CN110170183A - A kind of production method of miniature chromatography column, miniature chromatography column and minitype gas analysis system - Google Patents

Abstract

The present invention provides a kind of production method of miniature chromatography column, miniature chromatography column and minitype gas analysis system, the production method includes: A, using silicon materials production micro-compliant mechanism substrate；B, in the fluid channel of the bottom of glass plate production square spiral shape structure；C, production there is the bottom of the glass plate of the fluid channel of square spiral shape structure to be bonded with the upper surface of the substrate, to form miniature chromatography column.By upper, the above-mentioned production method of the application is the production method of pioneering chromatography column, is conducive to make small chromatography column, to be conducive to the micromation of gas detection analytical equipment, to be advantageously implemented the easily analysis detection to gas.

Description

Manufacturing method of micro-chromatographic separation column, micro-chromatographic separation column and micro-gas volume analysis system

technical field

The invention relates to the field of gas detection and analysis, and particularly relates to a manufacturing method of a miniature chromatographic separation column, a miniature chromatographic separation column and a miniature gas analysis system.

Background technique

The detection of organic volatile gases, such as the detection of disease markers and environmental pollutants, plays a vital role in the early detection of some major diseases, including diabetes and renal failure, and the supervision and prevention of environmental pollution. Traditional gas detection methods are mostly laboratory-based large-scale analytical instruments, such as gas chromatography-mass spectrometers, etc. Although these instruments can accurately detect the composition and content of mixed gases, these methods are complex, time-consuming, and bulky. It is too large to realize on-site monitoring. Because the volume of the detector part of the traditional gas chromatograph is too large, the miniaturization development of the whole gas analysis system is restricted. In recent years, the miniaturization of the detector part of the gas chromatograph has been carried out. But no real progress has been made yet. Therefore, there is an urgent need to solve or partially solve the above technical problems. In order to facilitate the realization of convenient gas analysis and detection.

SUMMARY OF THE INVENTION

In view of this, the present application provides a manufacturing method of a micro chromatographic separation column, a micro chromatographic separation column and a micro gas analysis system, which are beneficial to realize miniaturization and convenient gas detection.

The application provides a method for making a microchromatographic separation column, characterized in that it includes:

A. Use silicon material to make micro-chromatographic column base;

B. Making a micro-channel with a square helical structure at the bottom of a glass plate;

C. Bond the bottom of the glass plate with the micro-flow channel with the square helical structure and the upper surface of the substrate to form a micro-chromatographic separation column.

From the above, the microfluidic chromatographic separation column of the present application is manufactured into a square helical structure, which can maximize the separation efficiency of the chromatographic column, and the glass plate (which can be a Pyrex glass plate) Sealed with base plate. The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, to the miniaturization of the gas detection and analysis device, and to the realization of convenient gas analysis and detection.

Preferably, the step B includes:

B1. Through photolithography and deep silicon etching process, a micro-channel with a square spiral structure is manufactured;

B2. Modification of the stationary phase is performed on the inner surface of the microfluidic channel.

Preferably, the step B2 includes:

B21. Activating the inner surface of the microchannel by octamethylcyclotetrasiloxane;

B22. 100% polydimethylsiloxane is modified on the inner surface of the microfluidic channel by dynamic coating;

B23. Crosslinking the stationary phase to ensure the stability of the stationary phase;

B24, heating and aging for 4 hours.

From the above, it is beneficial to better realize the separation of the mixed gas.

The application also provides a micro-chromatographic separation column made based on the above-mentioned preparation method, characterized in that it includes:

base,

A glass plate, the bottom of which is etched with a micro-flow channel of a square helical structure;

Wherein, the bottom of the glass plate is bonded with the upper surface of the substrate.

From the above, the microfluidic chromatographic separation column of the present application is manufactured into a square helical structure, which can maximize the separation efficiency of the chromatographic column, and the glass plate (which can be a Pyrex glass plate) Sealed with bottom plate to make tiny chromatographic separation columns. The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, so as to facilitate the miniaturization of a gas detection and analysis device.

