CN102556931B - Microelectrode array with electrode point distance capable of exceeding micromaching precision and preparation method of microelectrode array - Google Patents
Microelectrode array with electrode point distance capable of exceeding micromaching precision and preparation method of microelectrode array Download PDFInfo
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- CN102556931B CN102556931B CN201110428382.4A CN201110428382A CN102556931B CN 102556931 B CN102556931 B CN 102556931B CN 201110428382 A CN201110428382 A CN 201110428382A CN 102556931 B CN102556931 B CN 102556931B
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Abstract
The invention discloses a microelectrode array with an electrode point distance capable of exceeding micromaching precision and a preparation method of the microelectrode array; the microelectrode array comprises a microelectrode array structural layer, an electrode circuit layer and a microelectrode array covering layer, wherein at least two rows of electrode points which are arranged closely and reach a micromaching precision distance are arranged in the electrode circuit layer, the at least two rows of electrode points are cut into two modules capable of sliding relatively, namely a first microelectrode array module and a second microelectrode array module, the two modules slide relatively to form a shorter electrode point distance. In the invention, a distance among the electrode points for addressing specifically can be changed into 0.866 than the original distance to a minimum extent during relatively sliding of the two modules, so that higher resolution factor is achieved, and furthermore, better electrophysiological acquisition and stimulation effects are achieved. Moreover, the electrode point distance can be properly increased through a proper sliding distance, so that the microelectrode array can be utilized repeatedly, and the electrophysiological acquisition and stimulation can be performed in other electrode point distances.
Description
Technical field
What the present invention relates to is a kind of microelectrode array of medical equipment technical field, and specifically a kind of electrode points spacing towards electric physiology application can exceed microelectrode array of micro-machining accuracy and preparation method thereof.
Background technology
In recent years, along with the continuous progress of MEMS (MEMS:Micro-Electro-Mechanical Systems) technology, the micro-system such as microelectronic device and microsensor range of application is constantly expanded, be widely used in multiple fields, particularly medical domain.
Microelectrode array is to utilize the typical case application of micro electro mechanical system (MEMS) technology at biomedical aspect.Microelectrode array is the electrode of arranging in substrate surface lattice-like, common electrode points diameter minimum is 50 μ m, electrode points spacing minimum is 100 μ m, and in vitro tissue, cell or section are directly closely placed on microelectrode array, extracellular field potential signal that can the multiple sites of synchronous recording.Microelectrode array both can record and also can be used as stimulating or ground connection, was applicable to electrophysiological characteristics and the ion channel biological characteristic research of the excitable cells such as neural and myocyte.
Traditional microelectrode array comprises the sputter, graphical of precious metal material, the deposition of electric barrier material, opening of electrode points etc.But the electrode points spacing of microelectrode prepared by this method is fixed, if need to change scope and the precision of microelectrode recording or stimulation, need again to prepare.And the spacing that some situation need to be adjusted electrode points obtains more excellent record or effect of stimulation, this be also traditional constant spacing electrode can not.Moreover, be limited to the machining accuracy of current micro fabrication, the limit of electrode points spacing can only be to be more than or equal to machining accuracy, if still utilize the electrod-array of variable spacing, just can construct the electrode points spacing that exceedes machining accuracy, this exceeds traditional constant spacing electrode ability.
Through the retrieval of prior art is found, Merriam, S.M.E., the people such as O.Srivannavit are at Journal of Microelectromechanical Systems 20 (3): 594-600, 2011 write articles " AThree-Dimensional 64-Site Folded Electrode Array Using Planar Fabrication " (plane preparations of a kind of three-dimensional 64 collapsible electrod-arrays), this technology adopts sputter, the traditional handicrafts such as etching have realized two plane electrodes with probe, wherein on each probe, there are four electrode points, and these two plane electrodes can fold and then form stereo electrod.This is a kind of quite complicated electrode structure, but the relative position of four electrode points on its each probe but fix, can not adapt to the actual conditions that electrode points changes apart from needs.So in actual use, kind electrode flexibility deficiency, should use and be subject to more restriction.
