阅读说明：本技术 一种三维堆叠式多功能瞬态医疗芯片 (Three-dimensional stacked multifunctional transient medical chip ) 是由 陈珉 于欣格 于 2020-05-19 设计创作，主要内容包括：本发明公开了一种三维堆叠式多功能瞬态医疗芯片,属于新型微电子材料与器件、生物可降解电子器件以及医疗电子器件技术领域。该方法医疗芯片构筑一种三维堆叠式多功能瞬态医疗芯片,该多功能医疗芯片的特点主要包括：1)由两层或两层以上的器件堆叠而成；2)不同对叠层的器件拥有相同或者不同的医疗功能；3)制备器件所需要的材料全部由生物可降解电子材料组成；4)不同器件层之间由不同生物可降解绝缘材料进行封装。本发明能够加快新型医疗电子器件的快速发展,特别是对于提高瞬态医疗电子器件的多功能集成、降低病患医疗成本等方面具有深远的意义。(The invention discloses a three-dimensional stacked multifunctional transient medical chip, and belongs to the technical field of novel microelectronic materials and devices, biodegradable electronic devices and medical electronic devices. The medical chip of the method constructs a three-dimensional stacked multifunctional transient medical chip, and the multifunctional medical chip is characterized by mainly comprising the following steps: 1) is formed by stacking two or more layers of devices; 2) different pairs of stacked devices have the same or different medical functions; 3) the materials required for preparing the device are all made of biodegradable electronic materials; 4) different biodegradable insulating materials are used for packaging different device layers. The invention can accelerate the rapid development of novel medical electronic devices, and has profound significance in the aspects of improving the multifunctional integration of transient medical electronic devices, reducing the medical cost of patients and the like.)

1. A three-dimensional stacked multifunctional transient medical chip, comprising at least: the device comprises a substrate, a functional device layer and an encapsulation layer;

1) providing a biocompatible, biodegradable material as a substrate, the biocompatible/degradable substrate having flexible characteristics;

2) constructing a first functional device layer on the biocompatible/degradable substrate, wherein the materials required by the functional device layer are all biocompatible and biodegradable materials;

3) encapsulating the functional device layer, wherein materials required by the encapsulating layer are all biocompatible and biodegradable materials;

4) the functional device layer and the encapsulation layer are repeatedly stacked one or more times, wherein different device layers have the same or different medical functions.

2. The three-dimensional stacked multifunctional transient medical chip of claim 1, wherein: the biocompatible and degradable substrate material mainly comprises fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (ricepaper), Polycaprolactone (PCL) and polyglycolic acid (PGA).

3. The three-dimensional stacked multifunctional transient medical chip of claim 1, wherein: the preparation method of the biocompatible and degradable substrate comprises a spin coating method or a titration method, and the thickness of the finally obtained substrate is 1-500 mu m.

4. The three-dimensional stacked multifunctional transient medical chip of claim 1, wherein: the functional device layer comprises an active device, a passive device and a functional electronic circuit consisting of the active device and the passive device.

5. The three-dimensional stacked multifunctional transient medical chip according to claim 4, wherein: the metal materials required by the functional device layer comprise Zn, Mg, Fe, W and Mo.

6. The three-dimensional stacked multifunctional transient medical chip according to claim 4, wherein:the dielectric material comprises SiO₂、Si₃N₄MgO, degradable polymer.

7. The three-dimensional stacked multifunctional transient medical chip according to claim 4, wherein: the semiconductor material comprises Si, Ge, SiGe, ZnO.

8. The three-dimensional stacked multifunctional transient medical chip according to claim 4, wherein: the biodegradable electronic device layer comprises single elements such as transistors, memristors, diodes, resistors, inductors, capacitors and the like, or an integrated system formed by the elements.

