CN101782539B - Microfluidic biomone detection chip based on nuclear magnetic resonance - Google Patents
Microfluidic biomone detection chip based on nuclear magnetic resonance Download PDFInfo
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- CN101782539B CN101782539B CN2010190261138A CN201019026113A CN101782539B CN 101782539 B CN101782539 B CN 101782539B CN 2010190261138 A CN2010190261138 A CN 2010190261138A CN 201019026113 A CN201019026113 A CN 201019026113A CN 101782539 B CN101782539 B CN 101782539B
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Abstract
The invention discloses a microfluidic biomone detection chip based on nuclear magnetic resonance, comprising a main magnetic field generating device, an RF magnetic field generator, a signal receiver, a microfluidic path device and a facing bar, wherein the main magnetic field generating device generates a horizontal even main magnetic field, the RF magnetic field generator generates a vertical RF magnetic field, and the signal receiver receives the nuclear magnetic resonance signal of microfluidic biomone; the RF magnetic field generator comprises a first matrix substrate and a surface plate RF transmitting coil etched on the matrix substrate; the receiver comprises a second substrate, a third substrate and surface plate RF receiving coils etched on the two substrates, wherein the second substrate and the third substrate are symmetrically distributed on two the sides of the microfluidic path device which comprises a microfluidic path. The detection chip of the invention has small volume as well as low manufacturing and maintenance cost, is suitable for the routine determination and analysis of microfluidic biomone and is especially suitable for the family instant medical detection of human body fluid ingredient and content.
Description
Technical field
The present invention relates to a kind of magnetic resonance detection chip, be specifically related to that a kind of volume is small, manufacturing and the cheap micro-fluidic biological detection of particles chip of maintenance cost based on nuclear magnetic resonance technique.
Background technology
At present, optical detecting method is widely used in the detection of biomone in the microfluid passage, but this method itself has certain limitation.For example, laser-Induced Fluorescence Detection only be applicable to have the natural fluorescence characteristic or can with the interactional molecule particle of fluorescent powder, do not satisfy this requirement and most of biomolecule and compound are strict.Simultaneously, optical detecting method has the visual demand of sense channel to area-of-interest and has also limited the pick-up unit material chosen in testing process.In addition, most of optical detecting method only is confined to the analysis to known compound.
Nuclear magnetic resonance technique can be good at overcoming above problem because its unique non-destructive has online detection and the function of physical form with function assessment information is provided simultaneously.But traditional nuclear magnetic resonance technique adopts bigger radio-frequency coil to surround whole measuring samples, is applied to have when biomone detects in the microfluid that sensitivity is relatively poor, signal to noise ratio (S/N ratio) and the lower shortcoming of resolution.Based on nuclear magnetic resonance technique, the miniature solenoid coil that is wound in microfluid passage can improve sensitivity and the resolution that biomone detects in the microfluid greatly, but the manufacture process of miniature solenoid coil is relatively more difficult, is difficult to be applicable to production in enormous quantities.Simultaneously, present most of high resolution NMR detection technique all is in cryogenic magnet, to carry out, and the application of superconducting magnet inevitably can increase the manufacturing and the maintenance cost of pick-up unit; Current some other nuclear magnetic resonance technique that is applied to the microfluid high resolution detection of studying, C.L.Degen for example, M.Poggio; H.J.Mamin; Et al.Nanoscale magnetic resonance imaging, PNAS 2009,106 (5): 1313-1317; Though do not need superconducting magnet, still need the testing environment of ultralow temperature.These devices or volume are very huge, or manufacturing technology is comparatively complicated, are difficult to be applicable to that the instant medical science of the conventional sense, particularly " family oriented " of biomone in the microfluid detects.
Summary of the invention
Goal of the invention: in order to overcome the deficiency that exists in the prior art; The present invention provides that a kind of volume is small, manufacturing and the cheap micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique of maintenance cost; This detection chip is applicable to the conventional sense and the analysis of biomone in the microfluid, and the instant medical science that is specially adapted to " family oriented " human body fluid composition and content detects.
Technical scheme: to achieve these goals; A kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique of the present invention comprises main field generation device, the RF magnetic field generator that produces the RF magnetic field of vertical direction that produces the even main field of horizontal direction, signal receiver, microfluid passage device and the back up pad that receives biomone NMR signal in the microfluid; Said RF magnetic field generator comprises first host substrate and is etched in the dull and stereotyped radio-frequency sending coil on the host substrate; Said receiver comprises second substrate, the 3rd substrate and is etched in the dull and stereotyped RF receiving coil group on these two substrates that second substrate and the 3rd substrate are symmetrically distributed in microfluid passage device both sides; Said microfluid passage device comprises microfluid passage.
Said main field generation device comprises two parallel permanent magnets and is connected the iron yoke that these two permanent magnets constitute magnetic circuit; Also can realize by the permanent magnet magnetic circuit that other structure is formed; Said RF magnetic field generator is positioned at the top of permanent magnet.
The xsect of said passage is oval or trapezoidal.
