CN1259982C - Method of bulk processing micro probe based on three dimensional micro processing technology - Google Patents

Abstract

The invention relates to a method for batch processing micro-probes based on a three-dimensional micro-processing technology, which belongs to the technical field of micro-processing. The specific steps of the present invention are: deposit metal on the substrate as a seed layer; throw photoresist on the deposited seed layer, and perform pre-baking, exposure, post-baking, and development; laser cut the top of the photoresist to obtain a top slope structure; using the photoresist microstructure as a mold to electroform a metal mold; remove the photoresist to obtain a metal mold for replicating microneedles; use the metal mold to replicate polymer microneedles. The invention not only realizes low-cost, batch-scale microneedle processing, but also has a wider range of materials suitable for processing, further broadening the application of the microprobe in the field of biomedicine.

Description

Method for batch processing microprobes based on three-dimensional micromachining technology

technical field

The invention relates to a method for processing microprobes, in particular to a method for batch processing microprobes based on a three-dimensional microfabrication process. It belongs to the technical field of micro processing.

Background technique

Conventional hypodermic injections typically require a needle to penetrate the surface of the skin and deep below the skin to deliver the drug directly into a blood vessel. Therefore, this process is not only accompanied by pain, but also requires some training to master the injection technique. The microneedles only pierce the stratum corneum of the skin surface and no longer go deep, and the medicine enters the blood circulation system through capillaries. Since there are no nerve endings in the stratum corneum, there is no significant pain during the injection. The operation process of the microneedle is also very simple, as long as the needle display is directly pasted on the skin, it is especially suitable for injecting high-efficiency drugs in small doses.

Currently reported microprobe research mainly has three methods. One is to use silicon technology to process silicon microprobes through wet etching or reactive ion etching technology, and the other is to use laser processing, electroplating and wet etching to process metal microneedles. The above two methods have complex processes and processing cycles. The shortcomings of length and high cost are difficult to meet the requirements of biomedical last use. The third is the article titled "Micromachined Biodegradable" published on pages 371 to 374 of "the 16thannual international conference on micro electro mechanical systems" (the 16th International Annual Conference on Micro-Opto-Electromechanical Systems) by Jung-Hwan Park et al. in 2003. Microstructures" (micro-processing biodegradable microstructures), which introduces the use of SU-8 photoresist to prepare a microneedle structure master, then replicates a PDMS mold, and then uses the mold to cast biodegradable microprobes. Although this method can realize the mass production of micro-probes, because the PDMS material is very soft, only the casting method can be used to replicate micro-needles, so the processing time required for replicating micro-needles with it is shorter than that of metal molds The molding process is longer, and the materials suitable for PDMS molds are less than metal molds.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art, to provide a method for batch processing micro-probes based on three-dimensional micro-processing technology, using three-dimensional micro-processing technology and laser cutting technology, electroforming to obtain a metal mold with a slope, using The mold can replicate polymer microprobes with top slopes in batches, so the processing method has the advantages of simple process, short process cycle and low cost.

The present invention is achieved through the following technical solutions, and the concrete steps of the present invention are as follows:

A: Deposit metal on the substrate as a seed layer.

B: Spray the photoresist on the deposited seed layer, and perform pre-baking, exposure, post-baking, and development.

C: Laser cutting the top of the photoresist to obtain the top bevel structure.

D: Electroformed metal mold.

E: Removal of photoresist.

F: Replicating polymer microneedles with a metal mold.

In the invention, the microstructure of the photoresist is photoetched firstly, and after the top slope of the photoresist is cut out by laser, the metal mold is electroformed to replicate the polymer microprobe in batches. The metal can be nickel, iron-nickel alloy or copper etc.

The outer diameter of the microneedle and the diameter of the inner hole of the microneedle are determined by the size of the mask on the photolithography mask. Changing the size of the mask on the mask can obtain microneedles with different outer diameters and inner hole diameters. The microneedles can be A single, or an array. The length of the microneedles depends on the thickness of the photoresist.

The present invention utilizes the laser to cut the top of the photoresist to obtain the top slope structure, so the method only needs to adjust the cutting path of the laser to obtain the top slope of the photoresist with different slopes, correspondingly, microneedles with different top slopes can be obtained.

In step A, the selection of the metal material should fully consider the bonding force with the photoresist to be thrown later. The present invention uses metal titanium, which is oxidized and blackened to improve its bonding force with the photoresist.

In step B, the thickness of the photoresist is determined by the length of the required microneedles, so this method is suitable for processing microneedles of different lengths. When the length of the microneedle is required to be on the order of millimeters, a second layer of glue is thrown on the photoresist that has been post-baked for the first time, and then aligned for exposure, post-baked, and developed together.

In step C, a laser is used to cut the top of the photoresist to obtain a top bevel structure. The cutting path of the laser is controlled according to the required slope of the bevel.

In step D, because the electroforming mold takes a long time, the low-speed and low-stress electroforming process is preferred.

In step E, a photoresist removing solvent is used to remove the photoresist.

In step F, the length of the molding cycle is mainly determined by the two links of heating and cooling. Therefore, the molding temperature and demoulding temperature of the molding material are two key factors. Under the condition of the qualified rate, the lowest possible temperature should be selected. Molding temperature and the highest possible demoulding temperature. The pressure during molding should be as low as possible to reduce mold damage and prolong the service life of the mold. The replicated polymer can be plastic or rubber. The plastic microneedle can be replicated by molding, and the rubber microneedle can be replicated by casting. This method can only be realized through polymerization.