Chinese Patent Application No. is 201110110285.0, publication number is CN 102178998A, the three-decker that discloses microelectrode array in this patent is microelectrode array structure sheaf, telegraph circuit layer, microelectrode array cover layer, wherein: telegraph circuit layer is clipped in the middle by microelectrode array structure sheaf and microelectrode array cover layer.But the electrode points spacing that does not also disclose this microelectrode array is also adjustable.
U.S. Patent number: US7,501,301, " Low cost fabrication of microelectrode arrays for cell-based biosensors and drug discovery methods " (low cost microelectrode array preparation) taking cell as basic biology sensor and drug discovery method, this technology discloses a kind of relating to and has utilized printed circuit board (PCB) (PCB) manufacturing process and the material of non-modified to carry out the method that low cost is prepared microelectrode array.This microelectrode array is made up of the coated patterned conducting wire of thin polymer film, and can have a lot of application at biology sensor and drug discovery field.But the electrode points spacing of this microelectrode array is fixed.For example can not change by changing electrode points spacing some performance of biology sensor.
U.S. Patent number: US6,896,780, " Microelectrode; microelectrode array and method for manufacturing the microelectrode " (preparation method of microelectrode and microelectrode array), this technology discloses and has a kind ofly related to method prepared by microelectrode and microelectrode array, and the temperature of this microelectrode is controlled.This microelectrode, by forming heat isolation in an annular seal space on silicon substrate, has a micro-heater in annular seal space, electrode can indirectly be heated by micro-heater.But the electrode points spacing of this microelectrode array is also fixed.
To sum up, although the preparation method of microelectrode array has obtained more detailed research, and the relevant extension function of microelectrode array has also obtained certain attention, but in document, have no report electrode points adjustable interval, even can exceed the microelectrode array of micro-machining accuracy.
Summary of the invention
The present invention is directed to prior art above shortcomings, provide a kind of electrode points spacing towards electric physiology application can exceed microelectrode array of micro-machining accuracy and preparation method thereof, easy and simple to handle, can make microelectrode array reasonably be reused.And the microelectrode array that can construct the electrode points spacing that exceedes micro-machining accuracy, obtains higher resolution ratio, further obtain more excellent record or effect of stimulation.
The present invention is achieved by the following technical solutions:
Electrode points spacing of the present invention can exceed the microelectrode array of micro-machining accuracy, comprise: the microelectrode array structure sheaf that sets gradually and form composite construction, telegraph circuit layer and microelectrode array cover layer, microelectrode array cover layer directly contacts with tissue to be measured, in telegraph circuit layer, be provided with at least two row close-packed arrays and reach the electrode points of micro-machining accuracy spacing, described electrode points is divided into the module of two energy relative slidings, i.e. the first microelectrode array module and the second microelectrode array module, when this two parts relative sliding, form less electrode points spacing.
Described microelectrode array cover layer is covered on microelectrode array structure sheaf except electrode points is with external position.
Described the first microelectrode array module and the second microelectrode array module are attached in hard substrate.
The radius of described microelectrode array electrode points is the full accuracy in the micro-process of this microelectrode array, refers to the circle of the diameter minimum that can obtain in photoetching process, and scope is 0.01 μ m-100 μ m.
The center of the electrode points in two described microelectrode array modules forms the summit of equilateral triangle.
Distance between described adjacent electrode dot center, scope is 0.04 μ m-400 μ m.
Distance between the adjacent electrode dot center of minimum range between described electrode points before sliding becomes 0.866 times of this distance.
In described telegraph circuit layer, only electrode points directly contacts and participates in electric physiology collection, stimulation with tissue to be measured.
The described electrode points that reaches micro-machining accuracy spacing refers to and the spacing of electrode points in telegraph circuit layer has reached the limit of certain micro-machining accuracy (for example 10 μ m).
The present invention utilizes the cooperation each other of these electrode points to obtain the electrode points spacing of the limit that exceedes this micro-machining accuracy, be specially the compact arranged electrode points of two row is divided into two parts, then make this two parts relative sliding and then produce less electrode points spacing.When relative sliding, utilize outside micromotion structure to guide this two parts parallel sliding, avoid at the square upward sliding perpendicular to electrode plane as far as possible, thus the precision of guarantee electrode points spacing.
