Dot matrix hybridization energy source system for single cell detection

Abstract

The application relates to the technical field of cell detection, and specifically discloses a dot-matrix mixed-wave co-polymerization energy source system for single-cell detection, which comprises a mixed-wave length LED dot-matrix module, an active tunable optical focusing module, a closed-loop temperature control and deformation driving module and a biological chip bearing module. The optical focusing module comprises a variable-position Fresnel lens and a bimetallic thermal composite connected with the variable-position Fresnel lens. The temperature of the composite is actively adjusted through the temperature control module, controllable bending deformation is induced by using the difference between the thermal expansion coefficients of the two layers of metal, and the deflection angle of the lens is accurately adjusted. The system forms a closed-loop control based on the feedback of a working wavelength and an illumination sensor, dynamically compensates the dispersion difference and thermal drift effect of different wavelengths, and ensures that the energy sources of different wavelengths can be stably and accurately focused on the micrometer-level target points of the biological chip. The application has high focusing stability and fast response, and is suitable for the fields of high-precision biological detection such as single-cell protein fixation and gel electrophoresis.

Description

Technical Field

[0001] This invention belongs to the field of cell detection technology, specifically a dot matrix mixing co-concentrating energy source system for single-cell detection. Background Technology

[0002] In biological experiments such as single-cell protein immunoblotting, it is often necessary to use energy sources of different wavelengths to target or activate specifically expressed proteins. Traditional methods often employ devices with different wavelengths for segmented experiments, requiring multiple experimental steps, which is time-consuming and unstable. Existing technologies also include solutions using ultra-high precision multidimensional motion components to carry devices with different wavelengths, but these have the following problems:

[0003] 1. The motion device is expensive and bulky;

[0004] 2. It needs to be operated in a constant temperature and humidity environment, and the thermal field affects the long experimental intervals;

[0005] 3. Corrosive gases in the experimental environment can easily damage moving components;

[0006] 4. Multiple sets of experiments are time-consuming and conducted under different environmental parameters, affecting the consistency and accuracy of the experiments.

[0007] Therefore, there is an urgent need for an energy source system that can achieve multi-wavelength adaptive confocalization, has a compact structure, fast response, and is suitable for complex experimental environments. Summary of the Invention

[0008] To address the aforementioned technical problems, this invention aims to provide a dot-matrix mixed-wave cofocusing energy source system for single-cell detection, thereby solving the technical problems of multi-wavelength light sources being unable to cofocus, thermal drift affecting focusing stability, and the complex structure, slow response, and high cost of traditional devices.

[0009] To achieve the above objectives, this invention provides a dot-matrix mixing co-focusing energy source system for single-cell detection, the core of which lies in combining optical focusing with controllable thermodynamic deformation, including:

[0010] Mixed-wavelength LED matrix module, used to emit light of multiple predetermined wavelengths;

[0011] An active tunable optical focusing module is located below the optical path of the mixed-wavelength LED dot matrix module, and is used to receive and focus the light onto the target point;

[0012] A closed-loop temperature control and deformation driving module is connected to the active tunable optical focusing module and is used to actively control its deformation.

[0013] And a biochip carrier module for fixing the biochip, wherein the target point of the biochip is located within the focusing area of ​​the active tunable optical focusing module;

[0014] The closed-loop temperature control and deformation driving module drives the active tunable optical focusing module to generate regular deformation according to the working wavelength of the mixed wavelength LED dot matrix module or the system operating conditions, so as to dynamically adjust the optical path and ensure that light energy of different wavelengths can be accurately focused on the target point.

[0015] Furthermore, the active tunable optical focusing module includes:

[0016] Displacement Fresnel lens;

[0017] A thermosensitive composite is fixedly connected to the upper end or one side of the displaced Fresnel lens. The thermosensitive composite is composed of a first metal layer and a second metal layer with different coefficients of thermal expansion.

[0018] The closed-loop temperature control and deformation driving module controls the temperature of the thermosensitive composite, causing it to bend due to the difference in thermal expansion between the first metal layer and the second metal layer, thereby driving the displacement Fresnel lens to deflect.

[0019] Specifically, the first metal layer is an aluminum alloy layer, and the second metal layer is an iron-nickel alloy layer.

[0020] Furthermore, the closed-loop temperature control and deformation drive module includes:

[0021] A heat sink is located above the mixed-wavelength LED matrix module and dissipates heat from it.