Said microfluid passage is single or a plurality of, when adopting a plurality of microfluid passage, can carry out partition test to the particle of different sizes; The cross-sectional area of each microfluid passage can be unequal; Its cross-sectional geometry can be oval, trapezoidal or other geometric configuration; The caliber of each microfluid passage is heterogeneous; Promptly the cross-sectional area along each position of flow velocity direction can not equate entirely; Wherein the microfluid passage sectional area with corresponding position, RF receiving coil group position is bigger, and under the situation of constant flow, this position flow rate of fluid that can reduce to flow through is to guarantee the complete collection NMR signal of RF receiving coil.
The group number of said dull and stereotyped RF receiving coil group is M * N (M; N >=1); Every group of dull and stereotyped RF receiving coil group comprises two dull and stereotyped RF receiving coils; Per two dull and stereotyped RF receiving coils are symmetrically distributed in the both sides of microfluid passage, and the value of N equals the number of microfluid passage, and the value of M is the group number of the corresponding RF receiving coil of each microfluid passage.
Per two dull and stereotyped RF receiving coils are symmetrically distributed in two of microfluid passage and survey the microfluid of flowing through is detected simultaneously, merge sensitivity and signal to noise ratio (S/N ratio) that signal that two RF receiving coils respond to can increase signal receiver; Each microfluid passage correspondence is organized (M >=1) RF receiving coil more; When microfluid was flowed through a certain group of RF receiving coil, the pulse train that can apply different types to the radio-frequency sending coil in the signal projector was to satisfy the needs that RF receiving coil detects to the specified type particle.
Said back up pad is the rectangle thin plate, perhaps the thin plate of other geometric configuration; Said dull and stereotyped radio-frequency sending coil is a plane thread shape structure, and its material can be selected copper, also can select other Low ESR metal material.
Optimum position in the described main field is the best position of uniformity of magnetic field effect between two permanent magnets.
Beneficial effect: a kind of micro-fluidic biological detection of particles chip of the present invention based on nuclear magnetic resonance technique; Volume is small; Manufacturing and maintenance cost are cheap; Be applicable to the conventional sense and the analysis of biomone in the microfluid, the instant medical science that is specially adapted to " family oriented " human body fluid composition and content detects.
Description of drawings
Fig. 1 is the vertical view of a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique of the present invention;
Fig. 2 is A-A master's cut-open view among Fig. 1;
Fig. 3 is a B-B cut-open view among Fig. 2;
Fig. 4 is a C-C cut-open view among Fig. 2.
Embodiment
Below in conjunction with accompanying drawing the present invention is done explanation further.
Shown in Fig. 1-4, a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique of the present invention comprises producing the even main field B of horizontal direction
0The main field generation device, produce the RF magnetic field B of vertical direction
1The RF magnetic field generator, receive signal receiver, microfluid passage device 105 and the back up pad 110 of biomone NMR signal in the microfluid; The RF magnetic field generator comprises first host substrate 104 and is etched in the dull and stereotyped radio-frequency sending coil 103 on first host substrate 104; Signal receiver comprises second substrate 106, the 3rd substrate 107 and is etched in the dull and stereotyped RF receiving coil group on these two substrates; Six groups of dull and stereotyped RF receiving coil groups (121,122,123 and 131,132,133) are arranged in the present embodiment, and second substrate 106 and the 3rd substrate 107 are symmetrically distributed in microfluid passage device 105 both sides; Microfluid passage device 105 comprises first microfluid passage 108 and second microfluid passage 109, can increase the quantity of microfluid passage according to the detection needs.
As shown in Figure 2, the main field generation device comprises that the permanent magnet 101 of two parallel rectangular structure is connected the iron yoke 102 that these two permanent magnets 101 constitute the rectangular structure of magnetic circuit with one; The material of permanent magnet 101 is a neodymium iron boron, also can select other rare earth iron permanent-magnet material, and the material of iron yoke 102 is an electrical pure iron, also can select other to have the metal material of high magnetic permeability; The RF magnetic field generator is positioned at the top of permanent magnet 101.Every group of RF receiving coil group comprises two RF receiving coils, and second substrate 106 and the 3rd substrate 107 and the etching RF receiving coil on it is symmetrically distributed in microfluid passage device 105 both sides, is used for the reception of microfluid NMR signal jointly.Microfluid passage device 105 comprises single or a plurality of microfluid passage, when adopting a plurality of microfluid passage, can carry out partition test to the particle of different sizes; Microfluid passage device 105 comprises first microfluid passage 108 and second microfluid passage 109 in the present embodiment; And adopt second substrate 106 and the 3rd substrate 107 to its sealing; The cross-sectional area of two microfluid passage does not wait, and is respectively applied for the microfluid that transportation contains different sized particles scopes.The optimum position that back up pad 110 is used for regulating and support microfluid passage device and signal receiver and makes it to be positioned at main field, the optimum position in the main field are the best position of uniformity of magnetic field effect between two permanent magnets; Back up pad 110 is a rectangle thin plate, and material can be selected glass or other nonmetallic materials for use.
