CN113975619B - Device and method for controlling microneedle penetration based on light - Google Patents
Device and method for controlling microneedle penetration based on light Download PDFInfo
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- CN113975619B CN113975619B CN202111330028.8A CN202111330028A CN113975619B CN 113975619 B CN113975619 B CN 113975619B CN 202111330028 A CN202111330028 A CN 202111330028A CN 113975619 B CN113975619 B CN 113975619B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0061—Methods for using microneedles
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Abstract
The invention discloses a device and a method for controlling microneedle penetration based on light. The device comprises: the light response shape memory composite material comprises a photo-thermal conversion material and a temperature response shape memory material; heating and stretching the photoresponse shape memory composite material to a set length, then cooling the photoresponse shape memory composite material to maintain the stretched temporary shape, fixing two ends of the photoresponse shape memory composite material on a fixed seat, wherein the middle part of the photoresponse shape memory composite material is upwards convex, and the lower surface of the middle part of the photoresponse shape memory composite material is fixedly provided with downwards-facing micro needles; and the light source can irradiate the light to respond to the shape memory composite material, so that the shape memory composite material shrinks and returns to the original shape after absorbing heat and increasing temperature, and then the micro-needle is driven to move downwards. The method adopts the device, the light source is irradiated on the photoresponse shape memory composite material, and the microneedle is driven to move downwards to pierce into the target object in the process that the photoresponse shape memory composite material absorbs heat and rises temperature under illumination and then contracts and returns to the original shape.
Description
Technical Field
The invention relates to the technical field of microneedle application, in particular to a device and a method for controlling microneedle penetration based on light.
Background
The microneedle transdermal drug delivery platform is a novel transdermal drug delivery system which is rapidly developed in the last thirty years, and has the advantages of no pain, minimal invasion, self-service use and the like.
The micro-needle forms a large number of micron-sized channels on the surface of the target tissue in a physical mode, so that the delivery efficiency of the drug is greatly improved, and the drug is particularly used for delivering biomacromolecules such as vaccines, insulin, antibodies, genetic substances and the like.
The most important action mode of the current micro-needles is to press the micro-needles by using fingers, and although the mode brings convenience to the use of the micro-needles, the imbalance and instability of the acting force affect the consistency of the micro-needles on drug delivery.
Meanwhile, under the influence of rapid development of the microneedle in the field of transdermal drug delivery, a great deal of research in recent years expands the application range of microneedle drug delivery to other tissues and organs, such as cornea, gastrointestinal tract, vascular tissue, heart and the like. The application of the micro-needle to the tissues and organs puts higher requirements on the precise control of the micro-needle penetration process (such as penetration depth, acting force, triggering mode and the like).
Therefore, development of more versatile, accurate, effective, and on-demand microneedle action is urgently needed.
A variety of microneedle application devices and methods have been developed to improve the precise effectiveness of microneedles for drug delivery. The most common approach is to use a spring or other elastic element to achieve repeatability of microneedle penetration by releasing the fixed energy.
In addition, patent CN105126243B discloses a microneedle propulsion device based on high-pressure gas, which generates impact force through air pressure release, so that the needle body structure completely enters the skin to achieve the stability of dosage.
Patent CN105246541B discloses a microneedle applicator based on a structural design, which is transformed from a first stable configuration to a second stable configuration by applying force, utilizing the fixed energy difference of two different stable configurations to improve the stability of the application.
While these devices and methods improve the repeatability of microneedle application, they are generally limited to a fixed force or penetration depth, and there is some gap in precise control of distance. Meanwhile, the existing triggering mode cannot realize the puncture of the microneedle in a remote control manner.
Disclosure of Invention
The invention provides a device for controlling microneedle penetration based on light, which can remotely control microneedle penetration through illumination, in particular to a device which can drive the microneedle penetration by enabling a light source to act on a light response shape memory composite material to generate a shape memory effect, and can accurately control the force applied on the microneedle and limit the maximum penetration depth of the microneedle by regulating and controlling the deformation degree of the light response shape memory composite material.
A light-based control microneedle penetration device comprising:
the light response shape memory composite material comprises a photo-thermal conversion material and a temperature response shape memory material; heating and stretching the photoresponse shape memory composite material to a set length, then cooling the photoresponse shape memory composite material to maintain the stretched temporary shape, fixing two ends of the photoresponse shape memory composite material on a fixed seat, wherein the middle part of the photoresponse shape memory composite material is raised upwards, and the lower surface of the middle part of the photoresponse shape memory composite material is fixedly provided with downwards micro-needles;
the light source can irradiate the light response shape memory composite material to ensure that the composite material shrinks to return to the original shape after absorbing heat and increasing temperature, thereby driving the micro-needle to move downwards.
