lens 210. In this embodiment, the first dichroic mirror 310 and the second dichroic mirror 320 can be used to achieve the propagation of the mixed wavelength laser, the focus beam, and optical signals of multiple wavelength bands on the same path, that is, the propagation direction of the optical signals of multiple wavelength bands is opposite to the propagation direction of the mixed wavelength laser and the focus beam, but the paths overlap, and the combination design of the first dichroic mirror 310 and the second dichroic mirror 320 can effectively filter out non-effective light. It is understandable that the present embodiment only illustrates one arrangement of the first dichroic mirror 310 and the second dichroic mirror 320. In other embodiments, the first dichroic mirror 310 and the second dichroic mirror 320 may be arranged in a variety of ways, as long as the requirements of achieving the propagation of mixed wavelength lasers, focused light beams, and optical signals of multiple bands on the same path and filtering out non-effective light are met.

[0075] In an embodiment of the present application, the optical imaging system further includes a collimator 110. Figure 2 As shown, the collimator 110 is disposed between the light source device 100 and the objective lens 210. When the light source device 100 is a multi-wavelength laser generator, the collimator 110 is disposed between the multi-wavelength laser generator and the objective lens 210. If the optical imaging system further includes a first dichroic mirror 310, the collimator 110 is disposed between the light source device 100 and the first dichroic mirror 310. The collimator 110 is disposed on the illumination optical path of the excitation light and is used to collimate the excitation light. In this embodiment, the collimator 110 can be used to collimate and shape the mixed wavelength laser to obtain a mixed wavelength laser with a specific spot shape and size.

[0076] In an embodiment of the present application, the optical imaging system further includes a light source filter 120. Figure 2 As shown, the light source filter 120 is disposed between the collimating mirror 110 and the first dichroic mirror 310 . The light source filter 120 is disposed on the illumination light path of the excitation light to filter out the ineffective light in the excitation light.

[0077] In an embodiment of the present application, the optical imaging system also includes an image acquisition and recognition module. The imaging element 230 collects optical signals of multiple bands and converts them into a color image, which can be transmitted to the image acquisition and recognition module for signal recognition, such as being transmitted to a computer through an appropriate interface to achieve signal recognition. Currently, multiple monochrome cameras are generally used to collect optical signals of each band, and bases are identified by determining the intensity of different optical signals in the monochrome image. In this embodiment, an imaging element 230 is used to collect and image optical signals of multiple bands in the same time period, and color images of multiple colors can be obtained. Through color recognition, the detection of the sample 10 to be tested can be realized at the same time (one photo) to obtain the detection result, for example, the recognition of four bases is realized, and the base recognition result is obtained, which shortens the process time and has high detection efficiency.

[0078] Specifically, the color coordinates of each color can be obtained in advance, and the color coordinates can be one of the International Commission on Luminous Illumination (CIE) chromaticity coordinates, three primary colors (RGB) color space coordinates, hue-color saturation-brightness (HIS) color space coordinates, brightness-color difference (YUV) color space coordinates, cyan-magenta-yellow (CMY) color space coordinates, brightness-color component (YIQ) model coordinates, and brightness-chromaticity (YCrCb) model coordinates. The corresponding relationship between the color coordinates of each color and the band of the optical signal of each color can also be obtained in advance. In this way, the image acquisition and recognition module can be used to identify each color in the color image later, determine the color coordinates corresponding to each color, determine the band of the optical signal corresponding to each color according to the color coordinates corresponding to each color and the above-mentioned corresponding relationship, and obtain the detection result of the sample 10 to be tested according to the band of the optical signal corresponding to each color, that is, obtain the base recognition result according to the band of the optical signal corresponding to each color.

[0079] The following is a specific introduction using CIE chromaticity coordinates as an example:

[0080] The image acquisition and recognition module recognizes each color in the color image and determines the color coordinates corresponding to each color according to the CIE color gamut diagram. Since the CIE color gamut diagram includes a horizontal coordinate (X) and a vertical coordinate (Y), the color coordinates also include X and Y.

[0081] The correspondence between the color coordinates of each color and the wavelength band of the optical signal is as follows:

[0082] Optical signal in the 551nm-571nm band: 0.3473≤X≤0.4790, 0.5210≤Y≤0.6501.

[0083] Optical signal in the 595nm-615nm band: 0.6116≤X≤0.6731, 0.3269≤Y≤0.3884.

[0084] Optical signal in the 662nm-682nm band: 0.7168≤X≤0.7198, 0.2802≤Y≤0.2832.

[0085] Optical signal in the 702nm-722nm band: 0.7199≤X≤0.7204, 0.2796≤Y≤0.2801.

