CN103829954B - A kind of adhesive type empty micropin array and manufacture method thereof - Google Patents

Abstract

The present invention provides an adhesive-type hollow microneedle array, which comprises a high-strength hard plate, a group of hollow microneedle arrays are arranged on the front of the plate, the length of the microneedles is 0.1-3mm, and an elastic cavity is arranged on the back of the plate, so that The cavity is connected with the cavity of the microneedle head, and the preparation method is as follows: the hollow metal microneedle array is lubricated and pierced into the viscous fluid elastic polymer prepolymer, and vacuumized; after heating and curing, the solid elastic polymer and the The metal is separated to obtain an elastic template with an array of pits; the thermoplastic material is covered with the elastic template and heated and melted into a viscous fluid state, and then pressed to shape; separated after cooling, a hard plate containing a microneedle array is obtained; glued to the back of the plate The sticky hollow microneedle array device is obtained by connecting the elastic cavity. The invention has the advantages of simple and fast manufacturing process, low cost, reusable templates, batch production of products, simple and quick operation, and is widely used in the fields of body fluid collection, transdermal drug delivery, allergen testing, biomedical electrodes and skin beauty.

Description

A paste-type hollow microneedle array and its manufacturing method

technical field

The invention relates to the field of microarrays, in particular to an adhesive-type hollow microneedle array and a manufacturing method thereof.

Background technique

Today's clinical biochemical detection and treatment are based on the collection of body fluids (especially whole blood) and the delivery of drugs. It is extremely important to establish a safe, effective, and low-burden body fluid exchange mode for patients. Existing body fluid exchange methods are mainly divided into: injection needle type, lancet type, and laser type. Laser blood collection instrument is a medical instrument that uses laser pulses to take peripheral blood from patients. The blood collection method is painless and safe, but requires professional small and medium-sized instruments. It is to puncture the skin and squeeze the puncture, and obtain a blood sample from the extruded droplet, because it will contaminate the sample when it is exposed to the air; the injection needle is to draw or inject into the vein through subcutaneous injection by venipuncture Operation; the latter two methods will cause greater pain to the patient, and also cause many people, especially children, to have a sense of fear, and its operation also requires certain work experience.

In order to solve such problems, some related patents have appeared, such as the painless blood collection needle with the Chinese national patent application number CN201120424868. The medical painless blood collection microneedle chip and its preparation method are more complicated and costly, and the array idea is not used to improve efficiency; for example, a microneedle massager with the patent number CN200710115834.7 and its production method are just a kind of The roller-type microneedle array cannot directly communicate with the internal and external environment. Because it is a solid microneedle, the same aperture is more traumatic.

Contents of the invention

In order to solve the deficiencies of the prior art and create a more simple and effective body fluid exchange mode that can be realized through pasting operations, the present invention firstly provides a paste-type hollow microneedle array, which includes a flat plate on which a group of hollow microneedles are arranged. Microneedles, the length of the hollow microneedles is 0.1-3 mm, the flat plate is provided with a cavity, and the cavity communicates with the cavity of the microneedles.

The cavity is under negative pressure or loaded with medicine.

The flat plate is covered with several hollow microneedles.

The diameter of the hollow microneedle is 200nm-0.8mm.

Further provide a kind of preparation method of above-mentioned paste-type hollow microneedle array, comprise the following steps:

S1. Take the microneedle array, lubricate the microneedle array with lubricant,

S2. Mix A and B components of polydimethylsiloxane in a weight ratio of 1:10=A:B, stir, and preheat to obtain a mixed solution.

S3. Slowly insert the microneedle array obtained in S1 into the mixed solution obtained in S2, fix and vacuumize,

Curing, demoulding, polydimethylsiloxane mold,

S4. Under the condition of keeping the center column vertical, spread the polystyrene powder in the concave area in the center of the mold, clamp the upper and lower sides of the mold with two flat weights, and place it at 200~230 35~50min in muffle furnace at ℃;

S5. Cooling and solidification to obtain polystyrene micro-nano needle arrays,

S6. Prepare a concave elastic polydimethylsiloxane cavity, and stick it to the back of the polystyrene micro-nano needle array to obtain an adhesive blood collection device.

The preheating in step S2 is to place in an oven at 70°C for 6.5-7.5 minutes or in an oven at 80°C for 1.5-2 minutes.