Electrode points spacing of the present invention can exceed the preparation method of the microelectrode array of micro-machining accuracy, specifically comprises the steps:
First positive-glue removing graphical on Si sheet, sputter noble metal Seed Layer, adopts Lift-off technique to remove photoresist, and graphical Seed Layer, forms telegraph circuit layer;
And then deposition Parylene-C, for the second time photoetching offset plate figure, use reactive ion etching (RIE) that Parylene-C is carved and worn, expose electrode points, form microelectrode array cover layer;
The substrate of Si sheet, as structure sheaf, is used Ultra-Violet Laser that microelectrode array is cut into two modules between the compact arranged electrode points of two row, facilitates the relative sliding of these two modules.
In said method, the part that cutting process also can be used as in reactive ion etching step completes.
In said method, two sliding blocks also can independently be prepared by identical method.
The present invention utilizes in two module relative sliding processes, and for the electrode points of addressing, specific, its electrode points spacing can minimum become original 0.866 times, obtains higher resolution ratio, and then obtains better electric physiology collection and effect of stimulation.In addition, by suitable sliding distance, can also increase electrode points spacing, this microelectrode array can be reused, carry out electric physiology collection and stimulation in other electrode points spacing.
To sum up, the present invention is simple in structure, easy to use, only need to be according to application background microelectrode array two parts relative sliding when use, the electrode points spacing that exceedes this micro-machining accuracy limit that just can obtain, and then obtain higher resolution ratio, realize collection and the stimulation of better electricity physiological signal.
Brief description of the drawings
Fig. 1 is the structural representation of one embodiment of the invention.
Detailed description of the invention
Below embodiments of the invention are elaborated, the present embodiment is implemented as prerequisite taking technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
The concrete preparation process of described microelectrode array is as follows:
First the positive glue that gets rid of 5 μ m on Si sheet is also graphical, sputter noble metal (comprising Pt, Ir, Au etc.) Seed Layer, and 100-15000 dust, adopts Lift-off technique to remove photoresist, and graphical Seed Layer, forms telegraph circuit layer;
And then the Parylene-C of deposition 5 μ m, for the second time photoetching offset plate figure, use reactive ion etching (RIE) that Parylene-C is carved and worn, expose electrode points, form microelectrode array cover layer;
The substrate of Si sheet, as structure sheaf, is used Ultra-Violet Laser that microelectrode array is cut into two modules between the compact arranged electrode points of two row, facilitates the relative sliding of these two modules.
In the present embodiment, the part that cutting process also can be used as in reactive ion etching step completes.
In the present embodiment, these two sliding blocks also can independently be prepared by identical method.
Embodiment 2
As shown in Figure 1, in figure: the first microelectrode array module 1 of well cutting, the second microelectrode array module 2 of well cutting,, distance 7 between circle 6, adjacent electrode dot center, high by 8, in hang down point 9, electrode points center with in the hang down distance 10 of point.
The present embodiment comprises: the microelectrode array structure sheaf, telegraph circuit layer and the microelectrode array cover layer that set gradually and form composite construction, microelectrode array cover layer directly contacts with tissue to be measured, is provided with at least two row close-packed arrays and reaches the electrode points of micro-machining accuracy spacing in telegraph circuit layer.Three electrode points of described electrode points 3,4,5 are divided into the module of two energy relative slidings, i.e. the second microelectrode array module 2 of the first microelectrode array module 1 of well cutting, well cutting forms less electrode points spacing when this two parts relative sliding.
In the present embodiment, described two electrode points 3,4 are in the first microelectrode array module 1 of well cutting, and another electrode points 5 is in the second microelectrode array module 2 of well cutting.The first microelectrode array module 1 of described well cutting and the second microelectrode array module 2 of well cutting are attached in hard substrate, facilitate relative sliding and insertion to organize depths.
In the present embodiment, the radius of first described electrode points 3 is the full accuracy (referring generally to the circle of the diameter minimum that can obtain in photoetching process) in the micro-process of this microelectrode array, and common scope is 0.01 μ m-100 μ m.