9. The three-dimensional stacked multifunctional transient medical chip of claim 1, wherein: the packaging layer comprises inorganic SiO₂、Si₃N₄MgO, or organic fibroin, lactic-co-glycolic acid (PLGA), rice paper (ricepaper), Polycaprolactone (PCL), polyglycolic acid (PGA).

Technical Field

The invention discloses a three-dimensional stacked multifunctional transient medical chip, and belongs to the technical field of novel microelectronic materials and devices, biodegradable electronic devices and medical electronic devices.

Background

Transient medical electronics have been proposed to the present (Science,2012,337,1640.) since 2012, and have been widely noticed and developed due to a series of advantages of biocompatibility, biodegradability, no environmental pollution, etc. Particularly with respect to implantable electronic devices, transient medical electronic devices can degrade themselves within a living body after they have completed treatment or monitoring of the living body, without the need for a second surgical procedure to remove them. The presentation and the application of the transient medical electronic device can greatly reduce the operation pain and the operation risk of patients and simultaneously reduce the medical cost. The key to realizing the transient medical electronic device is that the materials needed from the substrate, the device to the packaging layer have the characteristics of biocompatibility and biodegradability at the same time. However, the lifetime of the conventional transient medical electronic device in a living body is determined by the degradation rate of the encapsulation layer, and has the disadvantages of single function, low integration level, and the like. For example, implantable transient hyperthermia devices with infection reduction or elimination are not known for their efficacy in the affected area when they are completely degraded in vivo.

Three-dimensional integration of the treatment device with the monitoring device is an effective way. For example, the treatment device is located on the upper layer, the monitoring device is located right below the treatment device, the two layers of devices are isolated by the packaging layer, and the upper part of the treatment device layer is packaged. When the treatment device is fully degraded, the monitoring device below the treatment device can carry out in-situ monitoring on the curative effect of the treatment device. By monitoring the feedback of data, the lifetime of the therapeutic device within the living body is optimized, i.e. the uppermost encapsulation layer is optimized. Thus, when the treatment device is completely degraded, the diseased region is completely recovered as usual, and the recovery condition can be analyzed in situ by the monitoring device below. The invention further promotes the development of the transient medical electronic device, and has important significance for greatly expanding the medical and practical application of the transient medical electronic device. In view of this, it becomes necessary to construct a three-dimensional stacked multifunctional transient medical chip.

Disclosure of Invention

According to the technical background, the invention aims to construct a three-dimensional stacked multifunctional transient medical chip, and the medical chip with multifunctional integration, transient and three-dimensional stacking is finally formed by longitudinally stacking device layers with the same or different functions in three positions and using an insulating medium as a package between the device layers. The three-dimensional stacked multifunctional transient medical chip provided by the invention has important significance for promoting the rapid development of the transient medical electronic device and expanding the medical and practical application of the transient medical electronic device.

To achieve the above and other related objects, the present invention provides a three-dimensional stacked multifunctional transient medical chip, which at least comprises: the device comprises a substrate, a functional device layer and an encapsulation layer;

1) providing a biocompatible, biodegradable material as a substrate, the biocompatible/degradable substrate having flexible characteristics;

2) constructing a first functional device layer on the biocompatible/degradable substrate, wherein the materials required by the functional device layer are all biocompatible and biodegradable materials;

3) encapsulating the functional device layer, wherein materials required by the encapsulating layer are all biocompatible and biodegradable materials;

4) the functional device layer and the encapsulation layer are repeatedly stacked one or more times, wherein different device layers have the same or different medical functions.

Optionally, the biocompatible and degradable substrate material mainly includes, but is not limited to, fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like.

Optionally, the metal material required by the functional device layer includes Zn, Mg, Fe, W, Mo, the dielectric material is SiO2, Si3N4, MgO, degradable polymer, and the semiconductor material is Si, Ge, SiGe, ZnO, but is not limited to the above.

Optionally, the biodegradable electronic device layer includes a single element such as a transistor, a memristor, a diode, a resistor, an inductor, a capacitor, or an integrated system composed of the above elements.