Based on the above-mentioned micro chromatographic separation column, the present application also provides a micro gas analysis system, comprising:

A sample injection system, comprising: a sample injection port and a sample injection pump; wherein, the sample injection pump is communicated with the sample injection port through a gas pipeline to provide power support for sample injection;

a carrier gas subsystem, including a pressure control valve, a pressure gauge and a flow meter, for precise control of the gas flow, and connected with the outlet of the inlet sub-system for loading the sample into the micro-chromatographic separation column;

Wherein, the micro-chromatographic separation column is connected with the inlet sub-system and the carrier gas subsystem, and is used to separate the sample;

The bulk acoustic wave resonator array is connected to the outlet of the micro chromatographic column, and is used for identifying and detecting the gas.

From the above, the micro gas analysis system of the present application performs gas separation through a micro chromatographic column and gas identification and detection through a bulk acoustic wave resonator, so as to realize convenient gas detection.

Preferably, the bulk acoustic wave resonator array comprises:

a support plate, on which a bulk acoustic wave resonator array region is arranged;

A glass micro-flow channel is arranged on the bulk acoustic wave resonator array area; wherein, the two ends of the glass micro-flow channel are respectively provided with an air inlet and an air outlet; wherein, the air inlet and the air outlet are Quartz capillaries are respectively connected to the upper parts for gas connection;

Wherein, the air inlet is connected to the outlet of the micro chromatographic column through the quartz capillary; the air outlet is connected to a waste gas recovery device through the quartz capillary.

From the above, the arrangement of the above-mentioned glass micro-flow channel is beneficial to increase the contact between the gas and the bulk acoustic wave resonator, and is beneficial to better gas detection. The arrangement of the support plate is favorable for arranging the resonators thereon in the form of an array, and the support plate is provided with ventilation holes, which is favorable for the passage of gas.

Preferably, in the bulk acoustic wave resonator array, different bulk acoustic wave resonators are decorated with polymers capable of adsorbing different types of measured gases.

From the above, by modifying different bulk acoustic wave resonators with different polymers, the identification and detection of different gases in the unseparated mixed gas in the chromatographic column is facilitated.

Preferably, the carrier gas subsystem includes:

The nitrogen cylinder, the pressure control valve, the pressure gauge and the flow meter are connected in sequence.

From the above, the pressure of the carrier gas output from the nitrogen cylinder 6 can be controlled by setting the pressure control valve and the pressure gauge, and the flow rate of the carrier gas can be controlled by setting the flow meter.

Preferably, the system further includes:

Connected to the BAW resonator array is a network analyzer for sweeping measurements over a wide frequency band to determine network parameters and display signals.

Preferably, the system further includes:

Temperature control and digital display for temperature control of the environment in which the micro-columns are located.

From the above, the temperature control and the digital display are provided, and the detection temperature can be controlled to better realize the detection of the gas.

To sum up, the manufacturing method of the micro-chromatographic separation column provided by this application, the chromatographic separation column is manufactured into a square spiral structure, this structure can maximize the separation efficiency of the chromatographic column, and the glass plate ( Can be a Pyrex glass plate) sealed to the bottom plate. The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, so as to facilitate the miniaturization of a gas detection and analysis device. The analysis system provided by the present application can conveniently realize the separation and detection of the mixed gas. The whole system has the characteristics of miniaturization, simplicity, high identification efficiency and compatibility with semiconductor technology. And the bulk acoustic wave resonator device of the present application can also be set as an array-type bulk acoustic wave resonator, and different bulk acoustic wave resonators are decorated with polymers with the function of adsorbing different types of gas to be tested, so that the traditional BAW resonator can be realized. Qualitative and quantitative identification detection of binary gas mixtures with overlapping peak positions that cannot be identified by a single gas chromatographic column.

Description of drawings

Fig. 1 is the schematic flow sheet of the preparation method of the microchromatographic separation column provided in the embodiment of the present application;

Fig. 2 is the structural representation of the microchromatographic separation column provided in the embodiment of the present application;

Fig. 3 is the flow chart of the chromatographic column stationary phase modification provided in the embodiment of the present application;

FIG. 4 is a schematic diagram of the principle of gas detection by a bulk acoustic wave resonator provided in an embodiment of the present application.

5 is a schematic structural diagram of a bulk acoustic wave resonator and a glass microchannel above it provided by an embodiment of the present application;

FIG. 6 is a schematic structural diagram of a micro gas analysis system provided by an embodiment of the present application.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, but not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art fall within the protection scope of the present invention.

