Nanoflow type light receiving device
By setting up an adjustment mechanism in the nanoflow light-receiving device to automatically adjust the eccentricity, tilt and focal surface of the light-receiving objective lens, the problem of weakening of optical signals in the nanoflow type is solved, and automatic precise adjustment and stability of optical signals are achieved.
Patent Information
- Application Number
- CN202411871808.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-18
- Publication Date
- 2025-03-25
AI Technical Summary
In nanoflow optical detection, since the deviation amount is very small and the detection sample is in a flowing state, the static tolerance control cannot satisfy the maintenance of the optical signal, resulting in weakening of the optical signal.
By setting up an adjustment mechanism to automatically and accurately adjust the eccentricity, inclination and focal surface of the light receiving objective lens, the automatic adjustment of the signal light position and the light receiving surface are achieved to ensure the automatic maintenance of the optical signal.
Automatic and accurate adjustment of optical signals is realized to ensure the intensity and stability of the optical signal received by the detector, and solve the optical signal attenuation problems caused by particle position and detection focal surface fluctuations in nanoflow.
Smart Images
Figure CN119688558A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of optical instruments, and in particular to a nano-flow light collecting device. Background Art
[0002] In the signal detection optical path, the actual detection effect of the optical signal depends on the deviation between the actual position of the device in the optical path and the ideal position, including deviations in eccentricity, tilt and focal plane. These deviations will change the path of light propagation to the detector, thereby weakening the optical signal. In optical design, tolerance analysis and design are usually used to avoid this problem. However, in nanoflow optical detection, since the deviation is very small and the detection sample is in a flowing state, static tolerance control cannot meet the requirements for maintaining the optical signal. Summary of the invention
[0003] In view of this, the embodiments of the present specification provide a nanoflow light collecting device, which can realize automatic and precise adjustment of the eccentricity, tilt and focal plane of the light collecting objective lens by setting an adjustment mechanism, so as to realize automatic adjustment of the signal light position and the light collecting focal plane in the nanoflow, and automatically maintain the optical signal, thereby ensuring that the intensity and stability of the optical signal received by the detector are automatically and precisely adjusted.
[0004] The embodiments of this specification provide the following technical solutions: a nano-flow light collecting device, which uses the form of front flow focusing to transfer sample liquid, and the light collecting device includes:
[0005] A sheath flow portion, wherein the sheath flow portion is used for nano sample particles in the sample liquid to pass through under the focusing effect of the sheath liquid;
[0006] A light source, wherein the light source emits an illumination light beam that converges on the sample liquid in the sheath flow portion, so that the nano sample particles are excited to emit scattered light signals and fluorescence signals;
[0007] A light-collecting objective lens, wherein the object focus of the light-collecting objective lens is aligned with the light source of the scattered light signal and the fluorescent signal;
[0008] A detector, the detector is used to receive the optical signal transmitted by the light-collecting objective lens and complete the conversion and detection of the optical signal;
[0009] An adjusting mechanism is used to automatically adjust the eccentricity and / or tilt and / or focal plane of the light-collecting lens of the light-collecting objective lens according to the optical signal received by the detector.
[0010] Preferably, the adjustment mechanism includes a first translation stage, a second translation stage and a rotating stage, the first translation stage and the second translation stage are orthogonally distributed, the first translation stage is used to correct the eccentricity deviation of the light-collecting objective lens, the second translation stage is used to correct the defocus deviation of the light-collecting objective lens, and the rotating stage is used to correct the tilt deviation of the light-collecting objective lens.
[0011] Preferably, the second translation stage is in the same direction as the axis of the light-collecting objective lens.
[0012] Preferably, the stroke of the first translation stage covers the fluctuation variation of the optical axis of the optical signal in the X direction, and the stroke range is 1 mm to 20 mm;
[0013] The stroke of the second translation stage covers the fluctuation variation of the optical axis of the optical signal in the Y direction, and the stroke range is 1 mm to 20 mm;
[0014] The rotation angle of the rotating stage covers the tilt deviation of the optical axis of the optical signal, and the rotation angle is 1° to 10°.