The microneedle array described in step S3 is slowly inserted into the mixed solution for 2-3mm, and the curing described in step S3 is placed in an oven at 70°C for 8-12 minutes or placed in an oven at 80°C for 4-6 minutes.

The length of the center column of the polydimethylsiloxane mold obtained in step S3 is 0.1-3 mm.

The polydimethylsiloxane mold obtained in step S3 can be used repeatedly.

According to the requirements, an application of the above-mentioned adhesive hollow microneedle array in the preparation of bioelectrode, drug-loaded or body fluid collection devices is provided.

The present invention intends to create a more convenient exchange mode between the internal environment of the human body and the outside world (mainly blood sample collection and transdermal drug delivery), and provide a low-cost "operating platform" for it. With a simple sticking operation, the vacuum or other substances in the negative pressure cavity are exchanged with human body fluids through numerous micropores.

The present invention will be oriented to more general daily life and wider groups of people (age or occupation), and contribute to family medicine, personal care and the like. For example, patients with diabetes who need regular blood tests at home or other places can obtain blood samples through a simple "one-stick-one-tear" operation instead of using injection needles or lancets to avoid pain or Contamination of blood samples; innovating related technologies in the fields of medical treatment and cosmetology. For example: in skin beauty technology, the present invention can connect the internal and external environment of the surgical site, eliminate toxins, introduce nutrients or other operations; it can also be combined with gene chip microarray technology in the cavity behind each needle of the blood collection microneedle array Different detection substances can be stored in the computer, and multiple detections can be performed at the same time, and it is expected to be applied in blood testing and allergen testing.

The present invention has the following advantages:

1. The present invention is different from common syringes or lancets that can only artificially control the penetration depth. The sticky blood collection device of the present invention determines the penetration depth by its own specifications. Anyone can complete the blood collection work by performing a simple paste operation through the device, which greatly reduces its use requirements and almost zero threshold.

2. The present invention is different from the blood pricking type (or blood purging type) and the injection type, and the pasting type is a brand-new way of communicating between the internal environment of the human body and the outside world. Through the pores opened by countless tiny (micron or even nanometer) needles, the cavity attached to the blood collection device outside the body fluid environment is connected, and then through negative pressure or capillary action, the efficient and gentle communication between the internal environment of the human body and the outside world is completed.

3. The present invention strengthens the function of the microneedles through an array method, and on the premise of ensuring the flow rate (efficiency), slows down the pressure of the blood/drug flow on the human body.

4. The present invention can be combined with microarray technology to realize the integration of different functions, and can realize the integration of different detection functions, and can be applied in the detection field with high sensitivity and multiple detections, such as skin test for allergens.

5. The operation of the present invention is simpler and more efficient, and only needs a simple "stick and tear" operation; compared with laser blood collection, the manufacturing cost is lower, and it is more widely used in daily life; it is compatible with injection needles and lancets In comparison, it is milder, (1) the needle is tiny, the opening is extremely thin, and the skin is less damaged; (2) through the close contact with the skin, the skin surface is used as the base plane, and the penetration depth of the needle is the length of the needle , by selecting the specifications of the blood drawer instead of manual operation, the penetration depth can be precisely adjusted to prevent irritation or penetration of major (large) nerves or blood vessels, thereby reducing pain and damage to blood vessels; (3) through the array Numerous tiny needles can reduce the pressure during drug delivery or blood sample collection under the premise of ensuring flow.

Description of drawings

Fig. 1 is the structural diagram of embodiment 1.

Fig. 2 is the structural diagram of embodiment 2.

Fig. 3 is the production flowchart of embodiment 1.

Fig. 4 is the production flowchart of embodiment 2.

In Figure 3 and Figure 4, 1 is the metal needle, 2 is molten PDMS, 3 is solidified PDMS, 4 is molten PS, and 5 is solidified PS.

Fig. 5 is a physical picture of the needle head of the final product of the paste-type microneedle array.

detailed description

The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments. Unless otherwise specified, the reagents, equipment and methods used in the present invention are commercially available reagents, equipment and routinely used methods in this technical field.

Embodiment 1 Negative pressure blood collection/transdermal administration patch

The prepared finished product is shown in Figure 1, and the preparation process is shown in Figure 3.