The present invention uses three-dimensional micro-machining technology and laser cutting technology to process metal molds, and then replicates micro-needles to process micro-needles, so it is a batch micro-needle processing method with low processing cost. In addition, it is different from existing processing technology The difference is: (1) Since the microneedle mold processed by this technology is made of metal material, not only the life of the mold is long, but also the range of materials suitable for processing by this technology is wider, which can be used for molding plastic polymers or Cast rubber-like polymers. (2) The top of the photoresist is cut with a laser to obtain the top slope structure, so the method only needs to adjust the cutting path of the laser to obtain the top slope of the photoresist with different slopes, and accordingly microneedles with different top slopes can be obtained .

Description of drawings

Fig. 1 method flowchart of the present invention

Detailed ways

As shown in Figure 1, the following provides an embodiment in conjunction with the specific content of the method of the present invention:

First deposit 2 microns of titanium metal as a seed layer on the silicon substrate, and then carry out oxidation treatment. The specific oxidation process is: dissolve 15 grams of NaOH in 750ml of deionized water. In order to improve the oxidation rate and oxidation uniformity, the oxidation is performed at Carry out in a water bath at 65°C. When the temperature of the water bath reaches 50°C, add 15ml of hydrogen peroxide. When the temperature of the water bath reaches 65°C, put the substrate into it. The oxidation ends in three minutes, and then put it into deionized water to clean the substrate.

Spray 500 microns of SU-8 photoresist on the oxidized and cleaned substrate, and then perform pre-baking. The pre-baking conditions are: bake at 65°C for half an hour, bake at 95°C for 2.5 hours, and then cool with the furnace. The pre-baked substrate is exposed, and the exposure condition is: 4500mJ/cm ² . After exposure, the substrate is post-baked, and the post-baking conditions are: bake at 65°C for half an hour, bake at 95°C for 1 hour, and then cool in the furnace. The post-baked substrate was developed, and the developing condition was 30 minutes.

The 8000 laser system Lpx210i laser source produced by Exitech Company is used to cut at a frequency of 80Hz and a power of 0.4J/cm ² .

The cleanly developed substrate is electroformed, and the conditions for electroforming metal nickel are as follows: the pH value of the electroforming solution is 5, the temperature is 50° C., and the quality of the electroforming metal is better when the electroforming rate is controlled at 14 μm/hour.

Remove the photoresist embedded in the mold with SU-8 adhesive removing solvent.

The PC material microneedle was pressed with a nickel mold, and the molding conditions adopted were: molding temperature 200°C, molding pressure 5000N, molding time 60s, demolding temperature 120°C, demolding speed 0.2 (mm/s).

There are nearly 10,000 microneedles on the metal mold, so many microneedles can be reproduced at one time by molding, realizing batch processing of microneedles. Since the microneedle molds processed by this technology are made of metal materials, not only the mold life is long, but also A wider range of materials are suitable for processing with this technology, both for molded plastic-like polymers and for cast rubber-like polymers.

The present invention utilizes the laser to cut the top of the photoresist to obtain the top slope structure, so the method only needs to adjust the cutting path of the laser to obtain the top slope of the photoresist with different slopes, correspondingly, microneedles with different top slopes can be obtained.

Claims (9)

1, a kind of method based on the batch processing microprobe of three-dimensional micromachining technology, it is characterized in that, comprises the steps: A: Deposit metal on the substrate as a seed layer; B: Throw photoresist on the deposited seed layer, and perform pre-baking, exposure, post-baking, and development; C: laser cutting the top of the photoresist to obtain the top slope structure; D: electroformed metal mold; E: remove photoresist; F: Replicating polymer microneedles with a metal mold. 2. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that firstly, the photoresist microstructure is photoetched, and the metal is electroformed after the laser cuts the top slope of the photoresist. Mold, the mold metal is nickel, iron-nickel alloy or copper. 3. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that the outer diameter of the microneedle and the diameter of the inner hole of the microneedle are determined by the size of the mask on the photolithographic mask plate It is determined that the microneedles are single or arrayed, and the length of the microneedles depends on the thickness of the photoresist. 4. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that the replicated polymer is plastic or rubber, the plastic microneedle is replicated by molding, and the rubber microneedle is replicated by Casting method. 5. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that, in step A, the metal material is metal titanium, which is oxidized and blackened to improve its contact with the photoresist. Binding force. 6. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that, in step B, the thickness of the photoresist is determined by the length of the required microneedle, when the microneedle When the length is required to be on the order of millimeters, the second layer of glue is thrown on the photoresist that has been post-baked for the first time, and then aligned for exposure, post-baked, and developed together. 7. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that, in step C, the top of the photoresist is cut by laser to obtain the top slope structure, only need to adjust the By cutting the path, the top slopes of the photoresist with various slopes are obtained, and the microneedles with corresponding top slopes are obtained. 8. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that in step D, a low-speed and low-stress electroforming process is used. 9. The method for batch processing microprobes based on three-dimensional microfabrication technology according to claim 1, characterized in that, in step E, a solvent for removing photoresist is used to remove the photoresist.

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