When the device for controlling the puncture of the micro-needle based on light works, when a light source irradiates on the light response shape memory composite material in a temporary state, the light response shape memory composite material partially fixed on the fixed seat generates controllable deformation recovery according to the illumination intensity, so that force is generated to drive the micro-needle to be punctured accurately.
The photothermal conversion material can be compounded on the shape memory material in a coating, mixing or depositing mode and the like, and the deformation state of the shape memory material is influenced by converting light energy into heat energy.
The device for controlling the puncture of the microneedle based on light can be at least one of a solid microneedle, a dissolvable microneedle, a hollow microneedle, a coated microneedle and a hydrogel microneedle.
The shape memory material of the light-controlling microneedle penetration-based device may be at least one of a shape memory polymer, a shape memory ceramic, and a shape memory alloy.
The shape memory polymer includes but is not limited to at least one of polynorbornene, crosslinked polyethylene, trans 1,4-polyisoprene, perfluorosulfonic acid/polytetrafluoroethylene copolymer, ethylene/vinyl acetate copolymer, and styrene/butadiene copolymer.
The shape memory ceramic includes, but is not limited to, at least one of zirconia, alumina, silicon carbide, and silicon nitride.
The shape memory alloy includes, but is not limited to, at least one of nickel-titanium alloy, gold-cadmium alloy, copper-zinc alloy, nickel-aluminum alloy, and silver-cadmium alloy.
The photo-thermal conversion material can be at least one of carbon nano tubes, graphene, polydopamine, prussian blue, copper sulfide and gold nano particles.
In the device for controlling microneedle penetration based on light, the wavelength of the light source is preferably 265nm to 1000 μm, and more preferably 780nm to 3 μm. The preferred wavelength range is more advantageous in photothermal conversion, and has higher utilization efficiency, and light energy is more easily converted into heat energy.
As a general inventive concept, the invention also provides a method for puncturing the micro-needle based on light control, which comprises the steps of irradiating a light source on the light response shape memory composite material by using the device for puncturing the micro-needle based on light control, and driving the micro-needle to move downwards to puncture a target object in the process that the light response shape memory composite material shrinks and returns to the original shape after absorbing heat and increasing temperature under the irradiation of light.
Compared with the prior art, the invention has the main advantages that:
1) The device and the method for controlling the puncture of the micro-needle based on light can realize the remote control puncture of the micro-needle by controlling the deformation and the recovery of the light response shape memory composite material with the temporary shape after stretching.
2) The device and the method for controlling the puncture of the microneedles can adjust and control the deformation recovery state of the light response shape memory material by changing the light intensity, thereby realizing the control of the force applied to the microneedles according to the requirements.
3) The device and the method for controlling the penetration of the micro-needle based on light can control the deformation recovery amount of the light response shape memory material by changing the pre-stretching strain of the light response shape memory material, thereby limiting the maximum penetration depth of the micro-needle.
Drawings
Fig. 1 is a schematic structural view of a light-controlled microneedle penetration-based device according to an embodiment of the present invention, in which: 1 represents a photoresponse shape memory composite material, 2 represents a fixed seat, 3 represents a micro needle, 4 represents an adhesive layer, 5 represents a light source, and 6 represents a punctured object;
FIG. 2 is a graph of light intensity versus temperature for an optically responsive shape memory composite in accordance with an embodiment of the present invention;
FIG. 3 is a graph of light intensity versus pressure for a light responsive shape memory composite in accordance with an embodiment of the present invention;
fig. 4 is a schematic and pictorial representation of a light-controlled microneedle penetration-based device of an embodiment of the present invention at different pre-tension deformations.
Detailed Description
The invention is further described with reference to the following drawings and specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The following examples are conducted under conditions not specified, usually in accordance with conventional conditions or conditions recommended by the manufacturer.
Referring to fig. 1, an embodiment of the present invention provides a device for controlling microneedle penetration based on light, which includes a light-responsive shape memory composite material 1, a fixing base 2, microneedles 3, an adhesive layer 4, and a light source 5, and the acting object of the device is a penetrated object 6.
The photoresponsive shape memory composite material 1 may be in the form of a strip, a square or a circle. In the present embodiment, the photo-responsive shape-memory composite material 1 is in a long strip shape, and is cooled to fix its temporary shape by being stretched to 1 to 2 times the length of the original shape at 100 ℃. The length of the utility model can be cut according to the requirement when in use.
The two ends of the light response shape memory composite material 1 are fixed on the fixed seat 2. The microneedles 3 and the photo-responsive shape memory composite 1 are connected by an adhesive layer 4. The light source 5 is used for triggering the light response shape memory composite material 1 to deform and recover, so that force is provided for driving the micro-needle 3 to puncture.
