CN102095746A - Micro solenoid radio frequency coil for microfluid nuclear magnetic resonance detection and manufacturing method thereof - Google Patents

Abstract

The invention relates to a micro-solenoid radio frequency coil for microfluid nuclear magnetic resonance detection and a manufacturing method thereof, comprising a bottom inclined strip coil on an insulating substrate, two left and right rows of bottom coils, and a column arranged on the top of the bottom coil shaped coil, the microfluidic channel between the left and right rows of bottom coils, and the top layer of oblique strip coil located above the microfluidic channel; The two ends of the shaped coil are respectively connected to the cylindrical coil arranged on the top of the bottom coil in dislocation, and the oblique strip coil at the bottom layer and the oblique strip coil at the top layer have opposite inclination directions. The invention adopts photoresist lithography technology and copper electroplating coil technology to manufacture. The invention overcomes the shortcomings of micron-scale solenoid radio frequency coils that are not easily wound, and has the advantages of high radio frequency magnetic field uniformity, etc., and can be used for nuclear magnetic resonance detection of rare and expensive samples.

Description

Micro-solenoid radio-frequency coil for microfluidic nuclear magnetic resonance detection and manufacturing method thereof

technical field

The invention relates to a radio frequency coil used for microfluid nuclear magnetic resonance detection, in particular to a radio frequency micro coil with a uniform magnetic field distribution of a solenoid and a manufacturing method thereof. the

Background technique

NMR spectroscopy is non-destructive to samples and is therefore widely used in the fields of chemistry, biomedicine and materials science. The nuclear magnetic resonance radio frequency coil can use a separate transceiver or a coil with both transceivers. The transmitting function is used to transmit the pulse sequence to excite the magnetization vector of the measured sample, and the receiving function is used to receive the free induction attenuation generated by the excited spin. Signal. The Fourier transform of the signal can be used to obtain the nuclear magnetic resonance spectrum, and the information such as the composition of the measured sample can be obtained. According to different application fields, general RF coils include solenoid coils, planar coils, saddle coils, birdcage coils, butterfly coils, and phase array coils. (Hoult, D.I. and R.E. Richards, SIGNAL-TO-NOISE RATIO OF NUCLEAR MAGNETIC-RESONANCE EXPERIMENT. Journal of Magnetic Resonance, 1976.24(1): p.71-85.) Discussed in the literature compared to other types of coils, solenoid It has the advantages of high sensitivity and uniform magnetic field distribution, so the current conventional commercial NMR spectroscopy detection technology uses a probe with an aperture of 5mm, that is, a solenoid coil is formed by winding a wire on a capillary glass tube. Its sample detection limit is about 5×109mol, which is far worse than other detection techniques such as infrared spectroscopy and mass spectrometry. (Peck, T.L., R.L.Magin, and P.C. Lauterbur, DESIGN AND ANALYSIS OF MICROCOILS FOR NMRMICROCOILS FOR NMRMICROSCOPY. Journal of Magnetic Resonance Series B, 1995.108(2): p.114-124.) Theoretical and experimental verification in the literature when the coil diameter is about 100um , the signal-to-noise ratio (S/N) of the sample per unit volume is inversely proportional to the coil diameter; when it is less than 100um, it is inversely proportional to the square root of the coil diameter, so many documents use microcoils to improve sensitivity. However, the winding method is not easy to realize at the micro scale, so it is not easy to manufacture micro solenoid coils. (Massin, C., et al., Planar microcoil-based microfluidic NMR probes. Journal of Magnetic Resonance, 2003.164(2): p.242-255.) The literature has attracted the attention of many scholars. The resonance probe detects tiny sample solutions in the microfluidic channel. It is the literature (Peck, T.L., et al., NMRMICROSPECTROSCOPY USING 100-MU-M PLANAR RF-COILS FABRICATEDON GALLIUM-ARSENIDE SUBSTRATES.Ieee Transactions on Biomedical Engineering, 1994.41(7 ): p.706-709.). Although the planar microcoil has low sensitivity and poor uniformity of the radio frequency magnetic field, it can be mass-produced automatically by modern micro-manufacturing lithography technology under the size of a micron; in addition, the planar microcoil is easy to combine with a chip-based microfluidic system, so that for manipulating microfluidics and increasing integration performance. Ehrmann, K., who is in the same research group as Massin, C., proposed the use of MEMS technology to make solenoidal coils and Helmholtz coils in 2006-2007, and applied them to the detection of nuclear magnetic resonance spectra of mammalian cells. the

