A microfluidic device for terahertz bio-immunological detection

Abstract

The present invention discloses a microfluidic device for terahertz bio-immune detection, which includes a gas source, a pressure reducing valve, an oil-phase container, a sample 1 container, a sample 2 container and a microfluidic chip. The microfluidic chip includes an oil-phase inlet, a sample 1 inlet, a sample 2 inlet, a binary tree, a fusion chamber and a liquid outlet; the gas source is connected to the pressure reducing valve, and the pressure reducing valve is respectively connected to the oil-phase container, the sample 1 container and the sample 2 container. The oil-phase container, the sample 1 container and the sample 2 container are respectively connected to the oil-phase inlet, the sample 1 inlet and the sample 2 inlet. The oil-phase inlet, the sample 1 inlet and the sample 2 inlet are connected to the binary tree, the binary tree is connected to the fusion chamber, a piezoelectric vibrator is arranged in the fusion chamber, and the other end of the fusion chamber is connected to a microchannel for detection and leads to the liquid outlet. The present invention significantly reduces the sample consumption, improves the reaction efficiency, reduces the interference of polar solutions in biological detection, and improves the signal-to-noise ratio of terahertz detection to a certain extent.

Description

Technical Field

[0001] The present invention belongs to the technical field of immunoassay, and particularly relates to a microfluidic device for terahertz bio-immunoassay. Background Art

[0002] Terahertz waves refer to electromagnetic waves with a spectral range between millimeter waves and infrared light, specifically with frequencies between 0.1 and 10 THz. It is a transition region between macroscopic classical theory and microscopic quantum theory, and also a transition region between electronics and photonics. Terahertz waves are thus called the "terahertz gap" in the electromagnetic spectrum. The vibrational and rotational energy levels of many semiconductors, organic substances, and biological macromolecules fall within the spectral range of terahertz waves. In particular, the weak intermolecular / intramolecular forces (such as van der Waals forces and hydrogen bonds) match the energy levels of terahertz waves, which makes terahertz waves highly sensitive to polar molecules such as water. Therefore, terahertz waves can identify different types of pathogenic bacteria by transmitting through the pathogenic bacteria and analyzing their structures.

[0003] Microfluidic chips, also known as laboratories on chips, are chips that allow precise manipulation of trace amounts of fluids in microtubes at the micrometer scale and have performed various functions of traditional physical, chemical, or biological experiments on micrometer-scale chips. Microfluidic chips have become a powerful tool for studying biological systems at single-cell resolution. At the same time, microfluidic chips can not only be widely used to control the generation of droplets but also be used for molecular determination in biochemistry. By controlling trace amounts of fluids in microchannels, microfluidic chips significantly reduce the sample consumption, improve the reaction efficiency, reduce the interference of polar solutions in biological detection, and to a certain extent improve the signal-to-noise ratio of terahertz detection. Summary of the Invention

[0004] In order to overcome the deficiencies of the prior art, the present invention provides a microfluidic device for terahertz bio-immunoassay, including a gas source, a pressure reducing valve, an oil-phase container, a sample 1 container, a sample 2 container, and a microfluidic chip. The microfluidic chip includes an oil-phase inlet, a sample 1 inlet, a sample 2 inlet, a binary tree, a fusion chamber, and a liquid outlet; the gas source is connected to the pressure reducing valve, and the pressure reducing valve is respectively connected to the oil-phase container, the sample 1 container, and the sample 2 container. The oil-phase container, the sample 1 container, and the sample 2 container are respectively connected to the oil-phase inlet, the sample 1 inlet, and the sample 2 inlet. The oil-phase inlet, the sample 1 inlet, and the sample 2 inlet are connected to the binary tree, the binary tree is connected to the fusion chamber, the fusion chamber is provided with a piezoelectric vibrator, and the other end of the fusion chamber is connected to a microchannel for detection and leads to the liquid outlet. The present invention integrates multi-phase sample processing and detection on a single microfluidic chip, significantly reducing the sample consumption, improving the reaction efficiency, reducing the interference of polar solutions in biological detection, and to a certain extent improving the signal-to-noise ratio of terahertz detection.