The photo-responsive shape memory composite material 1 includes a photo-thermal conversion material and a temperature-responsive shape memory material. The shape memory material may be at least one of a shape memory alloy, a shape memory polymer, a shape memory ceramic. The shape memory material is capable of changing shape, position or strain in response to a change in temperature. In this embodiment, the shape memory material is a shape memory polymer, and may be selected from one of polynorbornene, cross-linked polyethylene, trans 1,4-polyisoprene, perfluorosulfonic acid/polytetrafluoroethylene copolymer, ethylene/vinyl acetate copolymer, and styrene/butadiene copolymer. The photothermal conversion material can be selected from one of carbon nano tubes, graphene, polydopamine, prussian blue, copper sulfide and gold nano particles. The photothermal conversion material can be coated, mixed or deposited on the shape memory material, and the deformation state of the shape memory polymer is influenced by converting light energy into heat energy. As shown in fig. 2, the photoresponsive shape-memory composite material 1 of the present embodiment adopts perfluorosulfonic acid/polytetrafluoroethylene copolymer as a shape-memory polymer, and utilizes polydopamine as a photothermal conversion material, so as to generate different temperatures according to the change of light intensity.
The holders 2 are used to fix both ends of the photo-responsive shape memory material 1, and force is applied to the microneedles 3 by restricting the direction of deformation recovery.
The microneedles 3 may be one of solid microneedles, dissolvable microneedles, hollow microneedles, coated microneedles, and hydrogel microneedles. In the present embodiment, the microneedle 3 is a solid microneedle, and the material may be selected from one of copper, polylactic acid, polycaprolactone, and silicon.
The adhesive layer 4 is an acrylate pressure sensitive adhesive, and the micro-needle 3 is adhered to the middle part of the photoresponse shape memory composite material 1.
The wavelength of the light source 5 is 780nm to 3 μm. In this embodiment, the wavelength used by the light source 5 is 808nm.
When the device based on light control microneedle penetration works, when the light source 5 irradiates on the light response shape memory composite material 1 in a temporary state, the light response shape memory composite material 1 partially fixed on the fixing seat 2 generates controllable deformation recovery according to the illumination intensity, so that force is generated to drive the microneedle to penetrate accurately.
Specifically, the light source 5 is irradiated on the photoresponse shape memory composite material 1, and the microneedle 3 is driven to move downwards to penetrate into the target object in the process that the photoresponse shape memory composite material 1 absorbs heat under illumination, is heated and then contracts to return to the original shape.
The photoresponsive shape memory composite material 1 can generate different temperatures according to the change of light intensity, so that the deformation recovery state of the photoresponsive shape memory composite material 1 can be controlled through the light intensity. Meanwhile, the two ends of the fixing seat 2 are fixed to limit the deformation recovery direction, so that the force applied to the microneedles 3 can be regulated and controlled. In this embodiment, the photoresponsive shape-memory composite material 1 has a length of 2cm, a width of 3mm, a fixed end distance of 9mm, a middle height of 4mm, and a pre-stretching deformation of 1.4 times the initial length. The relationship between the light intensity and the applied force is shown in fig. 3.
The final recovery length of the light response shape memory composite material 1 is influenced by the pre-stretching deformation rate, and the higher the pre-stretching deformation rate is, the larger the recovery amount is for the material with the same length. The maximum penetration depth can thus be limited by controlling the pre-stretching deformation of the light responsive shape memory composite 1. In this embodiment, the photoresponsive shape-memory composite material 1 has a length of 2cm, a width of 3mm, a fixed end distance of 9mm and a middle height of 4mm. When the pre-stretching deformation is respectively 1.2 times, 1.4 times and 1.6 times, the pre-stretching deformation is at 14.3mW/mm 2 The penetration is shown in fig. 4 under the light intensity of (c).
It can be seen that the device and method for light-controlling microneedle penetration based on light according to the present invention have the following beneficial effects:
1) The shape memory composite material can be responded by light to deform and recover, so that the micro-needle can be remotely controlled to puncture.
2) The deformation recovery state of the photoresponse shape memory material can be adjusted and controlled by changing the light intensity, so that the control on the application of force to the micro-needle as required is realized.
3) The deformation recovery amount of the light-responsive shape memory material can be controlled by changing the pre-stretching strain of the light-responsive shape memory material, so that the maximum penetration depth of the micro-needle is limited.
Furthermore, it should be understood that various changes and modifications can be made by one skilled in the art after reading the above description of the present invention, and equivalents also fall within the scope of the invention as defined by the appended claims.
