CN115704772B - Microelectronic integrated device and molecular information detection method - Google Patents

Abstract

The application discloses microelectronic integrated equipment and a molecular information detection method. The microelectronic integrated device includes: a molecular channel for transmitting body fluid molecules carrying biological information; the molecular sensor is used for detecting the concentration of body fluid molecules transmitted by the molecular channel to obtain an optical signal representing the concentration; the photoelectric detector is connected with the molecular sensor and used for converting the optical signal into an electric signal; the wireless communication unit is connected with the photoelectric detector and is used for wirelessly transmitting out an electric signal; the molecular channel is provided with a plurality of magnetic control micron elements with micron-sized dimensions, and the magnetic control micron elements are used for accelerating the propagation speed of body fluid molecules in the molecular channel. The liquid-body molecule can be rapidly identified by the molecule sensor, and the molecule information is transmitted to the external receiving equipment through the wireless communication unit, so that the fusion of the molecule communication and the wireless communication is realized, the transmission delay is small, and the requirements of rapid identification and real-time transmission of the molecule information in the micro-area environment are met.

Description

Microelectronic integrated device and molecular information detection method

Technical Field

The present application relates to the field of molecular communication, and in particular to a microelectronic integrated device and a molecular information detection method.

Background Art

As one of the future 6G application scenarios, the Internet of bio-nanothings (IoBNT) depicts the future network coverage towards more microscopic areas, realizing real-time interaction between biological cells and the network. As one of the components of the 6G body area network, devices of different sizes and different communication principles inside and outside the body will be interconnected, and all human information including cell status will be transmitted in real time through wireless networks. At the same time, the micro-machines in the IoBNT can be remotely controlled through the 6G network to achieve precise targeted treatment and micro-surgery, which is of great significance to human health monitoring and disease prevention.

Since traditional electromagnetic wave communication systems cannot be further miniaturized to micro-nano sizes, and information transmission between biological cells is carried by molecules, it is necessary to build molecular communication devices that can release, transmit and identify specific molecular information at the micro-nano scale. At the same time, some biomarkers in body fluids, such as nucleic acid molecules, protein molecules, blood sugar, etc., are characteristic indicators of some diseases, viruses and bacterial infections. How to identify and decode this information and transmit it to in vitro devices in real time through wireless networks is of great practical significance.

Here, tumor cells or viruses are the transmitters in the natural molecular communication system. They release specific protein molecules and nucleic acid molecules into body fluids. These information molecules are propagated to various tissues and organs through the body fluid circulation. When they diffuse to the corresponding molecular sensor (receiver), they will be specifically identified. Since such an identification process needs to be easy to read, some identification molecules and nanostructures are usually introduced in the design of molecular receivers to induce some optical, electrical, and magnetic effects. These optical, electrical, and magnetic changes are detected by related detection devices, and after processing, they are sent to the receiving device outside the body by the antenna through traditional electromagnetic wave communication, thus completing the identification and wireless transmission of molecular information.

However, there is a big problem in practical applications: the transmission time of molecular information is long (end-to-end). This is because in molecular communication systems, information molecules propagate in molecular channels in a free diffusion manner, with a low diffusion coefficient, weak diffusion driving force, and long diffusion distance, which seriously affects the real-time performance of molecular information during transmission, especially in some scenarios that are sensitive to time delays, such as telemedicine, which cannot meet the requirements of molecular information transmission.

Summary of the invention

In view of this, an embodiment of the present application provides a microelectronic integrated device and a molecular information detection method, aiming to improve the detection efficiency of molecular information of the microelectronic integrated device.

The technical solution of the embodiment of the present application is implemented as follows:

In a first aspect, an embodiment of the present application provides a microelectronic integrated device, including:

Molecular channels, used to transmit body fluid molecules that carry biological information;

A molecular sensor, used for detecting the concentration of the body fluid molecules transmitted by the molecular channel to obtain an optical signal representing the concentration;

A photodetector, connected to the molecular sensor, for converting the optical signal into an electrical signal;

A wireless communication unit, connected to the photoelectric detector, for wirelessly transmitting the electrical signal;

Wherein, a plurality of magnetically controlled micro-elements with a size of micrometer level are arranged in the molecular channel, and the magnetically controlled micro-elements are used to accelerate the propagation speed of the body fluid molecules in the molecular channel.

In the above solution, the molecular sensor is a nano-fluorescence sensor, the light signal is a fluorescence signal generated by the nano-fluorescence sensor, and the intensity of the fluorescence signal is positively correlated with the concentration.

In the above solution, the magnetically controlled micron element is a rod-shaped metal element with a diameter of nanometer size and a length of micrometer size.

In the above solution, the magnetron micron element is a metal nickel rod.

In the above solution, the length of the metal nickel rod is 10 micrometers and the diameter is 300 nanometers.