Domestic research scholars such as Wang Ming, Li Xiaonan, etc. in the Chinese patent application numbers 200610164809.3, 200710179309.1, 200910081526.6, etc., as well as the literature "Design of high signal-to-noise ratio planar microcoils for nuclear magnetic resonance micro-detection of nanoscale biochemical samples.", "MEMS-based Design and manufacture of nuclear magnetic resonance miniature planar helical radio frequency coils in High Q NMR planar microcoils. Chinese patent 200910091597.4 "A Nuclear Magnetic Resonance Radio Frequency Microcoil and Its Manufacturing Method" relates to Helmholtz type (saddle) nuclear magnetic resonance radio frequency microcoils, but produces the same size radio frequency magnetic field, Helmholtz type (saddle) Shape) The resistance of the NMR radio frequency micro-coil is larger than that of the micro-solenoid radio frequency coil, so the signal-to-noise ratio will be relatively small. the

Contents of the invention

What the present invention aims to solve is that the existing conventional microfluidic detection is not easy to be suitable for the detection of micro samples; the radio frequency magnetic field of the miniature planar helical coil is uneven and the sensitivity is low; the miniature solenoid coil is not easy to be manufactured by the conventional winding method; The magnetic field, Helmholtz type (saddle) coil has a large resistance, which reduces the signal-to-noise ratio and other issues. the

In order to solve the above-mentioned technical problems, the present invention provides a micro-solenoid radio frequency coil for nuclear magnetic resonance microfluid detection. The cylindrical coil on the top of the bottom coil, the microfluidic channel between the left and right rows of bottom coils, and the top layer of diagonal strip coils above the microfluidic channel; the two ends of the bottom diagonal strip coil are respectively misaligned with the left and right rows of bottom coils connection, the two ends of the top-layer oblique strip-shaped coil are respectively dislocated and connected to the column-shaped coil arranged on the top of the bottom coil, and the inclination directions of the bottom-layer oblique strip-shaped coil and the top-layer oblique strip-shaped coil are opposite. the

In order to improve the signal-to-noise ratio of the present invention, the above-mentioned bottom slant strip coil, bottom coil, columnar coil and top layer slant strip coil are all made of low-impedance metal materials, because copper not only has high conductivity, but also is cheap and durable Excellent corrosion resistance, easy to combine with integrated circuits, so the coil material is preferably copper. the

The above-mentioned microfluidic channel adopts a capillary glass tube, and its cross-sectional shape is preferably square, which is used to place the measured sample. the

Because the mechanical properties of traditional silicon substrates are relatively brittle and expensive, the insulating substrate of the present invention is made of heat-resistant glass or other insulating and heat-resistant polymer materials, and the insulating substrate made of the aforementioned materials has biological properties. Compatibility, low cost, and the substrate capacitance (substrate capacitance) generated between the coils is small, and has little influence on the conduction current in the coil, thereby reducing power loss. the

The number of bottom coils and cylindrical coils in each row is the same, n, and the number of bottom slant strip coils and top slant strip coils is the same, n-1, n is a natural number greater than 1. the

The manufacturing method of the present invention is mainly based on photoresist lithography technology and copper electroplating coil technology, specifically includes the following steps:

1. Deposit a layer of photoresist on the insulating substrate;

2. UV photolithography is performed on the deposited photoresist to form two rows of grooves on the left and right, and then fill the grooves with low-impedance metal materials by electroplating to form two rows of bottom coils on the left and right;