[0086] The wavelength band of the optical signal corresponding to the color coordinates of each color is determined according to the above correspondence, and then the base recognition result is determined by the wavelength band of the optical signal.

[0087] It can be seen that in the optical imaging system provided by the embodiment of the present application, the mixed wavelength laser generated by the light source device 100 is reflected at a right angle to the objective lens 210 through the first dichroic mirror 310, and the objective lens 210 focuses the mixed wavelength laser on the sample to be tested 10, and excites the sample to be tested 10 to emit optical signals of multiple bands. The autofocus module 400 emits a focus beam, which is transmitted to the objective lens 210 through the second dichroic mirror 320 and the first dichroic mirror 310, and finally focused on the sample to be tested 10. The focus beam reflected from the sample to be tested 10 returns to the autofocus module 400 along the original optical path. The optical signals of multiple bands are focused and amplified by the objective lens 210, transmitted through the first dichroic mirror 310 and reflected by the second dichroic mirror 320 to the multi-bandpass filter group 220, and the optical signals of multiple bands are separated by the multi-bandpass filter 220, and converged and imaged by the focusing lens 240 to reach the imaging element 230. In this process, the multi-bandpass filter group 220 cuts off the mixed wavelength laser and the focus beam, and separates the optical signals of multiple bands, so that only the optical signals of multiple bands reach the imaging element 230. The imaging element 230 collects the optical signals of multiple bands and converts them into color images, which can be transmitted to the image acquisition and recognition module for signal recognition.

[0088] The optical path of the optical imaging system provided by the embodiment of the present application has only one imaging optical path, which reduces the cost and simplifies the optical path. Compared with a dual-channel or four-channel optical imaging system, there is no need to debug axial chromatic aberration and rotational offset, which greatly saves production debugging man-hours and reduces the difficulty of debugging. In addition, the volume of the optical imaging system will also be reduced. In addition, the optical imaging system provided by the embodiment of the present application includes only one focusing lens, which is a single channel. Compared with a dual-channel binocular lens or a four-channel quadruple lens, it avoids the problem of inaccurate imaging caused by differences between the tube lenses.

[0089] Compared with a dual-channel or quad-channel optical imaging system, the optical imaging system provided in the embodiment of the present application only needs to take a photo once for the same field of view (FOV) (a four-channel optical imaging system needs to take photos four times for the same FOV), which greatly improves the photo-taking speed and the imaging efficiency.

[0090] In addition, since the optical imaging system provided in the embodiment of the present application can collect optical signals of multiple different bands with the same field of view (FOV) by taking a single photo, there is no channel crosstalk, and the spectral interference is a fixed value because there is only one imaging optical path, and the algorithm does not need to perform crosstalk calculation. In addition, since the optical imaging system provided in the embodiment of the present application identifies bases by color, the lower limit requirement for the signal intensity of the bases will be reduced, and the recognition ability will be greatly improved.

[0091] The present application also provides a biomolecule detection system, including the optical imaging system described in the above embodiment. The above biomolecule detection system uses a mixed wavelength laser to excite the sample to be tested, and the sample to be tested emits optical signals of multiple bands, and the optical signals of multiple bands are collected for imaging, and the imaging optical signals are collected to output color images, thereby efficiently completing the determination of gene sequences. The structure of the optical imaging system for generating color images and the propagation path of the optical path have been given and will not be repeated here.

[0092] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referenced to each other, and each embodiment focuses on the differences from other embodiments.

[0093] The descriptions of the processes or structures corresponding to the above-mentioned figures have different emphases. For parts that are not described in detail in a certain process or structure, please refer to the relevant descriptions of other processes or structures.

[0094] The above is only a preferred implementation of the present application. Although the present application has been disclosed as a preferred embodiment, it is not intended to limit the present application. Any technician familiar with the art can use the above disclosed methods and technical contents to make many possible changes and modifications to the technical solution of the present application without departing from the scope of the technical solution of the present application, or modify it into an equivalent embodiment of equivalent changes. Therefore, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present application without departing from the content of the technical solution of the present application still falls within the scope of protection of the technical solution of the present application.

[0095] Based on the implementations provided in the above aspects, this application can also be further combined to provide more implementations.

Claims

1. An optical imaging system, characterized in that: include: A light source device, used for emitting excitation light to excite the sample to be tested to generate optical signals of multiple different wavelength bands; An imaging device, comprising an objective lens, a multi-bandpass filter set and an imaging element; The objective lens is used to collect the optical signals of the multiple different wavebands; The multi-bandpass filter group is located between the objective lens and the imaging element. The multi-bandpass filter group is used to receive and separate the optical signals of the multiple different bands collected by the objective lens and simultaneously transmit the optical signals of the multiple different bands to the imaging element for color imaging.