[0015] Preferably, the adjustment step length of the first translation stage is 0.1 μm to 10 μm;
[0016] The adjustment step length of the second translation stage is 0.1 μm to 10 μm;
[0017] The adjustment step length of the rotating table is 0.01° to 0.05°.
[0018] Preferably, the numerical aperture of the light-collecting objective lens is between 1 and 1.2.
[0019] Preferably, the illumination light beam is a collimated light beam output by optical fiber or spatial light, and the aperture of the collimated light beam is any value between 0.1 mm and 2 mm.
[0020] Preferably, the energy density of the spot where the illumination light beam converges onto the axial flow is 10 4 ~10 6 W / mm 2 Magnitude.
[0021] Preferably, the illumination light beam is a monochromatic laser;
[0022] Alternatively, the illumination light beam is a plurality of monochromatic laser beams with different wavelengths.
[0023] Preferably, the detector may be one of APD, PMT, and MPPC photoelectric sensors, and the diameter of the detector target surface is 1 mm to 10 mm.
[0024] Compared with the prior art, the at least one technical solution adopted in the embodiments of this specification can achieve the following beneficial effects:
[0025] The sample is transmitted in the form of front flow focusing. The nano-sample particles in the sample liquid pass through the center of the sheath flow part in a queue under the focusing effect of the sheath liquid. The illumination light beam emitted by the light source converges on the sample liquid in the sheath flow part, and the light-collecting objective lens collects the light. The signal light position and the light-collecting focal plane are automatically and finely adjusted through the adjustment mechanism. The optical signal is automatically maintained, thereby ensuring that the intensity and stability of the optical signal received by the detector are automatically and accurately adjusted. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
[0027] Figure 1 It is a structural schematic diagram of the nano-flow light collecting device provided by the present application;
[0028] Figure 2 It is a schematic diagram of the optical path of the nano-flow light collecting device provided in this application.
[0029] In the figure, 1, light-collecting objective lens; 2, detector; 3, rotating stage; 4, first translation stage; 5, second translation stage; 6, sheath fluid; 7, sample fluid; 8, illumination beam; 9, sheath flow unit. DETAILED DESCRIPTION
[0030] The embodiments of the present application are described in detail below with reference to the accompanying drawings.
[0031] The following describes the implementation methods of the present application through specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The present application can also be implemented or applied through other different specific implementation methods, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that, in the absence of conflict, the following embodiments and the features in the embodiments can be combined with each other. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present application.
[0032] It should be noted that various aspects of the embodiments within the scope of the appended claims are described below. It should be apparent that the aspects described herein can be embodied in a wide variety of forms, and any specific structure and / or function described herein is merely illustrative. Based on the present application, it should be understood by those skilled in the art that an aspect described herein can be implemented independently of any other aspect, and two or more of these aspects can be combined in various ways. For example, any number and aspect described herein can be used to implement the device and / or practice the method. In addition, other structures and / or functionalities other than one or more of the aspects described herein can be used to implement this device and / or practice this method.
[0033] It should also be noted that the illustrations provided in the following embodiments are only schematic illustrations of the basic concept of the present application. The drawings only show components related to the present application rather than being drawn according to the number, shape and size of components in actual implementation. In actual implementation, the type, quantity and proportion of each component may be changed arbitrarily, and the component layout may also be more complicated.
[0034] Additionally, in the following description, specific details are provided to facilitate a thorough understanding of the examples. However, it will be understood by those skilled in the art that the aspects described may be practiced without these specific details.
[0035] In the signal detection optical path, the actual detection effect of the optical signal depends on the deviation between the actual position of the device in the optical path and the ideal position, including deviations in eccentricity, tilt and focal plane. These deviations will change the path of light propagation to the detector, thereby weakening the optical signal. In optical design, tolerance analysis and design are usually used to avoid this problem. However, in nanoflow optical detection, since the deviation is very small and the detection sample is in a flowing state, static tolerance control cannot meet the requirements for maintaining the optical signal.