1. Lubrication of the needle body: Lubricate the inner wall of the metal microneedle array and the rough front surface with vaseline or other lubricants;

2. Preheating treatment: Mix A and B components of polydimethylsiloxane (PDMS) in a mass ratio of 1:10=A:B, and put them in a 70°C oven after fully stirring and removing the air 6.5~7.5min (or 80℃, 1.5~2min);

3. Fix the microneedles: slowly insert the metal hollow microneedle array into the PDMS that is still in liquid state, and then fix the whole device after the rough front surface is immersed in the PDMS mixture for 2~3mm;

4. Vacuum pumping: vacuum the whole device with a vacuum pump for 0.5~1min;

5. Heat curing: Put the whole device in an oven at 70°C until it is completely cured, about 8~12min (or 80°C, 4~6min);

6. Pull out the microneedles: separate the cured PDMS mixture from the metal microneedle array, and trim the excessively high center column in the PDMS mold to 3.0mm (even if the center column is about 3mm higher than the mold level);

7. Melting material: spread polystyrene powder (Polystyrene, PS) in the concave area in the center of the mold under the premise of keeping the center column vertical, clamp the upper and lower sides of the mold with two flat weights, and then Put it in a muffle furnace at 200~230°C for 35~50min;

8. Cooling and solidification: Take out the whole body, place it flat on a horizontal surface and cool for 0.5~1min, remove the heavy objects, separate PS and PDMS, if the corresponding position of the needle on the back of the PS microneedle array is covered with PS film, carefully remove it;

9. Adhesive cavity: Make a concave elastic PDMS mixture cavity and adhere it to the back of the PS microneedle array.

Example 2 Peripheral (micro) blood collection patch

The production steps are the same as in Example 1, the difference is:

Step 6 Trim the central column to make it about 1mm lower than the highest level;

The PS microneedle array obtained after separating the PS and PDMS mixture in step 8 is the desired blood collection patch.

Finally, as shown in Figure 2.

Embodiment 3 Electroosmotic blood collection/transdermal drug delivery patch

The production steps are the same as in Example 1, the difference is:

Select materials that can generate surface charges in body fluids, such as polyamine, polyamide, polyphenylene ether, etc. In this embodiment, high-hardness polyamine is used to replace polystyrene;

Step 9 Adhere the cavities with flexible electrodes.

Claims (5)

1. the preparation method of an adhesive type empty micropin array, it is characterized in that, described adhesive type empty micropin array comprises a flat board, flat board is provided with the empty micropin of a group pattern, the length of empty micropin is 0.1 ~ 3mm, described flat board is provided with cavity, and described cavity and the cavity connects of microneedles comprise the following steps:

S1. depletion belongs to empty micropin array, with lubricator lubricates microneedles array;

S2. by weight A and the B component of 1:10=A:B mixing polydimethylsiloxane, stir, preheating, obtains mixture;

S3. the microneedles array of S1 gained is slowly inserted in the mixed liquor of S2 gained, fixing, evacuation, solidification, the demoulding, obtains polydimethylsiloxane mould;

S4., under the vertical condition keeping newel, Polystyrene powder is spread in the sunk area of mould central authorities, with two pieces of flat boards by teamed for mould upper and lower surface, then 35 ~ 50min in the Muffle furnace being placed on 200 ~ 230 DEG C;

S5. cooling curing, obtains polystyrene micro-nano needle head array;

S6. preparation has the elasticity polydimethylsiloxane cavity of spill, is adhered to the polystyrene micro-nano needle head array back side, obtains adhesive type empty micropin array.

2. preparation method according to claim 1, is characterized in that, the preheating described in step S2 be in the baking oven being positioned over 70 DEG C 6.5 ~ 7.5min or be positioned over 80 DEG C baking oven in 1.5 ~ 2min.

3. preparation method according to claim 1, is characterized in that, the microneedles array described in step S3 slowly inserts mixed liquor 2 ~ 3mm, and being cured as described in step S3 is positioned over 8 ~ 12min in the baking oven of 70 DEG C or is positioned over 4 ~ 6min in the baking oven of 80 DEG C.

4. preparation method according to claim 1, is characterized in that, the length of the newel of step S3 gained polydimethylsiloxane mould is 0.1 ~ 3mm.

5. preparation method according to claim 1, is characterized in that, the polydimethylsiloxane mould of step S3 gained can be recycled.