3. Photoetching the photoresist in the middle of the left and right rows of bottom coils to form oblique strip-shaped grooves, and then filling the grooves with low-impedance metal materials by electroplating to form the bottom oblique strip-shaped coils;

4. Deposit another layer of photoresist on the plated bottom coil and the unphotoresisted photoresist on both sides of the bottom coil;

5. The photoresist precipitated in step 4 is irradiated with ultraviolet lithography to form a cylindrical groove, and then filled with a low-impedance metal material into the groove by electroplating to form two rows of cylindrical coils;

6. The photoresist between the two rows of column coils is irradiated by ultraviolet lithography to form oblique strip-shaped grooves, and then filled with low-impedance metal materials into the grooves by electroplating to form the top layer of oblique strip-shaped coils;

7. From one side, irradiate the photoresist located on the oblique strip coil at the bottom layer and the oblique strip coil at the top layer by ultraviolet lithography to form a through hole whose center line is perpendicular to the cylindrical coil, and then place the microfluidic channel in the aforementioned through hole. In the hole, the finished product is made. the

The present invention can also adopt the following steps to manufacture:

1. Deposit a layer of photoresist on the insulating substrate;

2. UV photolithography is performed on the deposited photoresist to form two rows of grooves on the left and right, and then fill the grooves with low-impedance metal materials by electroplating to form two rows of bottom coils on the left and right;

3. Perform photolithography on the photoresist in the middle of the left and right rows of bottom coils to form six oblique strip grooves, and then fill the grooves with low-impedance metal materials by electroplating to form the bottom oblique strip coils;

4. Deposit another layer of photoresist on the plated bottom coil and the unphotoresisted photoresist on both sides of the bottom coil;

5. The photoresist precipitated in step 4 is irradiated with ultraviolet lithography to form a cylindrical groove, and then filled with a low-impedance metal material into the groove by electroplating to form two rows of cylindrical coils;

6. Place the microfluidic channel between two rows of cylindrical coils, then deposit photoresist on the microfluidic channel until its top is parallel to the top of the columnar coil, and then irradiate the photoresist with ultraviolet lithography to form oblique stripes Shaped grooves, and then fill the grooves with low-impedance metal materials by electroplating to form top-layer oblique strip coils, and the finished product is obtained. the

When using this method, the microfluidic channel should be made of heat-resistant capillary glass. the

Compared with other types of photoresists, SU-8 photoresist can manufacture high aspect ratio MEMS microstructures (refer to coils in the present invention); have good mechanical properties and thermal stability; non-conductive, when electroplating Can be directly insulated. Therefore, the photoresist used in the two methods is preferably SU-8 photoresist

The invention can be used in modern micro-manufacturing photolithography and electroplating technology for automatic batch production, can generate a uniform radio frequency magnetic field, and its coil cross-sectional size is on the order of tens to hundreds of microns, which is especially suitable for the detection of rare and expensive samples. the

Description of drawings

The present invention will be described in detail below in conjunction with the accompanying drawings and specific examples, but not as a limitation of the present invention. the

Fig. 1 is a structural schematic diagram of the present invention. the

Fig. 2a is a schematic diagram of step 1 of the production method of the present invention. the

Fig. 2b and Fig. 2c are schematic diagrams of Step 2 of the production method of the present invention. the

Fig. 2d is a schematic diagram of step 3 of the production method of the present invention. the

Fig. 2e is a schematic diagram of step 4 of the production method of the present invention. the

Fig. 2f and Fig. 2g are schematic diagrams of step 5 of the production method of the present invention. the

Figure 2h and Figure 2i are schematic diagrams of steps 6 and 7 of the manufacturing method of the present invention. the

Detailed ways

Referring to Fig. 1, the insulating substrate (1) of the present embodiment is a rectangular sheet made of heat-resistant glass, and the microfluidic channel (4) for placing the sample to be tested is a square capillary glass tube, and the left and right rows of bottom coils ( 7) There are 7 coils in each row, and the columnar coils (3) arranged on the top of the bottom coils (7) are also 7 in each row, connecting the bottom oblique strip coils (2) and There are 6 top oblique strip coils (5) connecting the two rows of cylindrical coils (3), and the inclination directions of the bottom oblique strip coils (2) and the top oblique strip coils (5) are opposite. The above-mentioned coils are made of copper, and are connected to each other to form a solenoid coil with six turns. the