[0036] In order to improve the light collection efficiency in nanoflow devices, a lens with a large numerical aperture (NA) is required to collect light, usually with a numerical aperture of more than 1.0. In the case of a large numerical aperture, the lens working distance is required to be very small, reaching the millimeter level, and the eccentricity, tilt and focal plane of the lens are very sensitive.
[0037] After extensive and in-depth experiments, the inventor designed a nano-flow light collecting device.
[0038] The technical problems solved by the present invention are:
[0039] Solve the problem of optical signal attenuation caused by particle position fluctuation in nanofluidics;
[0040] Solve the problem of optical signal attenuation caused by focal plane fluctuation of particle detection in nanofluidics.
[0041] The technical solutions provided by various embodiments of the present application are described below in conjunction with the accompanying drawings.
[0042] like Figure 1-Figure 2 As shown, a nano-flow light collecting device adopts the form of front flow focusing to transmit the sample liquid 7, and the light collecting device includes:
[0043] A sheath flow section 9, wherein the sheath flow section 9 is used for the nano-sample particles in the sample liquid 7 to pass through under the focusing effect of the sheath liquid 6. The sheath flow section 9 includes a transparent flow chamber. The nano-sample particles in the sample liquid 7 form a flow focus through the sheath liquid 6 in the flow chamber. The nano-sample particles in the sample liquid 7 pass through the center of the flow chamber in a queue in sequence under the focusing effect of the sheath liquid 6. The sheath liquid 6 can be deionized water or a saline solution. The flow rate of the sheath liquid 6 can be 1 μL / min to 5 mL / min, and the sample flow rate can be 1 nL / min to 50 μL / min.
[0044] A light source, wherein the light source emits an illumination light beam 8 that converges on the sample liquid 7 in the sheath flow portion 9, so that the nano sample particles are excited to emit scattered light signals and fluorescence signals;
[0045] A light-collecting objective lens 1, wherein the object focus of the light-collecting objective lens 1 is aligned with the light source of the scattered light signal and the fluorescent signal;
[0046] A detector 2, the detector 2 is used to receive the optical signal transmitted by the light-collecting objective lens 1, and complete the conversion and detection of the optical signal;
[0047] An adjusting mechanism, wherein the adjusting mechanism automatically adjusts the eccentricity and / or tilt and / or focal plane of the light-collecting lens of the light-collecting objective lens 1 according to the optical signal received by the detector 2 .
[0048] The nano-sample particles in the sample liquid 7 pass through the center of the flow chamber in a queue one by one under the focusing effect of the sheath liquid 6. The illumination light beam 8 emitted by the light source converges on the sample liquid 7 in the center of the flow chamber. The nano-sample particles flowing through are excited to emit scattered light signals and fluorescence signals, which are collected by a light-collecting objective lens 1 with a large numerical aperture. The light-collecting objective lens 1 transmits the optical signals to the corresponding detectors 2, and finally the detector 2 completes the conversion and detection of the optical signals.
[0049] It should be noted that the nanoparticles should flow through the object focus of the light-collecting objective lens 1. When an eccentric deviation occurs between the nano-sample particles and the focus of the light-collecting objective lens 1, the adjustment mechanism automatically adjusts the eccentricity and / or tilt and / or focal plane of the light-collecting lens of the light-collecting objective lens 1 according to the optical signal received by the detector 2, so as to ensure that the object focus is accurately aligned with the signal light source.
[0050] like Figure 1 As shown, in some embodiments, the adjustment mechanism includes a first translation stage 4, a second translation stage 5 and a rotating stage 3, the first translation stage 4 and the second translation stage 5 are orthogonally distributed, the first translation stage 4 is used to correct the eccentric deviation of the light-collecting objective lens 1, the second translation stage 5 is used to correct the defocus deviation of the light-collecting objective lens 1, and the rotating stage 3 is used to correct the tilt deviation of the light-collecting objective lens 1. When the nano-sample particles and the focus of the light-collecting objective lens 1 have an eccentric deviation, the first translation stage 4 can automatically correct the eccentric deviation through the feedback of the optical signal; when the nano-sample particles and the focus of the light-collecting objective lens 1 have a defocus deviation, the second translation stage 5 can automatically correct the defocus deviation through the feedback of the optical signal; when the optical axis of the excited optical signal light beam has a tilt deviation, the rotating stage 3 can automatically correct the tilt deviation through the feedback of the optical signal.