Example 1

As shown in Figure 1, the manufacture method of a kind of micro-chromatographic separation column provided by the application comprises:

S101, using a silicon material to make a micro-chromatographic column substrate;

S102, making a micro-channel with a square spiral structure at the bottom of a glass plate;

S103, modifying the stationary phase on the inner surface of the microfluidic channel. include:

S1031, through photolithography and deep silicon etching process, a micro flow channel with a square helical structure is manufactured; further, in order to better realize the separation of mixed gas, the manufactured micro chromatographic column needs to be subjected to appropriate stationary phase purification. retouch. Steps S1022 to S1025 are included.

S1032, activating the inner surface of the microfluidic channel by octamethylcyclotetrasiloxane;

S1033, modifying the inner surface of the microfluidic channel with 100% polydimethylsiloxane by dynamic coating;

S1034, cross-linking the stationary phase to ensure the stability of the stationary phase;

S1035, high temperature aging for 4 hours to complete the entire coating process. It is beneficial to better realize the separation of mixed gas.

S103, bonding the bottom of the glass plate with the microfluidic channel with the square helical structure and the upper surface of the substrate to form a microfluidic chromatographic separation column.

The micro-channel chromatographic separation column of the present application is manufactured into a square helical structure, which can maximize the separation efficiency of the chromatographic column. The glass plate (which can be a Pyrex glass plate) is sealed with the bottom plate by means of bonding. . The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, so as to facilitate the miniaturization of a gas detection and analysis device.

Embodiment 2

As shown in Figure 2, based on the above-mentioned micro-chromatographic separation column, the present application also provides a micro-chromatographic separation column made based on the above-mentioned production method, comprising:

Substrate 201,

The glass plate 203, the bottom of which is etched with micro-channels of square helical structure;

Wherein, the bottom of the glass plate is bonded with the upper surface of the substrate.

Specifically, the micro-chromatographic column base 201 is made of silicon material through photolithography and deep silicon etching processes to form a square helical structure. This structure can maximize the separation efficiency of the chromatographic column. The Hexer glass plate 203 is sealed with the bottom plate, and capillary glass tubes 202 are inserted into the gas inlet and outlet to connect with the front and rear gas paths.

Similar to Example 1, in order to better realize the separation of mixed gas, the fabricated micro-chromatographic column needs to be modified with appropriate stationary phase. In this embodiment, as shown in Figure 3, S301, use octamethylcyclotetrasiloxane to activate the surface, and then S302, select dynamic coating to modify 100% polydimethylsiloxane On the side wall of the chromatographic column, then S303, the stationary phase is cross-linked to ensure the stability of the stationary phase, and finally, S304, high temperature aging for 4 hours, to complete the entire coating process. The micro-channel chromatographic separation column of the present application is manufactured into a square helical structure, which can maximize the separation efficiency of the chromatographic column. The glass plate (which can be a Pyrex glass plate) is sealed with the bottom plate by means of bonding. , to make tiny chromatographic separation columns. The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, so as to facilitate the miniaturization of a gas detection and analysis device.

Embodiment 3

Based on the above-mentioned micro-chromatographic separation column, as shown in FIG. 6, a micro-gas analysis system provided by the present application is used to detect organic volatile gases (for example, alkanes existing in liquid form at room temperature; aromatics related to environmental pollution) Compounds; alcohols and aldehydes contained in human exhaled breath; aromas emitted by fruits and crops at different growth stages; gas markers of some major diseases; simulants of chemical warfare agents, etc.). Specifically include:

The sample injection port 104 and the injection pump 105 which are connected by gas are connected in series through the pipeline.

The nitrogen cylinder 101 , the pressure control valve, the pressure gauge 102 , and the flow meter 103 are connected in series in sequence through the pipeline.

A micro-chromatographic column 107 for gas separation, a bulk acoustic wave resonator array 109, and a network analyzer 110 for signal driving and display of the bulk acoustic wave resonator array 109. The timing switch 108 is used to control the gas detection according to the set time.

The temperature control and digital display 6 for controlling the temperature of the environment where the micro-chromatographic column 107 is located can better realize gas separation by controlling the temperature of the micro-chromatographic column 107 . Among them, the optimal setting temperature is 100°C.