Claims (9)
1. A light-based control microneedle penetration device, comprising:
the light response shape memory composite material (1) comprises a photo-thermal conversion material and a temperature response shape memory material; the photoresponse shape memory composite material (1) is heated, stretched to a set length and then cooled to maintain the stretched temporary shape, then two ends of the photoresponse shape memory composite material are fixed on a fixed seat (2), the middle part of the photoresponse shape memory composite material is upwards convex, and the lower surface of the middle part of the photoresponse shape memory composite material is fixedly provided with downwards-facing micro-needles (3);
the light source (5) can irradiate light to respond to the shape memory composite material (1) so that the shape memory composite material shrinks and returns to the original shape after absorbing heat and increasing temperature, and then the micro-needle (3) is driven to move downwards;
according to the device for controlling the puncturing of the micro-needle based on light, when the light source (5) irradiates the light response shape memory composite material (1), the light response shape memory composite material (1) can drive the micro-needle (3) to move downwards to puncture a target object in the process of shrinking and returning to the original shape after absorbing heat and raising temperature under illumination.
2. The device according to claim 1, wherein the microneedle (3) is at least one of a solid microneedle, a dissolvable microneedle, a hollow microneedle, a coated microneedle, a hydrogel microneedle.
3. The device of claim 1, wherein the shape memory material is at least one of a shape memory polymer, a shape memory ceramic, a shape memory alloy.
4. The device of claim 3, wherein the shape memory polymer comprises at least one of polynorbornene, cross-linked polyethylene, trans 1,4-polyisoprene, perfluorosulfonic acid/polytetrafluoroethylene copolymer, ethylene/vinyl acetate copolymer, styrene/butadiene copolymer.
5. The device of claim 3, wherein the shape memory ceramic comprises at least one of zirconia, alumina, silicon carbide, silicon nitride.
6. The device of claim 3, wherein the shape memory alloy comprises at least one of a nickel titanium alloy, a gold cadmium alloy, a copper zinc alloy, a nickel aluminum alloy, and a silver cadmium alloy.
7. The device of claim 1, wherein the photothermal conversion material is at least one of carbon nanotubes, graphene, polydopamine, prussian blue, copper sulfide, gold nanoparticles.
8. The device according to claim 1 or 7, characterized in that the wavelength of the light source (5) is 265nm to 1000 μm.
9. The device according to claim 8, characterized in that the wavelength of the light source (5) is 780nm to 3 μm.
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| CN109718394A (en) * | 2019-02-22 | 2019-05-07 | 华南农业大学 | Nano combined biological support in the multiple dimensioned hole of a kind of driving shape memory of photo-thermal and preparation method thereof |
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| US7655001B2 (en) * | 2001-03-23 | 2010-02-02 | Petrakis Dennis N | Temperature responsive systems |
| US6591124B2 (en) * | 2001-05-11 | 2003-07-08 | The Procter & Gamble Company | Portable interstitial fluid monitoring system |
| WO2007143623A2 (en) * | 2006-06-02 | 2007-12-13 | Stalford Harold L | Methods and systems for micro machines |
| US20120130207A1 (en) * | 2009-04-29 | 2012-05-24 | Janisys Limited | micro-needle device and apparatus and a method for applying a micro-needle element to a site on the skin of a subject |
| US20110224515A1 (en) * | 2009-09-08 | 2011-09-15 | SensiVida Medical Technologies, Inc. | Replaceable microneedle cartridge for biomedical monitoring |
| CA2827158A1 (en) * | 2011-01-18 | 2012-07-26 | Massachusetts Institute Of Technology | Device and uses thereof |
| CN103157178B (en) * | 2013-02-05 | 2014-12-31 | 北京化工大学 | Seal type tool capable of accurately controlling microneedle insertion length |
| CN107349518B (en) * | 2017-06-22 | 2020-10-02 | 浙江理工大学 | Near-infrared light sensitive microneedle patch and preparation method thereof |
| EP3723610A1 (en) * | 2017-12-15 | 2020-10-21 | Koninklijke Philips N.V. | Wearable or insertable devices with microneedles that include mechanically-responsive material |
| CN108730141B (en) * | 2018-04-08 | 2020-01-17 | 中国地质大学（武汉） | Laser remote photo-thermal driving device |
| CN108757357B (en) * | 2018-04-25 | 2019-12-17 | 中国地质大学（武汉） | Laser-induced liquid metal cooperated shape memory alloy driving device |
| EP3838261A1 (en) * | 2019-12-20 | 2021-06-23 | Ares Trading S.A. | Microneedle array, actuator and method of use |
| CN112853758B (en) * | 2021-03-08 | 2022-08-26 | 广东工业大学 | Shape memory driver with rapid photo-thermal response and preparation method and application thereof |
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| CN109718394A (en) * | 2019-02-22 | 2019-05-07 | 华南农业大学 | Nano combined biological support in the multiple dimensioned hole of a kind of driving shape memory of photo-thermal and preparation method thereof |
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