CN102994379A - Single-celled graphical chip capable of generating high magnetic field gradients based on magnetic filtering - Google Patents
Single-celled graphical chip capable of generating high magnetic field gradients based on magnetic filtering Download PDFInfo
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- CN102994379A CN102994379A CN2012104792369A CN201210479236A CN102994379A CN 102994379 A CN102994379 A CN 102994379A CN 2012104792369 A CN2012104792369 A CN 2012104792369A CN 201210479236 A CN201210479236 A CN 201210479236A CN 102994379 A CN102994379 A CN 102994379A
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Abstract
The invention discloses a single-celled graphical chip capable of generating high magnetic field gradients based on magnetic filtering, belonging to the technical field of a biological micro-system. The chip is formed by sequentially overlapping a magnetic source, a magnetic filter and a biocompatibility modification layer, wherein the magnetic filter is a permanent magnet with hole arrays. In the chip disclosed by the invention, magnetic trap arrays with high gradients are formed via the magnetic source and the magnetic filter, and then magnetic particles are absorbed towards the center of the trap; once entering the magnetic field, the magnetic particles cannot break away from the restriction of the magnetic field without an enough force; and the diameter of the formed single magnetic trap is close to the diameter of a single cell so that one trap only absorbs one cell and the formed cell arrays are single-celled arrays. According to the invention, the cell patterning efficiency is improved and the cell patterning period is shortened. The most outstanding characteristic of the single-celled graphical chip in the invention is that the fabrication process of the chip is very simple.
Description
Technical field
The invention belongs to the biological micro-systems technical field, be specifically related to a kind of unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering.
Background technology
The data that most of traditional Bioexperiment obtains all are the statistical average results of a large amount of cells.Yet cell has individual otherness owing to the difference of ionic channel state, the dynamic performance of cytoskeleton, the not equal reason of cell interior network.The entrained abundant information of otherness of individual cells has often been ignored in traditional Bioexperiment.Relevant studies show that, the adaptability that cancer cells is powerful and resistance derive from the individual difference of cancer cells, therefore to the specific aim research of heterogeneous cell for probe into cancer cells mechanism, the development cancer therapy drug is most important, is important method and the approach that realizes unicellular heterogeneous detection and cell is patterned into unicellular array.
Based on the graphical chip of the cell of micro-coil array be a kind of based on the MEMS micro-processing technology, have the chip of graphical micro-coil array, it has large, the graphical efficient high of field gradient.Its principle of work is as follows: utilize graphical micro-coil array to form gradient magnetic, magnetic induction density is large namely can produce one in coil region in the middle of, the magnetic field that peripheral magnetic induction density reduces gradually, such magnetic field will look like an invisible cage, with magnetic-particle to central suction, in a single day magnetic-particle enters inside, magnetic field, if there is not enough power just can't make it break away from the constraint in this magnetic field.And we can connect upper magnetic-particle by ad hoc approach with cell, can be with cell and magnetic-particle as a magnetic integral body (we grasp this method), so we can catch cell by the graphical gradient magnetic that patterned little coil forms, thereby realize the graphical of cell.
In recent years along with the high speed development of minute manufacturing technology, utilize the chip lab of minute manufacturing fabrication techniques to become the instrument of Single cell analysis of future generation.Present unicellular array means mainly are divided into two classes: a class is to utilize biological chemistry means extracellular matrix, polypeptide or other polymkeric substance on substrate to carry out graphically, cause cell to the difference of the affinity of different positions on the substrate, thereby realize graphical.The Dino Di Carlo of University of California Berkeley in 2006, the human PDMS such as Liz Y. Wu have made a cover microfluid system and have come cell is tackled, thereby form unicellular array; Easily cause distortion and the apoptosis of cell because these class methods are limited in cell on the substrate, be not suitable for diagnosis and cell performance analysis.
Another kind of is the method for utilizing physics, such as methods such as microfluid, dielectrophoresis, little magnetic fields cell is positioned.The people such as M. Fre ' ne ' a in 2003 have utilized negative dielectrophoresis principle design one cover microelectrode array has been realized unicellular location.These methods are less to the harm of cell, and conveniently carry out medical diagnosis on disease, the operations such as drug screening and cell performance analysis, but only realized cellular localization, do not realize unicellular graphical.
Simultaneously, the graphical device that utilizes micro-coil array to form is arranged also now, but its based on MEMS manufacture craft relative complex.
Summary of the invention
The object of the invention is to overcome at present unicellular graphical chip fabrication technique problem complicated, that operation easier is large a kind of unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering is provided.
A kind of unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering is stacked gradually by magnetic source, magnetic filter and bio-compatibility decorative layer and to form, and described magnetic source is that magneticstrength is greater than the permanent magnet of 0.2T; Described magnetic filter is the ferro-magnetic with array of orifices; Described bio-compatibility decorative layer is titanium dioxide, silicon-dioxide, polyethylene, poly(lactic acid), poly-acid anhydrides, PHA or polyamino acid.
The diameter of the single aperture of described array of orifices is 1 μ m-15 μ m.
Beneficial effect of the present invention is to utilize magnetic source and magnetic filter to form the very high pyrotron array of gradient, magnetic-particle is attracted to Trapping Centers, in a single day magnetic-particle enters inside, magnetic field, if there is not enough power just can't make it break away from the constraint in this magnetic field, and the single pyrotron size that forms approaches with the individual cells diameter, only attract a cell so satisfy a pyrotron, guarantee that the cellular array that forms is unicellular array.This invention has improved the patterned efficient of cell, shortens the patterned cycle of cell, and the characteristics of giving prominence to the most are that the manufacture craft of this chip is very simple.