Referring to Fig. 2a--2i, the manufacturing method of the present embodiment is as follows:

1. Deposit SU-8 photoresist (6) with a thickness of 20 microns on the insulating substrate (1) (see Figure 42a);

2. UV photolithography is performed on the deposited photoresist to form a total of seven pairs of left and right grooves (see Figure 2b). Side bottom coil (7), totally seven pairs (seeing among Fig. 2c);

3. Perform photoetching on the photoresist between the left and right rows of bottom coils (7) to form six oblique grooves, and then fill the grooves with low-impedance metal materials by electroplating to form six 20-micron-high Bottom oblique strip coil (2) (see Figure 2d);

4. Precipitate a layer of 80 micron thick SU-8 photoresist on the plated bottom coil (7), oblique strip coil (2) and the unphotoresisted photoresist on both sides of the bottom coil (7) (See Figure 2e);

5. Perform ultraviolet lithography on the photoresist deposited in step 4 to form a columnar groove with a depth of 80 microns (see Figure 2f), and then fill the groove with a low-impedance metal material by electroplating to form two rows of 80 microns High cylindrical coils (3), a total of seven pairs (see Figure 2g);

6. Ultraviolet photolithography is performed on the SU-8 photoresist between the two rows of column coils (3) to form six oblique strip grooves (see Figure 2h), and then fill the grooves with low voltage by electroplating. Impedance metal material forms six top layer oblique strip coils (5) (see Fig. 2i);

Seven pairs of left and right bottom coils in step (2), six oblique strip coils in step (3), seven pairs of columnar coils on the left and right in step (5), and six top oblique strip coils in step (6), Wrap around to form a six-turn solenoid coil;

7. Referring to Figure 2i, from the front (or back) direction, the photoresist surrounded by the six-turn solenoid is located at the bottom oblique strip coil (2) and the top layer oblique strip coil (5) for ultraviolet light Engraved irradiation to form a square hole whose center line is perpendicular to the cylindrical coil (3), and then put a square capillary glass tube into the square through hole to form a microfluidic channel (4), and the finished product is obtained. the

The working principle of the present invention is:

Put the tested sample in the microfluidic channel (4) in the main magnetic field, the tested sample will be magnetically polarized, and the magnetization vector will appear macroscopically; then apply current to the micro-solenoid radio frequency coil to generate a magnetic field perpendicular to the main magnetic field And the radio frequency magnetic field with good uniformity, the uniform radio frequency magnetic field makes the atomic nuclei in the tested sample produce a consistent flip angle, that is, the atomic nuclei in the tested sample perform synchronous precession, and the synchronous precession makes the tested sample show macroscopically The transverse magnetization vector, the transverse magnetization vector generates an induced electromotive force in the micro-solenoid radio frequency coil, and after a period of recording, the free induction attenuation signal is obtained, and then the free induction attenuation signal is Fourier transformed to obtain the nuclear magnetic resonance spectrum. the

Claims (8)