[0022] Heat conduction lines, integrated within the first metal layer, are used to regulate the temperature of the heat conduction fluid;

[0023] A temperature sensor is installed on the heat conduction pipeline or the active tunable optical focusing module to monitor the temperature;

[0024] The controller is electrically connected to the temperature sensor and the mixed-wavelength LED matrix module;

[0025] The controller adjusts the temperature of the heat transfer fluid flowing through the heat transfer pipeline based on the current operating wavelength and / or the feedback signal from the temperature sensor, thereby controlling the deformation of the active tunable optical focusing module.

[0026] The controller has a pre-stored mapping table between different operating wavelengths and target temperature settings. When a change in operating wavelength is detected, the corresponding target temperature is automatically called and the closed-loop feedback control is started.

[0027] Furthermore, the closed-loop temperature control and deformation driving module also includes a light intensity sensor, which is set near the target point of the biochip or the optical path monitoring point to detect the light intensity reaching the target point in real time.

[0028] The controller is electrically connected to the light intensity sensor, receives the light intensity signal and forms a closed-loop feedback with the temperature signal, and maintains the light intensity reaching the target point at the maximum value or within a preset range by adjusting the temperature of the thermally conductive liquid.

[0029] Furthermore, the mixed-wavelength LED dot matrix module includes multiple LED chips that emit different wavelengths, with the wavelength range being between 200nm and 2000nm; the LED chips are mixed and arranged to form a uniform dot matrix and mounted on an aluminum substrate, and each wavelength LED chip can be driven independently.

[0030] Specifically, the biochip carrier module includes an electrophoresis tank, and the biochip is a gel electrophoresis chip or a single-cell protein immobilization chip, with the target being the lanes or protein immobilization sites on the chip.

[0031] The energy focusing control method of the lattice mixing co-focusing energy source system of the present invention includes the following steps:

[0032] S1: Start the system and drive the LED chips of a specific wavelength in the mixed-wavelength LED matrix module to emit light according to the detection requirements;

[0033] S2: The closed-loop temperature control and deformation drive module obtains the corresponding target temperature setpoint based on the specific wavelength;

[0034] S3: Adjust the temperature of the thermally conductive liquid so that the active tunable optical focusing module reaches or approaches the target temperature, thereby generating a predetermined deformation and deflection;

[0035] S4: Real-time monitoring of light intensity reaching the target site of the biochip;

[0036] S5: Based on the monitored light intensity, the temperature of the thermally conductive liquid is finely adjusted through closed-loop feedback until the light intensity reaches the peak or meets the preset threshold, thus completing the focusing calibration.

[0037] In step S5, when the system detects a change in operating wavelength, a change in ambient temperature, or an intensity attenuation exceeding the tolerance, steps S2 to S5 are automatically re-executed to achieve dynamic real-time calibration.

[0038] The dot-matrix confocal energy source system of this invention overcomes the technical bottlenecks of existing single-cell detection energy source systems in terms of multi-wavelength confocalization, thermal stability, and automation by innovatively integrating a multi-wavelength LED array, active deformation optical elements, and closed-loop temperature control technology. Its beneficial effects are specifically reflected in the following aspects:

[0039] 1. This invention transforms the problem of optical focus adjustment into a problem of thermodynamic deformation control. By precisely controlling the temperature of the bimetallic thermosensitive composite, the displacement Fresnel lens is driven to produce a micron-level angle deflection. This directly compensates for the refraction angle difference of different wavelengths from the physical optical path. Any working wavelength in the range of 200nm-2000nm can be precisely focused on the same physical target point of the biochip through temperature control, achieving a breakthrough from "one target, multiple focal points" to "one target, confocal focus".

[0040] 2. The energy source of this invention has extremely high focusing stability: The system has a built-in dual-loop feedback mechanism consisting of a temperature sensor and a light intensity sensor. The closed-loop feedback control effectively offsets the effects of factors such as LED self-heating and ambient temperature fluctuations, providing a continuous and stable energy supply environment for single-cell experiments that last for several hours.

[0041] 3. The energy source system of this invention features a simplified, compact, and highly reliable structure. The entire focusing mechanism eliminates complex multi-lens groups, linear guides, precision lead screws, and other moving parts, consisting only of a core unit of a "bimetallic composite + Fresnel lens," resulting in an extremely compact structure. This allows the entire energy source system to be easily integrated into the limited optical path space of existing microscopes, flow cytometers, or microfluidic chip detection platforms.