Description of drawings
Fig. 1 is chip one-piece construction synoptic diagram;
Fig. 2 is magnetic filtering device synoptic diagram;
Fig. 3 is that magnetic core logical circuit deflection filters synoptic diagram;
Fig. 4 is magnetic induction line law of refraction synoptic diagram;
Wherein each label is: 1-magnetic source, 2-magnetic filtering device, 3-bio-compatibility decorative layer, 4-array of orifices.
Embodiment
Below in conjunction with accompanying drawing, preferred embodiment is elaborated.
The unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering that the present invention proposes is comprised of magnetic source, magnetic filter and bio-compatibility decorative layer, and shown in Fig. 1-2, wherein magnetic source is made by neodymium iron boron, and the diameter of array of orifices is 10 μ m.The bio-compatibility decorative layer is titanium dioxide, can guarantee that absorption cytoactive thereon is not affected.
Theoretical according to the magnetic field boundaries condition: if above magnetic source 1, add the high ferro-magnetic 2 with array of orifices 4 of a relative magnetic permeability, because magnetic induction line enters the high medium of relative magnetic permeability by the low medium of relative magnetic permeability, magnetic induction line can be to boundary deflection after can entering the high medium of relative magnetic permeability, the relative magnetic permeability of aperture 4 is very low, the relative magnetic permeability of ferro-magnetic 2 is very high, then the ferro-magnetic 2 with array of orifices 4 can produce deviation to magnetic induction line, the magnetic field deviation as shown in Figure 3, from the result, ferro-magnetic 2 with array of orifices 4 plays the magnetic filtering effect, direction is directly passed towards the magnetic induction line of aperture 4, influenced hardly, and the magnetic induction line that will pass ferro-magnetic 2 will by deviation, as shown in Figure 4, will be limited in the ferro-magnetic, so very large in array of orifices 4 borderline region internal magnetic field intensity, and very little in aperture border foreign field intensity, almost nil, so can form the magnetic field of high-gradient by magnetic source and magnetic filter.Can form the pyrotron array about diameter 10 μ m, and magnetized particles is very big at the magnetic force that the pyrotron edge is subject to, can guarantee that cell can be in bond, and the cage center is subjected to magnetic force hardly, on not impact of cell.This is by following theory support: when paramagnetic material did not reach the magneticsaturation state, the magnetic force size that paramagnetic material is subject in a vacuum was shown in formula (1-1).
Wherein χ is susceptibility; V is the paramagnetic material volume; μ
0Be permeability of vacuum; B is magnetic induction density;
Be the magnetic induction density gradient.When paramagnetic material reached the magneticsaturation state, its specific magnetising moment was a constant, and the variation with magnetic induction density does not change, and this moment, the magnetic force size was directly proportional with the gradient of magnetic induction density, shown in formula (1-2).
Wherein m is the specific magnetising moment;
Be the magnetic induction density gradient.More than magnetic force F in two formulas
MBe vector with magnetic induction density B, magnetic force direction is consistent with the direction of magnetic induction density gradient, points to | the direction that the B| value is large.
Utilize magnetic source and magnetic filter to form the very high pyrotron array of gradient, magnetic-particle is attracted to Trapping Centers, in a single day magnetic-particle enters inside, magnetic field, if there is not enough power just can't make it break away from the constraint in this magnetic field, and the single pyrotron size that forms approaches with the individual cells diameter, only attract a cell so satisfy a pyrotron, guarantee that the cellular array that forms is unicellular array.This invention has improved the patterned efficient of cell, shortens the patterned cycle of cell, and the characteristics of giving prominence to the most are that the manufacture craft of this chip is very simple.
The said chip making step:
Step 1: with the ferromagnetic layer of MEMS technique making with array of orifices;
Step 2: the compatible film of sedimentary organism on ferromagnetic layer;
Step 3: will be with ferro-magnetic and the permanent magnet bonding of bio-compatibility film.
Claims (2)
1. a unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering is characterized in that, is stacked gradually by magnetic source, magnetic filter and bio-compatibility decorative layer to form, and described magnetic source is that magneticstrength is greater than the permanent magnet of 0.2T; Described magnetic filter is the ferro-magnetic with array of orifices; Described bio-compatibility decorative layer is titanium dioxide, silicon-dioxide, polyethylene, poly(lactic acid), poly-acid anhydrides, PHA or polyamino acid.
2. the described unicellular graphical chip that forms high magnetic field gradients based on magnetic filtering according to claim 1 is characterized in that the diameter of the single aperture of described array of orifices is 1 μ m-15 μ m.
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| CN201210479236.9A CN102994379B (en) | 2012-11-22 | 2012-11-22 | Single-celled graphical chip capable of generating high magnetic field gradients based on magnetic filtering |
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| CN201210479236.9A CN102994379B (en) | 2012-11-22 | 2012-11-22 | Single-celled graphical chip capable of generating high magnetic field gradients based on magnetic filtering |
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| CN102994379A true CN102994379A (en) | 2013-03-27 |
| CN102994379B CN102994379B (en) | 2014-07-23 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030022370A1 (en) * | 2001-07-27 | 2003-01-30 | Rocco Casagrande | Magnetic immobilization of cells |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030022370A1 (en) * | 2001-07-27 | 2003-01-30 | Rocco Casagrande | Magnetic immobilization of cells |
Non-Patent Citations (1)
| Title |
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| DAVID W. INGLIS ET AL.: "Microfluidic high gradient magnetic cell separation", 《JOURNAL OF APPLIED PHYSICS》 * |
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