[0005] The technical solution adopted by the present invention to solve its technical problems is as follows:

[0006] A microfluidic device for terahertz bio-immunodetection, comprising a gas source, a pressure reducing valve, an oil-phase container, a sample 1 container, a sample 2 container and a microfluidic chip;

[0007] The microfluidic chip includes an oil-phase inlet, a sample 1 inlet, a sample 2 inlet, a binary tree, a piezoelectric oscillator, a fusion chamber and a liquid outlet;

[0008] The gas outlet of the gas source is communicated with the gas inlet of the pressure reducing valve; the gas outlet of the pressure reducing valve is respectively communicated with the gas inlets of the oil-phase container, the sample 1 container and the sample 2 container;

[0009] The liquid outlet of the oil-phase container is communicated with the oil-phase liquid inlet of the microfluidic chip; the liquid outlet of the sample 1 container is communicated with the sample 1 inlet of the microfluidic chip, and the liquid outlet of the sample 2 container is communicated with the sample 2 inlet of the microfluidic chip;

[0010] The oil-phase inlet, the sample 1 inlet and the sample 2 inlet are connected by a microchannel, and the other end of the microchannel is communicated with the inlet of the binary tree;

[0011] The outlet of the binary tree is communicated with the fusion chamber, and a piezoelectric oscillator is arranged in the fusion chamber to generate vibration under the action of an electric field;

[0012] The fusion chamber is communicated with the liquid outlet by a microchannel.

[0013] A microfluidic method for terahertz bio-immunodetection, comprising the following steps:

[0014] Step 1: The gas source passes through the pressure reducing valve and enters the oil-phase container, the sample 1 container and the sample 2 container filled with liquid, and a gas driving pressure is formed in the oil-phase container, the sample 1 container and the sample 2 container;

[0015] Step 2: As the gas driving force increases, the liquids in the oil-phase container, the sample 1 container and the sample 2 container enter the microchannel through the oil-phase inlet, the sample 1 inlet and the sample 2 inlet, wherein the oil phase is the continuous phase, the two samples are the discrete phases, and sample 1 and sample 2 are fused at the end of the channel and cut by the oil phase to form separate droplets;

[0016] Step 3: The droplets flow towards the binary tree, are split into smaller droplets in the channel, and flow into the fusion chamber;

[0017] Step 4: The piezoelectric oscillator in the fusion chamber generates vibration under the action of an electric field, promotes the fusion of the droplets, makes the droplets more evenly distributed in the chamber, and flows into the subsequent microchannel in sequence;

[0018] Step 5: The droplets sequentially pass through the terahertz detection region in the microchannel and flow towards the liquid outlet, and the terahertz wave transmits through the sample and is received by the receiving device;

[0019] Step 6: The receiving device receives the attenuated terahertz wave and processes the data to obtain various information of the sample.

[0020] The beneficial effects of the present invention are as follows:

[0021] 1) The microfluidic chip integrates sample preparation and sample detection, eliminating the operation of solution preparation, avoiding the contamination that may be caused by pipetting, and improving the accuracy of detection.

[0022] 2) The microfluidic chip saves the sample usage. Due to the small channels, the samples used for microfluidic chip detection are usually in the microliter level, greatly reducing the actual loss and experimental cost.

[0023] 3) The microfluidic chip has multiple channels, and multiple samples are added simultaneously in one detection, avoiding operations such as sample replacement, and greatly improving the detection efficiency.

[0024] 4) Flow-through detection is adopted, and only one droplet is detected at a time in the detection area, greatly improving the accuracy of terahertz detection. The droplet size is controllable, and the accuracy limit of the device can be gradually approached on this basis. At the same time, the time for waiting for the droplet to flow in is saved. Description of the Drawings

[0025] Figure 1 is a schematic diagram of the microfluidic device of the present invention;

[0026] Figure 2 is a structural diagram of the microfluidic chip.

[0027] Reference numerals: gas source 101, pressure reducing valve 102, oil phase container 103, sample 1 container 104, sample 2 container 105, microfluidic chip 106, oil phase inlet 201, sample 1 inlet 202, sample 2 inlet 203, binary tree 204, piezoelectric vibrator 205, fusion cavity 206, liquid outlet 207. Detailed Embodiments

[0028] The present invention will be further described below in conjunction with the drawings and embodiments.