[0042] 4. The simplified mechanical structure of the energy source system of this invention directly leads to a significant reduction in manufacturing costs. Simultaneously, due to the absence of easily worn moving parts, the system exhibits an extremely low failure rate during long-term use and demonstrates stronger resistance to corrosive gas environments, making it particularly suitable for stable operation in complex environments such as biochemical laboratories, with low maintenance requirements. Attached Figure Description

[0043] To more clearly illustrate the technical solution of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0044] Figure 1 This is a schematic cross-sectional view of the overall structure of the lattice mixing co-concentrating energy source system according to an embodiment of the present invention;

[0045] Figure 2 A schematic diagram of the illumination of a 200nm wavelength dot matrix hybrid co-concentrating energy source system;

[0046] Figure 3 A schematic diagram of the illumination of a 400nm wavelength dot matrix hybrid co-concentrating energy source system;

[0047] In the diagram: 1-Heat sink, 2-Heat conduction pipeline, 3-Mixed wavelength LED dot matrix module, 4-Aluminum substrate, 5-Second metal layer, 6-First metal layer, 7-Displacement Fresnel lens, 8-Biochip, 9-Electrophoresis tank. Detailed Implementation

[0048] The technical solutions in the embodiments of the invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0049] like Figure 1 As shown, in a preferred embodiment of the present invention, a dot matrix mixing co-concentrating energy source system for single-cell detection comprises, from top to bottom, a heat dissipation layer, a light source layer, a focusing layer, and a sample layer.

[0050] Heat dissipation and temperature control layer: Heat sink 1 is a forced air-cooled heat sink 1, located on the mixed wavelength LED matrix module 3 and dissipating heat for it;

[0051] Light source layer: Below the heat sink is an aluminum substrate 4 tightly bonded with thermal grease. Multiple LED chips are soldered onto the upper surface of the aluminum substrate 4 using SMT technology. These chips emit ultraviolet light of different wavelengths from 200nm to 2000nm, and are arranged alternately to form a uniform light-emitting array. Each wavelength series of LEDs is controlled by an independent constant current drive circuit.

[0052] Focusing layer: This is the core functional layer of the invention. Below the aluminum substrate 4, a heat-insulating gasket (to prevent direct interference from LED heat) secures the thermistor composite. This composite is formed by bonding a first metal layer 6 (upper 0.5mm thick 6061 aluminum alloy sheet) and a second metal layer 5 (lower 0.3mm thick Invar alloy (iron-nickel alloy) sheet) using a high-temperature diffusion welding process. A Fresnel lens 7 made of ultraviolet quartz material is bonded and fixed to the center of the lower surface of the composite using low-stress UV-curable adhesive. A section of the heat conduction conduit 2 is designed to be embedded within the aluminum alloy layer of the composite to achieve efficient heat exchange.

[0053] Sample Layer: Below the focusing layer is an openable sample chamber containing an electrophoresis tank 9. During detection, a glass-based biochip 8 is placed and positioned within the tank. Microchannels are etched onto the biochip 8, with the target detection area (target point) located at the center of the microchannels. A miniature silicon photodiode illuminance sensor is ingeniously positioned on the lower side of the biochip 8, receiving a tiny fraction of the light signal scattered from the target point via a miniature mirror, thus indirectly but accurately reflecting the light intensity at the target point.

[0054] Example of work process:

[0055] Assume the experimental procedure requires pre-curing using a 200nm wavelength. After system startup:

[0056] The controller turns on the 200nm LED array and turns off the other wavelength LEDs.

[0057] The controller queries the internal mapping table and sets the target temperature of the heat transfer fluid to 45℃.

[0058] The temperature control system operates, heating and stabilizing the thermally conductive liquid at approximately 45°C. Heat is transferred to the composite material, causing the aluminum alloy layer to expand more than the Invar alloy layer (iron-nickel alloy layer 5). The composite material then bends slightly downwards (towards the Invar alloy side), causing the Fresnel lens 7 to produce a small positive depression angle.

[0059] The illuminance sensor begins reading, with an initial value of I0. The controller initiates the "maximum light intensity" search algorithm, fine-tuning the heat transfer fluid temperature around 45℃ in steps of 0.1℃. It is assumed that the sensor reading reaches its maximum value, I_max, when the temperature is adjusted to 45.3℃.

[0060] The controller locks the current temperature of 45.3℃ as the optimal temperature under the current operating conditions, and the system enters a stable working state, continuously and precisely focusing 280nm light energy onto the chip swimlane.