In order to explain the present application more clearly, some of the above-mentioned components are described in detail below:

The nitrogen cylinder 101 , the pressure control valve, the pressure gauge 102 and the flow meter 103 constitute a carrier gas subsystem. The nitrogen cylinder 101 has high-pressure nitrogen (which can be stored in the nitrogen cylinder 101 in liquid form), and the nitrogen released by the nitrogen cylinder 101 is used as the carrier gas; the pressure of the output carrier gas can be controlled by setting the pressure control valve and the pressure gauge 102, preferably set as The pressure of 15psi; the flow rate of the output carrier gas can be controlled by setting the flow meter 103, and the preferred setting is the flow rate of 20ml/min.

The bulk acoustic wave resonator array 109 is used to further detect the gas separated by the micro-chromatographic column 107 to obtain detection data signals. Among them, in order to reduce the dead volume and enhance the detection performance, it is conducive to better gas detection. As shown in FIG. 5 , the structure of the bulk acoustic wave resonator array 109 is as follows, which includes:

The support plate 503 has a glass micro-channel 505 on the front of the support plate 503, and the air inlet and the air outlet are respectively arranged at the left and right ends of the glass micro-channel 505; the air inlet and the air outlet are respectively connected with quartz capillaries 502, It is used for gas connection; among them, the glass microfluidic channel is processed by laser to ensure the accuracy of its size. In fact, the micro-chromatographic column and the detector can also be directly fabricated on the same substrate by micro-fabrication, but this method is expensive and difficult to manufacture. runner and bonding.

A bulk acoustic wave resonator array 504 is arranged on the support plate 3, and 501 is a mixed gas sample.

A bulk acoustic wave resonator array 504 is provided on the support plate 503 under the glass microchannel, wherein different bulk acoustic wave resonators are decorated with polymers with the function of adsorbing different types of gas to be tested, so as to facilitate the realization of Detection of mixed gases that cannot be separated by the separation column. Moreover, the detection effect is best when the frequency of the bulk acoustic wave resonator device is set to 2.44 GHz.

Among them, in order to detect the modification of the bulk acoustic wave resonator, a characterization device can also be provided, including: a Fourier transform infrared spectrometer to characterize whether the polymer is successfully modified on the surface of the bulk acoustic wave resonator; and atomic force Microscopy for characterization of the morphology and film thickness of bulk acoustic wave resonator surface-modified polymer films.

Among them, the detection principle of the BAW resonator device is as follows: as shown in Figure 4, when the gas to be tested after chromatographic separation of the chromatographic column reaches the surface of the resonator sensing area of the BAW resonator device through the gas path, the resonant frequency of the device will be caused. There is a certain degree of decline, and the degree of decline is positively correlated with the gas concentration (quantitative identification), and the gas is qualitatively identified according to the different time of gas flow, so as to realize further detection of organic volatile gases.

In order to better illustrate the technical solution of the present application, the working principle of the gas detection system of the present application is now described as follows:

First, inject the sample to be tested (in order to achieve higher efficiency of gas separation and detection, 5 microliters of the liquid to be tested at room temperature are mixed in turn as the sample to be tested) for sample injection. Specifically, headspace micro-injection is used. The sample needle drives the sample to be tested into the sample inlet 104 at a constant speed, and the sample to be tested is connected between the carrier gas subsystem and the gas path of the micro chromatographic column 7 under the drive of the sample injection pump 105 . Driven by the carrier gas output from the carrier gas subsystem, the sample is sent to the micro-chromatographic column 107 for gas separation. This period of time is 2 minutes.

The gas to be tested output by the micro chromatographic column 107 is continuously loaded into the BAW resonator device array 109 by the carrier gas, the resonant frequency change of the BAW resonator array 109 is detected, and the data is analyzed and displayed by the network analyzer 110 .

Among them, when it is difficult to chromatographically separate some mixed gases through a chromatographic column (the obtained peak positions overlap), the present invention can also realize further detection. The specific instructions are as follows:

In the present invention, different polymers are modified on different bulk acoustic wave resonators in the bulk acoustic wave resonator array, so as to realize the identification of different gases in the unseparated mixed gas after passing through the micro chromatographic column. Specifically, for example, in order to qualitatively and quantitatively identify gases 1 and 2 with different mixing ratios, which are difficult to be separated by a chromatographic column, the bulk acoustic wave resonators in the array are respectively decorated with polymer A and polymer B, wherein the polymer The BAW resonator modified by A has a greater response to gas 1, and the BAW resonator modified by polymer B has a greater response to gas 2. Based on this orthogonality, the distinction of mixed gases can be achieved.