In the present embodiment, the center of described three electrode points 3,4,5 forms the summit of equilateral triangle.
In the present embodiment, described circle 6 referred to the circle at other the electrode points center nearest apart from electrode points 3 centers, and in micro-process, the circle that the center of other complete electrode points forms can appear in distance electrode points 3 centers.
In the present embodiment, the distance 7 between described adjacent electrode dot center refers to the radius of circle 6, and common scope is 0.04 μ m-400 μ m.
In the present embodiment, described high 8 refer to the leg-of-mutton height being made up of three nearest electrode points centers.
In the present embodiment, the point 9 that hangs down in described refers in be made up of three nearest electrode points centers leg-of-mutton the point that hangs down.
In the present embodiment, described microelectrode array cover layer is covered on microelectrode array structure sheaf except electrode points is with external position.
In the present embodiment, described telegraph circuit layer is by electrode points, connecting line and form with the tie point of peripheral circuit.
In the present embodiment, the length x width x thickness of described microelectrode array structure sheaf is 5 × 5 × 0.001mm-150 × 150 × 1mm.
In the present embodiment, in described telegraph circuit layer, connecting live width is 10nm-1000 μ m; The cross-sectional area of electrode points is 1 μ m
2-10000 μ m
2.
In the present embodiment, in described telegraph circuit layer, only electrode points directly contacts and participates in electric physiology collection, stimulation with tissue to be measured.
In the present embodiment, the tectal length x width x thickness of described microelectrode array is 5 × 5 × 0.001mm-150 × 150 × 1mm.
The operation principle of the present embodiment is: in order to obtain the electrode points spacing of the full accuracy exceeding in micro-process, the second microelectrode array module 2 of well cutting is slided left with respect to the first microelectrode array module 1 of well cutting, second and third electrode point 4 and 5 between pitch smaller, and hang down and reach minimum while putting 9 in the center of electrode points 5 arrives, distance 7 between the adjacent electrode dot center of minimum range between electrode points before sliding becomes 0.866 times of this distance, high by 8.Sliding distance in whole sliding process be electrode points center with in the hang down distance 10 of point.If the addressing that keeps electrode points second and third electrode point 4 and 5 between, continue slip by the larger electrode points spacing of acquisition.In addition, if the addressing of electrode points change into first and third electrode point 3 and 5 between, so only the direction of relative sliding need to be changed into the right.
As shown in table 1, it is as shown in the table for the application request size used of the present embodiment.
One group of modular design parameter of the microelectrode array of table 1 electrode points adjustable interval
| Microelectrode array structure sheaf (length x width x thickness) (mm) | 50×50×0.005 |
| Microelectrode array cover layer (length x width x thickness) (mm) | 50×50×0.005 |
| (μ m) for the radius of electrode points 3 | 5 |
| (μ m) for the minimum diameter of a circle that can obtain in photoetching process | 10 |
| (μ m) for the radius of circle 6 | 20 |
| (μ m) for distance 7 between adjacent electrode dot center | 20 |
| High 8 (μ m) | 17.32 |
| Electrode points center with in hang down point distance 10 (μ m) | 10 |
As can be seen from the above embodiments, the microelectrode array that the present invention utilizes electrode points spacing can exceed micro-machining accuracy carries out collection and the stimulation of electricity physiological signal, with respect to the microelectrode array of traditional constant spacing, only two of this microelectrode array module relative sliding just can need to be obtained to the microelectrode array that electrode points spacing exceedes micro-machining accuracy, obtain higher resolution ratio, and then obtain better electric physiology collection and effect of stimulation.In addition, by suitable sliding distance, can also increase electrode points spacing, this microelectrode array can be reused, carry out electric physiology collection and stimulation in other electrode points spacing.
Although content of the present invention has been done detailed introduction by above preferred embodiment, will be appreciated that above-mentioned description should not be considered to limitation of the present invention.Read after foregoing those skilled in the art, for multiple amendment of the present invention and substitute will be all apparent.Therefore, protection scope of the present invention should be limited to the appended claims.