[0061] After 30 minutes, the program needs to switch to the 400nm wavelength for the next reaction step. The controller turns off the 280nm LED, turns on the 400nm LED, and immediately switches the target temperature of the thermal conductivity liquid to the corresponding 38℃ in the mapping table.

[0062] The system repeats the search process of steps 3-5 to quickly find the optimal temperature (e.g., 38.5℃) at a wavelength of 400nm and then re-stabilizes the focus.

[0063] Through the above methods, the present invention achieves fully automatic and high-precision energy focusing control for different wavelengths and different working stages, which greatly improves the repeatability, accuracy and automation of single-cell detection.

[0064] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A dot-matrix mixing co-concentrating energy source system for single-cell detection, characterized in that, include: A mixed-wavelength LED matrix module (3) is used to emit light of multiple predetermined wavelengths; An active tunable optical focusing module is located below the optical path of the mixed-wavelength LED dot matrix module (3) and is used to receive and focus light onto the target point. A closed-loop temperature control and deformation driving module is connected to the active tunable optical focusing module and is used to actively control its deformation. And a biochip carrier module for fixing the biochip (8), wherein the target point of the biochip (8) is located in the focusing area of ​​the active tunable optical focusing module; The closed-loop temperature control and deformation driving module drives the active tunable optical focusing module to generate regular deformation according to the working wavelength of the mixed wavelength LED dot matrix module (3) so as to dynamically adjust the optical path and enable light energy of different wavelengths to be accurately focused on the target point.

2. The dot matrix mixing co-concentrating energy source system for single-cell detection according to claim 1, characterized in that, The active tunable optical focusing module includes: Displacement Fresnel lens (7); A thermosensitive composite is fixedly connected to the upper end or one side of the displaced Fresnel lens (7). The thermosensitive composite is composed of a first metal layer (6) and a second metal layer (5) with different coefficients of thermal expansion. The closed-loop temperature control and deformation driving module controls the temperature of the thermosensitive composite, causing it to bend due to the difference in thermal expansion between the first metal layer (6) and the second metal layer (5), thereby causing the displacement Fresnel lens (7) to deflect.

3. A dot-matrix mixing co-concentrating energy source system for single-cell detection according to claim 2, characterized in that, The first metal layer (6) is an aluminum alloy layer, and the second metal layer (5) is an iron-nickel alloy layer.

4. A dot-matrix mixing co-concentrating energy source system for single-cell detection according to claim 2, characterized in that, The closed-loop temperature control and deformation drive module includes: A heat sink (1) is located above the mixed-wavelength LED matrix module (3) and dissipates heat from it; The heat conduction pipeline (2) is integrated into the first metal layer (6) and is used to regulate the temperature of the heat conduction fluid; A temperature sensor is installed on the heat conduction pipeline (2) or the active tunable optical focusing module to monitor the temperature; The controller is electrically connected to the temperature sensor and the mixed-wavelength LED matrix module (3); The controller adjusts the temperature of the heat transfer fluid flowing through the heat transfer line (2) according to the current operating wavelength and / or the feedback signal from the temperature sensor, so as to control the deformation of the active tunable optical focusing module.

5. A dot-matrix mixing co-concentrating energy source system for single-cell detection according to claim 4, characterized in that, The closed-loop temperature control and deformation drive module also includes a light intensity sensor, which is set near the target point or the optical path monitoring point of the biochip (8) to detect the light intensity reaching the target point in real time. The controller is electrically connected to the light intensity sensor, receives the light intensity signal and forms a closed-loop feedback with the temperature signal, and maintains the light intensity reaching the target point at the maximum value or within a preset range by adjusting the temperature of the thermally conductive liquid.

6. A dot-matrix mixing co-concentrating energy source system for single-cell detection according to claim 1, characterized in that, The mixed-wavelength LED dot matrix module (3) includes multiple LED chips that emit different wavelengths, with a wavelength range between 200nm and 2000nm; the LED chips are mixed and arranged to form a uniform dot matrix and are mounted on an aluminum substrate (4), and each wavelength LED chip can be driven independently.

7. A dot-matrix mixing co-concentrating energy source system for single-cell detection according to claim 1, characterized in that, The biochip carrier module includes an electrophoresis tank (9), and the biochip (8) is a gel electrophoresis chip or a single-cell protein immobilization chip, the target of which is the lane or protein immobilization site on the chip.

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