In the above solution, the size of the microelectronic integrated device is at the centimeter level.

In the above solution, the microelectronic integrated device is in the shape of a capsule as a whole.

In a second aspect, an embodiment of the present application provides a molecular information detection method based on the microelectronic integrated device according to the first aspect, the method comprising:

placing the microelectronic integrated device in a three-dimensional Helmholtz coil;

The three-dimensional Helmholtz coil is controlled to apply a rotating magnetic field to the space where the microelectronic integrated device is located, so that the magnetically controlled micron element in the molecular channel of the microelectronic integrated device rotates in the molecular channel, thereby accelerating the propagation speed of body fluid molecules in the molecular channel.

In the above solution, controlling the three-dimensional Helmholtz coil to apply a rotating magnetic field to the space where the microelectronic integrated device is located includes:

Alternating current with the same frequency and a phase difference of 90 degrees is applied to two pairs of coils in the horizontal direction of the three-dimensional Helmholtz coil.

In the above solution, the frequency ranges from 0 to 200 Hz, and the magnetic field induction intensity of the rotating magnetic field ranges from 0 to 100 millitesla.

The technical solution provided in the embodiment of the present application is to set a plurality of magnetically controlled micro-elements with a size of micrometer level in the molecular channel of the microelectronic integrated device. The magnetically controlled micro-elements are used to accelerate the propagation speed of body fluid molecules in the molecular channel, so that the body fluid molecules can be quickly identified by the molecular sensor, and the molecular information is transmitted to the in vitro receiving device via the wireless communication unit, thereby realizing the fusion of molecular communication and wireless communication, thereby realizing the wireless transmission of molecular information with a small transmission delay, which is conducive to meeting the requirements of rapid identification and real-time transmission of molecular information in a micro-area environment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a schematic structural diagram of a microelectronic integrated device according to an embodiment of the present application;

FIG2 is a schematic diagram showing the principle of a method for preparing a metal nickel rod in an application example of the present application;

FIG3 is a schematic diagram of a flow chart of a molecular information detection method according to an embodiment of the present application;

FIG4 is a control schematic diagram of a three-dimensional Helmholtz coil according to an embodiment of the present application;

FIG5 is a schematic diagram of simulation results of molecular information detection in the first application example of the present application;

FIG6 is a schematic diagram of simulation results of molecular information detection in the second application example of the present application;

FIG. 7 is a schematic diagram of simulation results of molecular information detection in the first application example of the present application.

Description of reference numerals:

100. Microelectronic integrated devices;

101. Molecular channels;

102. Molecular sensor; 103. Photodetector; 104. Wireless communication unit;

200. In vitro receiving equipment;

300. Three-dimensional Helmholtz coil.

DETAILED DESCRIPTION

The present application is further described in detail below in conjunction with the accompanying drawings and embodiments.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

An embodiment of the present application provides a microelectronic integrated device. As shown in FIG1 , the microelectronic integrated device 100 includes: a molecular channel 101 , a molecular sensor 102 , a photodetector 103 and a wireless communication unit 104 .

The molecular channel 101 is used to transmit body fluid molecules carrying biological information, which are also called information molecules because they carry characteristic indicators of diseases, viruses or bacterial infections. For example, the body fluid molecules can be nucleic acid molecules, protein molecules, blood sugar molecules, etc.

It can be understood that the microelectronic integrated device 100 of the embodiment of the present application can be set in the human body, and accordingly, the tumor cells or viruses in the human body can serve as the transmitter of the microelectronic integrated device 100, that is, the tumor cells or viruses can release specific protein molecules, nucleic acid molecules, etc. into the body fluids. These molecules are propagated to various tissues and organs through the body fluid circulation, and can diffuse to the corresponding molecular sensor 102 through the molecular channel 101, so that molecular information can be identified.

The molecular sensor 102 is used to detect the concentration of body fluid molecules transmitted by the molecular channel 101, obtain a light signal representing the concentration, and further realize the recognition of molecular information.

For example, the molecular information can be encoded in concentration, the molecular sensor 102 can be a nano-fluorescence sensor, the light signal is a fluorescence signal generated by the nano-fluorescence sensor, and the intensity of the fluorescence signal is positively correlated with the concentration. For example, the molecular sensor 102 can be a nano-fluorescence probe, so that the molecular information can be characterized in the form of bioluminescence.

Taking the body fluid molecule as heme molecule as an example, the molecular sensor 102 can adopt a nano fluorescence sensor that is sensitive to heme. In this way, after receiving the heme molecule transmitted through the molecular channel 101, the nano fluorescence sensor can express the molecular information in the form of bioluminescence. The molecular information can be encoded by concentration, and the molecular concentration is positively correlated with the intensity of the fluorescence signal generated by the nano fluorescence sensor.