[0029] To solve the problems of cumbersome and time-consuming sample preparation and low detection efficiency in terahertz wave detection, the present invention provides a multi-channel microfluidic device for terahertz bio-immunological detection, integrating processes such as sample preparation and detection on a single chip, and adopting a multi-channel design to avoid operations such as replacing detection samples, improving the accuracy and efficiency of terahertz wave detection

[0030] The object of the present invention is achieved through the following technical solutions:

[0031] The multi-channel microfluidic device for terahertz bio-immunological detection of the present invention comprises a gas source, a pressure reducing valve, an oil-phase container, a sample 1 container, a sample 2 container and a microfluidic chip.

[0032] The gas outlet of the gas source is communicated with the gas inlet of the pressure reducing valve and the gas inlet of the pressure gauge, and the gas outlet of the pressure reducing valve is respectively communicated with the gas inlets of the oil-phase container, the sample 1 container and the sample 2 container;

[0033] The liquid outlet of the oil-phase container is communicated with the oil-phase liquid inlet of the microfluidic chip, the liquid outlet of the sample 1 container is communicated with the sample 1 liquid inlet of the microfluidic chip, and the liquid outlet of the sample 2 container is communicated with the sample 2 liquid inlet of the microfluidic chip;

[0034] The microfluidic chip comprises an oil-phase inlet, a sample 1 inlet, a sample 2 inlet, a binary tree, a fusion chamber, a piezoelectric oscillator and a liquid outlet. Among them, the oil-phase inlet, the sample 1 inlet and the sample 2 inlet are connected by a microchannel, and the other end of the microchannel is communicated with the inlet of the binary tree;

[0035] The binary tree outlet of the microfluidic chip is communicated with the fusion chamber. The fusion chamber is provided with a piezoelectric oscillator which generates vibration under the action of an electric field, so that adjacent droplets are fused and distributed more uniformly;

[0036] The other end of the fusion chamber of the microfluidic chip is connected to a microchannel and leads to the liquid outlet.

[0037] The operation steps of the present invention are as follows:

[0038] 1) The gas source passes through the pressure reducing valve and enters the oil-phase container, the sample 1 container and the sample 2 container filled with liquid, and a certain gas driving pressure is formed in the oil-phase container, the sample 1 container and the sample 2 container;

[0039] 2) As the gas driving force increases, the liquids in the oil-phase container, the sample 1 container and the sample 2 container enter the microchannel through the oil-phase inlet, the sample 1 inlet and the sample 2 inlet. Among them, the oil phase is the continuous phase, and the two samples are the discrete phases. Sample 1 and sample 2 are fused at the end of the channel and cut by the oil phase to form separate droplets;

[0040] 3) The droplets flow towards the binary tree, are split into smaller droplets in the channel and flow into the fusion chamber;

[0041] 4) The piezoelectric oscillator in the fusion chamber generates vibration under the action of an electric field, promotes the fusion of adjacent droplets, makes the droplets more uniformly distributed in the chamber, and flows into the subsequent microchannel in turn;

[0042] 5) The droplets sequentially pass through the terahertz detection area in the microchannel and flow towards the liquid outlet, and the terahertz wave transmits through the sample and is received by the receiving device;

[0043] 6) The receiving device receives the attenuated terahertz wave and processes the data to obtain various information of the sample.

[0044] Embodiment:

[0045] As Figure 1 and 2 shown, this embodiment consists of a gas source 101, a pressure reducing valve 102, an oil phase container 103, a sample 1 container 104, a sample 2 container 105, and a microfluidic chip 106. The microfluidic chip 106 includes an oil phase inlet 201, a sample 1 inlet 202, a sample 2 inlet 203, a binary tree 204, a piezoelectric oscillator 205, a fusion chamber 206, and a liquid outlet 207. Among them:

[0046] The gas outlet of the gas source 101 is connected to the gas inlet of the pressure reducing valve 102, and the gas outlet of the pressure reducing valve 102 is respectively connected to the gas inlets of the oil phase container 103, the sample 1 container 104, and the sample 2 container 105;

[0047] The liquid outlet of the oil phase container 103 is connected to the oil phase liquid inlet of the microfluidic chip, the liquid outlet of the sample 1 container 104 is connected to the sample 1 liquid inlet 202 of the microfluidic chip, and the liquid outlet of the sample 2 container 105 is connected to the sample 2 liquid inlet 203 of the microfluidic chip;

[0048] The oil phase inlet 201, the sample 1 inlet 202, and the sample 2 inlet 203 are connected by a microchannel, and the other end of the microchannel is connected to the inlet of the binary tree 204;

[0049] The outlet of the binary tree 204 is connected to the fusion chamber, and the fusion chamber 206 is provided with a piezoelectric oscillator 205 that generates vibrations under the action of an electric field;

[0050] The fusion chamber 206 is connected to the liquid outlet 207 by a microchannel.