1. A micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection, characterized in that it includes a bottom oblique strip coil (2) on an insulating substrate (1), two left and right rows of bottom coils (7), The cylindrical coil (3) arranged on the top of the bottom coil (7), the microfluidic channel (4) located between the left and right rows of bottom coils (7), and the top layer of oblique strip coil located above the microfluidic channel (4) (5); the two ends of the bottom layer of oblique strip coil (2) are respectively connected to the left and right two rows of bottom coils (7) in dislocation, and the two ends of the top layer of oblique strip coil (5) are respectively connected to the bottom coil (7) on the top The cylindrical coils (3) are dislocated and connected, and the oblique strip coils (2) on the bottom layer and the oblique strip coils (5) on the top layer have opposite inclination directions. 2. The micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection according to claim 1, characterized in that the bottom oblique strip coil (2), the bottom coil (7), the cylindrical coil (3 ) and the top-layer oblique strip coil (5) are made of low-impedance metal materials. 3. The micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection according to claim 1, characterized in that the microfluidic channel (4) is a capillary glass tube. 4. The micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection according to claim 1, characterized in that the insulating substrate (1) is made of heat-resistant glass or other insulating and heat-resistant polymer materials constitute. 5. The micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection according to any one of claims 1 to 4, characterized in that the number of bottom coils (7) and cylindrical coils (3) in each row is the same, The number is n, the number of the bottom oblique strip coils (2) and the top layer oblique strip coils (5) is the same, n-1, and the aforementioned n is a natural number greater than 1. 6. The micro-solenoid radio frequency coil for microfluidic nuclear magnetic resonance detection as claimed in claim 5, characterized in that the number of bottom coils (7) and cylindrical coils (3) in each row is 7, and the bottom layer is inclined There are 6 strip coils (2) and top-layer oblique strip coils (5), which jointly form a solenoid coil with six turns. 7. the manufacture method of the micro-solenoid radio-frequency coil that is used for microfluid nuclear magnetic resonance detection described in any one of claims 1 to 6, it is characterized in that comprising the steps: (1) Precipitating a layer of photoresist (6) on the insulating substrate (1); (2) Ultraviolet photolithography is performed on the deposited photoresist to form two rows of grooves on the left and right, and then the grooves are filled with low-impedance metal materials by electroplating to form two rows of bottom coils on the left and right (7); (3) Photoetching the photoresist between the left and right rows of bottom coils (7) to form six oblique strip grooves, and then filling the grooves with low-impedance metal materials by electroplating to form the bottom oblique strip coils (2); (4) Precipitating a layer of photoresist on the plated bottom coil (7) and the unphotoresisted photoresist on both sides of the bottom coil (7); (5) UV photolithography is performed on the photoresist deposited in step (4) to form a cylindrical groove, and then a low-impedance metal material is filled into the groove by electroplating to form two rows of cylindrical coils (3); (6) UV photolithography is performed on the photoresist between the two rows of column coils (3) to form oblique strip-shaped grooves, and then the grooves are filled with low-impedance metal materials by electroplating to form oblique strip-shaped top layers Coil(5); (7) UV photolithography is performed on the photoresist located on the bottom oblique strip coil (2) and the top oblique strip coil (5) from one side to form a through hole whose center line is perpendicular to the cylindrical coil (3) , and then place the microfluidic channel (4) in the aforementioned through hole to obtain the finished product. 8. the manufacture method of the micro-solenoid radio-frequency coil that is used for microfluid nuclear magnetic resonance detection described in any one of claims 1 to 6, it is characterized in that comprising the steps: (1) Precipitating a layer of photoresist (6) on the insulating substrate (1); (2) Ultraviolet photolithography is performed on the deposited photoresist to form two rows of grooves on the left and right, and then the grooves are filled with low-impedance metal materials by electroplating to form two rows of bottom coils on the left and right (7); (3) Perform photolithography on the photoresist between the left and right rows of bottom coils (7) to form oblique strip-shaped grooves, and then fill the grooves with low-impedance metal materials by electroplating to form the bottom oblique strip-shaped coils (2 ); (4) Precipitating a layer of photoresist on the plated bottom coil (7) and the unphotoresisted photoresist on both sides of the bottom coil (7); (5) UV photolithography is performed on the photoresist deposited in step (4) to form a cylindrical groove, and then a low-impedance metal material is filled into the groove by electroplating to form two rows of cylindrical coils (3); (6) Place the microfluidic channel (4) between two rows of cylindrical coils (3), and then deposit photoresist on the microfluidic channel (4) until its top is parallel to the top of the columnar coils (3), Then irradiate the photoresist with ultraviolet lithography to form oblique strip-shaped grooves, and then fill the grooves with low-impedance metal materials by electroplating to form top-layer oblique strip-shaped coils (5), and the finished product is obtained.

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