Optionally, the encapsulation layer comprises inorganic SiO₂、Si₃N₄MgO, or organic fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like, but are not limited thereto.

Another objective of the present invention is to provide a process for preparing a three-dimensional stacked multifunctional transient medical chip, which at least comprises the following steps:

1) coating a biodegradable substrate precursor on a temporary substrate by a spin coating method or a titration method;

2) constructing a monitoring device layer on the biodegradable substrate for in-situ monitoring of the therapeutic effect of the therapeutic device;

3) constructing a first packaging layer on the monitoring device layer;

4) constructing a therapeutic device on the first encapsulation layer for accelerating healing of the infected wound;

5) constructing a second encapsulation layer on the therapeutic device for preventing the tissue fluid from rapidly degrading the therapeutic device;

6) stripping the constructed stacked multifunctional transient medical chip from the temporary substrate;

7) and tightly attaching the constructed flexible stacked multifunctional transient medical chip to the diseased organ.

As described above, the present invention provides a three-dimensional stacked multifunctional transient medical chip. The invention has the following advantages and prominent technical effects: 1) different from the traditional medical electronic device with single medical function, the multifunctional transient medical chip provided by the invention integrates the specific functions of different device layers on the same chip, thereby greatly increasing the integration level of the chip; 2) the specific medical functions among different device layers on the multifunctional transient medical chip have the characteristic of mutual synergistic action, so that the working efficiency of a single chip is improved; 3) the multifunctional transient medical chip provided by the invention can be used for carrying out in-situ monitoring on the curative effect of each device layer, and has important guiding significance for analyzing the illness state of a patient, the curative effect of a medical device and the like; 4) the multifunctional transient medical chip provided by the invention is completely composed of biocompatible and biodegradable materials, can be automatically degraded without secondary operation after being placed into a living body, greatly relieves the pain of patients, and reduces the operation risk and medical cost.

Drawings

Fig. 1 shows a method for preparing a biodegradable, biocompatible substrate in a three-dimensional stacked multifunctional transient medical chip according to the present invention.

Fig. 2 shows the preparation of a monitoring device and a packaging layer 1 in a three-dimensional stacked multifunctional transient medical chip according to the present invention.

Fig. 3 shows the preparation of the therapeutic device and the packaging layer 2 in the three-dimensional stacked multifunctional transient medical chip of the invention.

Fig. 4 shows the multifunctional transient medical chip being peeled off from the temporary substrate in a three-dimensional stacked multifunctional transient medical chip according to the present invention.

Fig. 5 shows a three-dimensional stacked multifunctional transient medical chip according to the present invention, in which the multifunctional transient medical chip is closely attached to a diseased organ.

Figure 6 shows a combination of functional layers and encapsulation layers according to the present invention.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

It should be noted that the present embodiment provides only one specific step for preparing the multifunctional transient medical chip to illustrate the basic concept of the present invention, and only the relevant contents related to the present embodiment are shown in the step. In practical implementation of the present invention, the function of the device layer with required function and the number of stacked layers can be changed as required to realize the required medical function, and the material and thickness of the encapsulation layer can be changed to control the degradation rate of the functional device layer, and the layout of the components may be more complicated.

As shown in fig. 1-6, a three-dimensional stacked multifunctional transient medical chip at least comprises: the device comprises a substrate, a functional device layer and an encapsulation layer;

1) providing a biocompatible, biodegradable material as a substrate, the biocompatible/degradable substrate having flexible characteristics; 2) constructing a first functional device layer on the biocompatible/degradable substrate, wherein the materials required by the functional device layer are all biocompatible and biodegradable materials; 3) encapsulating the functional device layer, wherein materials required by the encapsulating layer are all biocompatible and biodegradable materials; 4) the functional device layer and the encapsulation layer are repeatedly stacked one or more times, wherein different device layers have the same or different medical functions.