Claims (9)
1. an electrode points spacing can exceed the microelectrode array of micro-machining accuracy, comprise: the microelectrode array structure sheaf, telegraph circuit layer and the microelectrode array cover layer that set gradually and form composite construction, described microelectrode array cover layer directly contacts with tissue to be measured, in telegraph circuit layer, be provided with at least two row close-packed arrays and reach the electrode points of micro-machining accuracy spacing, and the center of electrode points forms the summit of equilateral triangle; It is characterized in that, the compact arranged electrode points of described at least two row is cut into the module of two energy relative slidings, i.e. the first microelectrode array module and the second microelectrode array module forms less electrode points spacing when this two modules relative sliding.
2. electrode points spacing according to claim 1 can exceed the microelectrode array of micro-machining accuracy, it is characterized in that, described the first microelectrode array module and the second microelectrode array module are attached in hard substrate.
3. electrode points spacing according to claim 1 can exceed the microelectrode array of micro-machining accuracy, it is characterized in that, the radius of described microelectrode array electrode points is the full accuracy in the micro-process of this microelectrode array, refer to the circle of the diameter minimum that can obtain in photoetching process, scope is 0.01 μ m-100 μ m.
4. electrode points spacing according to claim 3 can exceed the microelectrode array of micro-machining accuracy, it is characterized in that, and the distance between the center of adjacent described electrode points, scope is 0.04 μ m-400 μ m.
5. electrode points spacing according to claim 1 can exceed the microelectrode array of micro-machining accuracy, it is characterized in that, the minimum range between described electrode points is 0.866 times of distance between the adjacent electrode dot center before sliding.
6. electrode points spacing according to claim 1 can exceed the microelectrode array of micro-machining accuracy, it is characterized in that, described microelectrode array cover layer is covered on microelectrode array structure sheaf except electrode points is with external position.
7. the electrode points spacing as described in claim 1-6 any one can exceed the preparation method of the microelectrode array of micro-machining accuracy, it is characterized in that, comprises the steps:
First positive-glue removing graphical on Si sheet, sputter noble metal Seed Layer, adopts Lift-off technique to remove photoresist, and graphical Seed Layer, forms telegraph circuit layer;
And then deposition Parylene-C, for the second time photoetching offset plate figure, use reactive ion etching that Parylene-C is carved and worn, expose electrode points, form microelectrode array cover layer;
The substrate of Si sheet, as structure sheaf, is used Ultra-Violet Laser that microelectrode array is cut into two modules between the compact arranged electrode points of two row, facilitates the relative sliding of these two modules.
8. electrode points spacing as claimed in claim 7 can exceed the preparation method of the microelectrode array of micro-machining accuracy, it is characterized in that, described cutting process completes as the part in reactive ion etching step.
9. electrode points spacing can exceed the preparation method of the microelectrode array of micro-machining accuracy as claimed in claim 7 or 8, it is characterized in that, described two sliding blocks are independently prepared by identical method.
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| CN2510084Y (en) * | 2001-12-11 | 2002-09-11 | 王绪畅 | Ultrashort wave electrode seat |
| CN2902191Y (en) * | 2006-01-25 | 2007-05-23 | 中国医学科学院生物医学工程研究所 | Electrode array sensor used for electrical impedance imaging |
| GB2471873A (en) * | 2009-07-15 | 2011-01-19 | Wzvi Ltd | Electrode array arranged on a triangular grid for electrical impedance imaging |
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| JP2002208718A (en) * | 2001-01-09 | 2002-07-26 | Canon Inc | Photovoltaic element and solar cell module |
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| CN2510084Y (en) * | 2001-12-11 | 2002-09-11 | 王绪畅 | Ultrashort wave electrode seat |
| CN2902191Y (en) * | 2006-01-25 | 2007-05-23 | 中国医学科学院生物医学工程研究所 | Electrode array sensor used for electrical impedance imaging |
| GB2471873A (en) * | 2009-07-15 | 2011-01-19 | Wzvi Ltd | Electrode array arranged on a triangular grid for electrical impedance imaging |
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