As shown in Figure 1, first host substrate 104 is a rectangle thin plate, and its material can be selected glass for use, also can select other polymeric material, and radio-frequency sending coil 103 is a plane thread shape structure, and its material can be selected copper or other Low ESR metal material for use.
As shown in Figure 3, second host substrate 106 is a rectangle thin plate, and its material can be selected glass for use; Also can select other polymeric materials; The RF receiving coil group is one 3 * 2 a matrix, wherein has six RF receiving coils (121,122,123 and 131,132,133) etching on first host substrate 106, and each RF receiving coil all is plane thread shape structure; The material of coil can be selected copper or other Low ESR metal material for use; RF receiving coil 121,122 has identical size with 123, and 131,132 and 133 have identical size, and 121 and 131 size then can not wait.
As shown in Figure 4, the cross-sectional area of each microfluid passage can be unequal, and its cross-sectional geometry can be oval, trapezoidal or other geometric configuration.First microfluid passage 108 in the present embodiment and the caliber of second microfluid passage 109 are not equally distributed, promptly along each self-flow rate direction (v
1And v
2) everywhere cross-sectional area can be unequal; Wherein the caliber with the microfluid passage of 140 corresponding positions, RF receiving coil position is bigger; Under the situation of constant flow, this position flow rate of fluid that can reduce to flow through is to guarantee the complete collection NMR signal of RF receiving coil.
The above only is a preferred implementation of the present invention; Be noted that for those skilled in the art; Under the prerequisite that does not break away from the principle of the invention, can also make some improvement and retouching, these improvement and retouching also should be regarded as protection scope of the present invention.
Claims (6)
1. the micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique is characterized in that: comprise main field generation device, the RF magnetic field generator that produces the RF magnetic field of vertical direction that produces the even main field of horizontal direction, signal receiver, microfluid passage device (105) and the back up pad (110) that receives biomone NMR signal in the microfluid; Said RF magnetic field generator comprises first host substrate (104) and is etched in the dull and stereotyped radio-frequency sending coil (103) on first host substrate (104); Said receiver comprises second substrate (106), the 3rd substrate (107) and is etched in the dull and stereotyped RF receiving coil group on these two substrates that second substrate (106) and the 3rd substrate (107) are symmetrically distributed in microfluid passage device (105) both sides; Said microfluid passage device (105) comprises microfluid passage (108).
2. a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique according to claim 1 is characterized in that: said main field generation device comprises two parallel permanent magnets (101) and is connected the iron yoke (102) that these two permanent magnets (101) constitute magnetic circuit; Said RF magnetic field generator is positioned at the top of permanent magnet (101).
3. a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique according to claim 1 is characterized in that: the xsect of said passage (108) is for oval or trapezoidal.
4. according to claim 1 or 3 described a kind of micro-fluidic biological detection of particles chips based on nuclear magnetic resonance technique; It is characterized in that: the group number of said dull and stereotyped RF receiving coil group is M * N, M, N >=1; Every group of dull and stereotyped RF receiving coil group comprises two dull and stereotyped RF receiving coils; Dull and stereotyped RF receiving coil is symmetrically distributed in the both sides of microfluid passage, and the value of N equals the number of microfluid passage, and the value of M is the group number of the corresponding RF receiving coil of each microfluid passage.
5. a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique according to claim 1 is characterized in that: said back up pad (110) is the rectangle thin plate.
6. a kind of micro-fluidic biological detection of particles chip based on nuclear magnetic resonance technique according to claim 1 is characterized in that: said dull and stereotyped radio-frequency sending coil (103) is a plane thread shape structure.
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| CN2010190261138A CN101782539B (en) | 2010-02-05 | 2010-02-05 | Microfluidic biomone detection chip based on nuclear magnetic resonance |
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| CN2010190261138A CN101782539B (en) | 2010-02-05 | 2010-02-05 | Microfluidic biomone detection chip based on nuclear magnetic resonance |
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| CN101782539B true CN101782539B (en) | 2012-05-23 |
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| CN102495091A (en) * | 2011-12-06 | 2012-06-13 | 东南大学 | High-flexibility nuclear magnetic resonance detection chip |
| CN105842269B (en) * | 2016-06-13 | 2018-06-22 | 东南大学 | A kind of device for integrating nmr magnet and popping one's head in |
| CN106153661B (en) * | 2016-06-17 | 2017-11-03 | 东南大学 | A kind of method for the noninvasive magnetic resonance detection of blood pressure and blood lipoid |
| CN107884733A (en) * | 2017-11-06 | 2018-04-06 | 厦门大学 | Integral nuclear magnetic resonance radio-frequency probe front end of 3D printing and preparation method thereof |
| CN109613459B (en) * | 2018-12-06 | 2020-04-10 | 厦门大学 | Micro-fluidic planar gradient coil of superconducting pulse nuclear magnetic resonance spectrometer and mounting bracket |
| CN114527154B (en) * | 2022-02-09 | 2024-02-02 | 国仪量子技术(合肥)股份有限公司 | Method for detecting components of metabonomic sample |
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