[0051] It should be noted that the orthogonally distributed first translation stage 4 and second translation stage 5 are used to adjust the eccentricity and focal plane respectively. In order to ensure the accuracy of the optical axis, the rotating stage 3 is used to adjust the tilt of the light-collecting objective lens 1.
[0052] like Figure 1 As shown, in some embodiments, the second translation stage 5 is in the same direction as the axis of the light-collecting objective lens 1. When a defocus deviation occurs between the nano-sample particles and the focus of the light-collecting objective lens 1, the second translation stage 5 drives the light-collecting objective lens 1 to move toward or away from the detector 2, thereby completing the correction of the defocus deviation.
[0053] like Figure 1 As shown, in some embodiments, the stroke of the first translation stage 4 covers the fluctuation variation of the optical axis of the optical signal in the X direction, and the first translation stage 4 drives the light-collecting objective lens 1 to produce parallel displacement relative to the detector 2 in the horizontal plane, thereby realizing automatic correction of eccentric deviation, and the stroke range is 1mm to 20mm;
[0054] The stroke of the second translation stage 5 covers the fluctuation variation of the optical axis of the optical signal in the Y direction, where the Y direction is the axis direction of the light-collecting objective lens 1. The second translation stage 5 drives the light-collecting objective lens 1 to move in the horizontal plane toward or away from the detector 2, thereby correcting the defocus deviation. The stroke range is 1 mm to 20 mm.
[0055] The rotation angle of the rotating stage 3 covers the tilt deviation of the optical axis of the optical signal. The rotating stage 3 drives the light-collecting objective lens 1 to rotate in the horizontal plane, thereby correcting the defocus deviation. The rotation angle is 1° to 10°.
[0056] like Figure 1As shown, in some embodiments, the adjustment step of the first translation stage 4 is 0.1 μm to 10 μm; the adjustment step of the second translation stage 5 is 0.1 μm to 10 μm; the adjustment step of the rotating stage 3 is 0.01° to 0.05°, the first translation stage 4 and the second translation stage 5 are both precision translation stages, the first translation stage 4 and the second translation stage 5 respectively drive the light-collecting objective lens 1 to move in directions perpendicular to each other, the rotating stage 3 is a precision rotating stage 3, and the rotating stage 3 drives the light-collecting objective lens 1 to rotate.
[0057] It should be noted that the light-collecting objective lens 1 is mounted on the rotating stage 3 , the rotating stage 3 is mounted on the first translation stage 4 , and the first translation stage 4 is mounted on the second translation stage 5 .
[0058] like Figure 1-Figure 2 As shown, in some embodiments, the numerical aperture of the light-collecting objective lens 1 is between 1 and 1.2, and the working distance of the light-collecting objective lens 1 is between 0.5 mm and 5 mm.
[0059] like Figure 2 As shown, in some embodiments, the illumination light beam 8 is a collimated light beam output by optical fiber or spatial light, and the aperture of the collimated light beam is any value between 0.1 mm and 2 mm, ensuring that the illumination light beam 8 can be collimated and irradiated onto the nano-sample particles in the sample liquid 7, so that the nano-sample particles can be excited to emit scattered light signals and fluorescence signals.
[0060] In some embodiments, the energy density of the spot where the illumination beam 8 converges onto the axial flow is 10 4 ~10 6 W / mm 2 By limiting the energy density of the light spot, the intensity of the scattered light signal and the fluorescence signal is guaranteed.