2. The optical imaging system according to claim 1, characterized in that: The light source device is used to emit excitation light to excite the sample to be tested to generate N1 optical signals of different wavelengths. The multi-bandpass filter group includes only one multi-bandpass filter. The multi-bandpass filter is used to receive and simultaneously separate the optical signals of the N1 different wavelengths collected by the objective lens and simultaneously transmit the optical signals of the N1 different wavelengths to the imaging element for color imaging. Wherein, N1 is a natural number equal to or greater than 2.

3. The optical imaging system according to claim 1, characterized in that: The light source device is used to emit excitation light to excite the sample to be tested to generate optical signals of N2 different bands, the multi-bandpass filter group includes M multi-bandpass filters, wherein 2≤M≤N2-1, and the M multi-bandpass filters are used to receive and simultaneously separate the optical signals of N2 different bands collected by the objective lens and simultaneously transmit the optical signals of N2 different bands to the imaging element for color imaging; Wherein, M is a natural number greater than or equal to 2, and N2 is a natural number greater than 2.

4. The optical imaging system according to claim 3, characterized in that: The N2 is 4, the M is 2, the optical signals of the four different wavebands include a first waveband optical signal, a second waveband optical signal, a third waveband optical signal and a fourth waveband optical signal, and the two multi-bandpass optical filters include a first multi-bandpass optical filter and a second multi-bandpass optical filter; The first multi-bandpass filter is used for simultaneously separating the first-band optical signal and the second-band optical signal, and the second multi-bandpass filter is used for simultaneously separating the third-band optical signal and the fourth-band optical signal.

5. The optical imaging system according to any one of claims 1 to 4, characterized in that: A focusing lens is arranged between the multi-bandpass filter group and the imaging element, and the focusing lens is used to receive the optical signals of the multiple different wavelength bands passing through the multi-bandpass filter group and converge the optical signals of the multiple different wavelength bands to the imaging element.

6. The optical imaging system according to any one of claims 1 to 5, characterized in that: The light source device comprises a multi-wavelength laser generator, and the multi-wavelength laser generator is used to emit a plurality of single-wavelength excitation lights to excite the sample to be tested to generate optical signals of a plurality of different wavelength bands; Optionally, a first dichroic mirror is arranged between the multi-wavelength laser generator and the objective lens, the first dichroic mirror is located on the optical axis of the objective lens, the first dichroic mirror is used to couple the excitation light into the objective lens so that the excitation light is irradiated onto the sample to be measured through the objective lens, and is used to transmit the optical signals of the multiple different wavelength bands collected by the objective lens; Optionally, a collimator is provided on the illumination optical path of the excitation light, the collimator is located between the objective lens and the multi-wavelength laser generator, and the collimator is used to collimate the excitation light; Optionally, a light source filter is provided on the illumination light path of the excitation light, and the light source filter is located between the first dichroic mirror and the collimating mirror; Optionally, a second dichroic mirror is arranged between the first dichroic mirror and the multi-bandpass filter group, the second dichroic mirror is located on the optical axis of the objective lens, and the second dichroic mirror is used to receive the optical signals of the multiple different wavebands passing through the first dichroic mirror and reflect the optical signals of the multiple different wavebands to the multi-bandpass filter group; Optionally, the optical imaging system also includes an autofocus module, which is used to emit a focusing beam so that the focusing beam is sequentially irradiated onto the sample to be tested after passing through the second dichroic mirror, the first dichroic mirror and the objective lens. The autofocus module is also used to receive the focusing beam reflected from the sample to be tested.

7. The optical imaging system according to any one of claims 1 to 6, characterized in that: The optical imaging system further comprises: An image acquisition and recognition module, wherein the image acquisition and recognition module is used to: acquiring a color image from the imaging element; The colors in the color image are identified to obtain the detection result of the sample to be tested.

8. The optical imaging system according to claim 7, characterized in that: The image acquisition and recognition module recognizes the colors in the color image to obtain the detection result of the sample to be tested, including: The image acquisition and recognition module identifies each color in the color image, determines the color coordinates corresponding to each color, determines the band of the optical signal corresponding to each color according to the color coordinates corresponding to each color, and obtains the detection result of the sample to be tested according to the band of the optical signal corresponding to each color.

9. The optical imaging system according to claim 8, characterized in that: The color coordinates are one of the International Commission on Illumination (CIE) chromaticity coordinates, the three primary colors RGB color space coordinates, the hue-saturation-brightness HIS color space coordinates, the brightness-color difference YUV color space coordinates, the cyan-magenta-yellow CMY color space coordinates, the brightness-color component YIQ model coordinates and the brightness-chroma YCrCb model coordinates.

10. A biomolecule detection system, characterized in that: An optical imaging system comprising any one of claims 1-9.

Images