Optionally, the biocompatible and degradable substrate material mainly comprises fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), and polyglycolic acid (PGA).

Optionally, the preparation method of the biocompatible and degradable substrate comprises a spin coating method or a titration method, and the thickness of the finally obtained substrate is 1-500 m.

Optionally, the functional device layer includes an active device, a passive device, and a functional electronic circuit composed of the active device and the passive device.

Optionally, the metal material required by the functional device layer includes Zn, Mg, Fe, W, Mo; the dielectric material comprises SiO2, Si3N4, MgO and degradable polymer; the semiconductor material comprises Si, Ge, SiGe, ZnO.

Optionally, the biodegradable electronic device layer includes a single element such as a transistor, a memristor, a diode, a resistor, an inductor, and a capacitor, or an integrated system composed of the above elements.

Optionally, the encapsulation layer includes inorganic SiO2, Si3N4, MgO, or organic fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like.

The process flow diagram of the method of the invention comprises the following steps:

1) as shown in fig. one, the biodegradable substrate precursor is coated on the temporary substrate by spin coating or titration, in this particular case, the biodegradable substrate is PLGA obtained by titration, and the temporary substrate is a silicon wafer;

2) as shown in fig. two, a monitoring device layer is constructed on the biodegradable substrate for in-situ monitoring of the therapeutic effect of the therapeutic device, in this particular case, the monitoring device used is a silicon-based virus sensor;

3) as shown in fig. two, an encapsulation layer 1 is constructed on the monitoring device layer, in this specific example, the used encapsulation layer 1 is a PLGA thin film obtained by a spin coating method;

4) as shown in fig. three, a therapeutic device is constructed on the packaging layer 1 for accelerating the healing of an infected wound, in this particular case, the constructed therapeutic device is a Mg-based thermotherapy device;

5) as shown in fig. three, an encapsulation layer 2 is constructed on the therapeutic device for preventing the tissue fluid from rapidly degrading the therapeutic device, in this specific example, the encapsulation layer 2 is constructed to be a silicon oxide/silicon nitride multilayer structure, so that the service life of the therapeutic device is longer than the expected healing time of the infected wound;

6) as shown in fig. four, the constructed stacked multifunctional transient medical chip is peeled off from the temporary substrate;

7) as shown in fig. five, the constructed flexible stacked multifunctional transient medical chip is closely attached to a diseased device, and attention is paid to: in practice, the organs of the living body should be curved surfaces, and for the sake of simplicity, the schematic diagram is replaced by a plane;

8) after the packaging layer 2 and the therapeutic device are completely degraded by tissue fluid in a living body, detecting the vital signs of the original diseased organ by using the silicon-based virus sensor, thereby monitoring the curative effect of the therapeutic device; when the monitoring work is finished, the tissue fluid can be degraded; thus, the preparation, work and degradation of the multifunctional transient medical chip are completed.

It should be noted that, for convenience in this embodiment, the biodegradable multifunctional transient medical chip takes the Mg-based hyperthermia device as a therapeutic device and the silicon-based virus sensor as a monitoring device to illustrate the idea of the present invention and the preparation method of the material and the device, but the three-dimensional stacked multifunctional transient medical chip with other functions is also within the protection scope of the present invention.

In summary, the three-dimensional stacked multifunctional transient medical chip provided by the present invention relates to the construction of two or more functional device layers, and the multifunctional medical chip is characterized by mainly comprising: 1) is formed by stacking two or more layers of devices; 2) different pairs of stacked devices have the same or different medical functions; 3) the materials required for preparing the device are all made of biodegradable electronic materials; 4) different biodegradable insulating materials are used for packaging different device layers. The invention can accelerate the rapid development of novel medical electronic devices, and has profound significance in the aspects of improving the multifunctional integration of transient medical electronic devices, reducing the medical cost of patients and the like.

The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.