[0061] In some embodiments, the illumination beam 8 is a monochromatic laser; or, the illumination beam 8 is a plurality of monochromatic lasers of different wavelengths. The illumination beam 8 can be a monochromatic laser, such as a 405nm laser; or it can be a plurality of monochromatic lasers of different wavelengths, such as a combination of any wavelengths such as 375nm, 405nm, 488nm, 561nm, 638nm, etc.
[0062] In some embodiments, the detector 2 may be one of APD, PMT, and MPPC photoelectric sensors, and the target surface diameter of the detector 2 is 1 mm to 10 mm.
[0063] The same or similar parts between the various embodiments in this specification can be referred to each other, and each embodiment focuses on the differences from other embodiments. In particular, for the method embodiment described later, since it corresponds to the system, the description is relatively simple, and the relevant parts can be referred to the partial description of the system embodiment.
[0064] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application shall be based on the protection scope of the claims.
Claims
1. A nano-flow light collecting device, characterized in that: The sample liquid is transferred in the form of front flow focusing, and the light collecting device includes: A sheath flow portion, wherein the sheath flow portion is used for nano sample particles in the sample liquid to pass through under the focusing effect of the sheath liquid; A light source, wherein the light source emits an illumination light beam that converges on the sample liquid in the sheath flow portion, so that the nano sample particles are excited to emit scattered light signals and fluorescence signals; A light-collecting objective lens, wherein the object focus of the light-collecting objective lens is aligned with the light source of the scattered light signal and the fluorescent signal; A detector, the detector is used to receive the optical signal transmitted by the light-collecting objective lens and complete the conversion and detection of the optical signal; An adjusting mechanism is used to automatically adjust the eccentricity and / or tilt and / or focal plane of the light-collecting lens of the light-collecting objective lens according to the optical signal received by the detector.
2. The nano-flow light collecting device according to claim 1, characterized in that: The adjustment mechanism includes a first translation stage, a second translation stage and a rotating stage. The first translation stage and the second translation stage are orthogonally distributed. The first translation stage is used to correct the eccentricity deviation of the light-collecting objective lens, the second translation stage is used to correct the defocus deviation of the light-collecting objective lens, and the rotating stage is used to correct the tilt deviation of the light-collecting objective lens.
3. The nano-flow light collecting device according to claim 2, characterized in that: The second translation stage is in the same direction as the axis of the light-collecting objective lens.
4. The nano-flow light collecting device according to claim 2, characterized in that: The stroke of the first translation stage covers the fluctuation variation of the optical axis of the optical signal in the X direction, and the stroke range is 1 mm to 20 mm; The stroke of the second translation stage covers the fluctuation variation of the optical axis of the optical signal in the Y direction, and the stroke range is 1 mm to 20 mm; The rotation angle of the rotating stage covers the tilt deviation of the optical axis of the optical signal, and the rotation angle is 1° to 10°.
5. The nano-flow light collecting device according to claim 4, characterized in that: The adjustment step length of the first translation stage is 0.1 μm to 10 μm; The adjustment step length of the second translation stage is 0.1 μm to 10 μm; The adjustment step length of the rotating table is 0.01° to 0.05°.
6. The nanoflow light collecting device according to any one of claims 1 to 5, characterized in that: The numerical aperture of the light-collecting objective lens is between 1 and 1.
2.
7. The nanoflow light collecting device according to any one of claims 1 to 5, characterized in that: The illumination light beam is a collimated light beam output by optical fiber or spatial light, and the aperture of the collimated light beam is any value between 0.1 mm and 2 mm.
8. The nanoflow light collecting device according to claim 7, characterized in that: The energy density of the spot where the illumination beam converges onto the axial flow is 10 4 ~10 6 W / mm 2 Magnitude.
9. The nano-flow light collecting device according to claim 8, characterized in that: The illumination light beam is a monochromatic laser; Alternatively, the illumination light beam is a plurality of monochromatic laser beams with different wavelengths.
10. The nanoflow light collecting device according to claim 1, characterized in that: The detector can be one of APD, PMT, and MPPC photoelectric sensors, and the diameter of the detector target surface is 1 mm to 10 mm.