To sum up, the manufacturing method of the micro-chromatographic separation column provided by this application, the chromatographic separation column is manufactured into a square spiral structure, this structure can maximize the separation efficiency of the chromatographic column, and the glass plate ( Can be a Pyrex glass plate) sealed to the bottom plate. The above-mentioned manufacturing method of the present application is the first method for manufacturing a chromatographic separation column, which is beneficial to the manufacture of a tiny chromatographic separation column, so as to facilitate the miniaturization of a gas detection and analysis device. The analysis system provided by the present application can conveniently realize the separation and detection of the mixed gas. The whole system has the characteristics of miniaturization, simplicity, high identification efficiency and compatibility with semiconductor technology. And the bulk acoustic wave resonator device of the present application can also be set as an array-type bulk acoustic wave resonator, and different bulk acoustic wave resonators are decorated with polymers with the function of adsorbing different types of gas to be tested, so that the traditional BAW resonator can be realized. Qualitative and quantitative identification detection of binary gas mixtures with overlapping peak positions that cannot be identified by a single gas chromatographic column.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the scope of the present invention. within the scope of protection.

Claims (10)

1. a preparation method of a miniature chromatographic separation column, is characterized in that, comprises: A. Use silicon material to make micro-chromatographic column base; B. Making a micro-channel with a square helical structure at the bottom of a glass plate; C. Bond the bottom of the glass plate with the micro-flow channel with the square helical structure and the upper surface of the substrate to form a micro-chromatographic separation column. 2. The method according to claim 1, wherein the step B comprises: B1. Through photolithography and deep silicon etching process, a micro-channel with a square spiral structure is manufactured; B2. Modification of the stationary phase is performed on the inner surface of the microfluidic channel. 3. The method according to claim 2, wherein the step B2 comprises: B21. Activating the inner surface of the microchannel by octamethylcyclotetrasiloxane; B22. 100% polydimethylsiloxane is modified on the inner surface of the microfluidic channel by dynamic coating; B23. Crosslinking the stationary phase to ensure the stability of the stationary phase; B24, heating and aging for 4 hours. 4. a micro-chromatographic separation column made based on the preparation method of claim 1, is characterized in that, comprising: base, A glass plate, the bottom of which is etched with a micro-flow channel of a square helical structure; Wherein, the bottom of the glass plate is bonded with the upper surface of the substrate. 5. A micro gas analysis system, based on the micro chromatographic separation column of claim 4, is characterized in that, comprising: A sample injection system, comprising: a sample injection port and a sample injection pump; wherein, the sample injection pump is communicated with the sample injection port through a gas pipeline to provide power support for sample injection; a carrier gas subsystem, including a pressure control valve, a pressure gauge and a flow meter, for precise control of the gas flow, and connected with the outlet of the inlet sub-system for loading the sample into the micro-chromatographic separation column; Wherein, the micro-chromatographic separation column is connected with the inlet sub-system and the carrier gas subsystem, and is used to separate the sample; The bulk acoustic wave resonator array is connected to the outlet of the micro chromatographic column, and is used for identifying and detecting the gas. 6. The system of claim 5, wherein the BAW resonator array comprises: a support plate, on which a bulk acoustic wave resonator array region is arranged; A glass micro-flow channel is arranged on the bulk acoustic wave resonator array area; wherein, the two ends of the glass micro-flow channel are respectively provided with an air inlet and an air outlet; wherein, the air inlet and the air outlet are Quartz capillaries are respectively connected to the upper parts for gas connection; Wherein, the air inlet is connected to the outlet of the micro chromatographic column through the quartz capillary; the air outlet is connected to a waste gas recovery device through the quartz capillary. 7 . The system according to claim 5 , wherein, in the BAW resonator array, different BAW resonators are decorated with different polymers, which have the effect of adsorbing different types of gas to be tested. 8 . 8. The system of claim 5, wherein the carrier gas subsystem comprises: The nitrogen cylinder 1, the pressure control valve, the pressure gauge 2 and the flow meter 3 are connected with the carrier gas in sequence. 9. The system of claim 5, further comprising: Connected to the BAW resonator array is a network analyzer for sweeping measurements over a wide frequency band to determine network parameters and display signals. 10. The system of claim 5, further comprising: Temperature control and digital display for temperature control of the environment in which the micro-column is located.