[0051] Working principle:

[0052] The gas source passes through a pressure reducing valve and enters the oil phase container filled with liquid, the sample 1 container, and the sample 2 container, forming a certain gas driving pressure in the oil phase container, the sample 1 container, and the sample 2 container; as the gas driving force increases, the liquid in the oil phase container, the sample 1 container, and the sample 2 container enters the microchannel through the oil phase inlet, the sample 1 inlet, and the sample 2 inlet. Among them, the oil phase is the continuous phase, and the two samples are discrete phases. Sample 1 and sample 2 fuse at the end of the channel and are cut by the oil phase to form separate droplets; the droplets flow towards the binary tree, are divided into smaller droplets in the channel, and flow into the fusion chamber; the piezoelectric oscillator in the fusion chamber generates vibrations under the action of an electric field, promoting the fusion of adjacent droplets, making the droplets more evenly distributed in the chamber, and flowing into the subsequent microchannel in sequence. The droplets pass through the terahertz detection area in the microchannel in sequence and flow towards the liquid outlet, and the terahertz wave transmits through the sample and is received by the receiving device.

[0053] This embodiment significantly reduces the sample consumption, improves the reaction efficiency, reduces the interference of polar solutions in biological detection, and improves the signal-to-noise ratio of terahertz detection to a certain extent.

Claims

1. A microfluidic device for terahertz bio-immunological detection, characterized in that, It includes a gas source, a pressure reducing valve, an oil phase container, a sample 1 container, a sample 2 container and a microfluidic chip; The microfluidic chip includes an oil phase inlet, a sample 1 inlet, a sample 2 inlet, a binary tree, a piezoelectric oscillator, a fusion chamber and a liquid outlet; The gas outlet of the gas source is communicated with the gas inlet of the pressure reducing valve; the gas outlet of the pressure reducing valve is respectively communicated with the gas inlets of the oil phase container, the sample 1 container and the sample 2 container; The liquid outlet of the oil phase container is communicated with the oil phase liquid inlet of the microfluidic chip; the liquid outlet of the sample 1 container is communicated with the sample 1 inlet of the microfluidic chip, and the liquid outlet of the sample 2 container is communicated with the sample 2 inlet of the microfluidic chip; The oil phase inlet, the sample 1 inlet and the sample 2 inlet are connected by a microchannel, and the other end of the microchannel is communicated with the inlet of the binary tree; The outlet of the binary tree is communicated with the fusion chamber, and a piezoelectric oscillator is arranged in the fusion chamber to generate vibration under the action of an electric field; The fusion chamber is communicated with the liquid outlet by a microchannel.

2. A detection method using the microfluidic device as described in claim 1, characterized in that, It includes the following steps: Step 1: The gas from the gas source enters the oil phase container, the sample 1 container and the sample 2 container filled with liquid through the pressure reducing valve, and a gas driving pressure is formed in the oil phase container, the sample 1 container and the sample 2 container; Step 2: As the gas driving force increases, the liquids in the oil phase container, the sample 1 container and the sample 2 container enter the microchannel through the oil phase inlet, the sample 1 inlet and the sample 2 inlet. Among them, the oil phase is the continuous phase, the two samples are the discrete phases, and sample 1 and sample 2 are fused at the end of the channel and cut by the oil phase to form separate droplets; Step 3: The droplets flow to the binary tree, are split into smaller droplets in the channel, and flow into the fusion chamber; Step 4: The piezoelectric oscillator in the fusion chamber generates vibration under the action of an electric field, promotes the fusion of the droplets, makes the droplets more evenly distributed in the chamber, and flows into the subsequent microchannel in turn; Step 5: The droplets sequentially pass through the terahertz detection area in the microchannel and flow to the liquid outlet, and the terahertz wave transmits through the sample and is received by the receiving device; Step 6: The receiving device receives the attenuated terahertz wave and processes the data to obtain various information of the sample.

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