The photodetector 103 is connected to the molecular sensor 102 and is used to convert the optical signal into an electrical signal. For example, when the intensity of the fluorescent signal is high enough, it can be sensed by the photodetector 103 and the optical signal is converted into an electrical signal.

The wireless communication unit 104 is connected to the photodetector 103 and is used to wirelessly transmit the electrical signal. For example, the wireless communication unit 104 may include a microprocessor chip and an antenna. The microprocessor chip receives the electrical signal converted by the photodetector 103 and sends the electrical signal to the external receiving device 200 via the antenna.

It can be understood that the microelectronic integrated device 100 of the embodiment of the present application combines molecular communication and wireless communication technologies to achieve wireless transmission of molecular information in a microscopic environment, thereby constructing the Internet of Bio-Nano Things (IoBNT).

It should be noted that, in the embodiment of the present application, a plurality of micron-sized magnetically controlled micro-elements are arranged in the molecular channel 101 of the microelectronic integrated device 100, and the magnetically controlled micro-elements are used to accelerate the propagation speed of body fluid molecules in the molecular channel 101. The magnetically controlled micro-elements can accelerate the propagation speed of body fluid molecules in the molecular channel 101 under the action of an external magnetic field, reduce the transmission delay of molecular information, and facilitate meeting the requirements of rapid identification and real-time transmission of molecular information in a micro-area environment.

Exemplarily, the magnetron micro-element is a rod-shaped metal element with a diameter of nanometer size and a length of micrometer size.

It can be understood that the rod-shaped metal element of the above-mentioned size is convenient for arrangement in the molecular channel 101 of the microelectronic integrated device 100, and the rod-shaped metal element, under the action of the external magnetic field, acts as a micro-agitator to enhance the diffusion of body fluid molecules in the molecular channel 101, thereby achieving the purpose of accelerating the propagation speed of body fluid molecules in the molecular channel 101.

Exemplarily, the magnetron micro-element is a metal nickel rod.

Exemplarily, the metal nickel rod has a length of 10 micrometers (um) and a diameter of 300 nanometers (nm).

In an application example, a metal nickel rod can be prepared by a template-assisted electrochemical deposition method. For example, as shown in FIG2 , the preparation method of the metal nickel rod is as follows: an anodic aluminum oxide (AAO) with a pore size of 300 nm is used as a template, a conductive silver paste is coated on one side of the AAO and a copper foil is attached as a working electrode (WE); the AAO is fixed at the bottom of the electrochemical deposition cell, the side without coating is exposed, and the side with copper foil is connected to the working electrode of the electrochemical workstation; 8 mL of Ni(H ₂ NSO ₃ ) ₂ (nickel aminosulfonate) solution is added to the electrochemical deposition cell, and then a platinum electrode (counter electrode, CE) and a silver chloride electrode (reference electrode, RE) are inserted into the electrolyte; a constant current of 20 mA is applied through the electrochemical workstation for 2000 seconds; the AAO template is corroded with a sodium hydroxide solution, and then ultrasonic cleaning and centrifugation are performed to obtain a Ni microrod with a length of about 10 μm and a diameter of 300 nm.

It is understandable that the size of the metal nickel rod can be processed according to actual needs and is not limited to the size shown in the above preparation method.

For example, the size of the microelectronic integrated device 100 may be in the centimeter level, which is convenient for realizing precise targeted therapy and microsurgery in the human body.

Exemplarily, the microelectronic integrated device 100 may be in a capsule shape as a whole.

The embodiment of the present application further provides a molecular information detection method based on the above-mentioned microelectronic integrated device 100, as shown in FIG3, the method includes:

Step 301: placing a microelectronic integrated device in a three-dimensional Helmholtz coil.

Step 302, controlling the three-dimensional Helmholtz coil to apply a rotating magnetic field to the space where the microelectronic integrated device is located, so that the magnetically controlled micron element in the molecular channel of the microelectronic integrated device rotates in the molecular channel, thereby accelerating the propagation speed of body fluid molecules in the molecular channel.

Exemplarily, the above-mentioned microelectronic integrated device 100 is disposed in a human body, and when the human body moves, the microelectronic integrated device 100 in the body may be located in 3D Helmholtz coils.

It is understandable that the three-dimensional Helmholtz coil is a device that can produce a uniform magnetic field in a small area. Since the Helmholtz coil has an open nature, it is easy to place or remove the microelectronic integrated device 100.

Exemplarily, controlling the three-dimensional Helmholtz coil to apply a rotating magnetic field to the space where the microelectronic integrated device is located includes:

Alternating current with the same frequency and a phase difference of 90 degrees is applied to two pairs of coils in the horizontal direction of the three-dimensional Helmholtz coil.

As shown in Fig. 4, a plurality of metal nickel rods (e.g., about 10,000) with a length of 10 μm and a diameter of 300 nm prepared by the above preparation method are introduced into the molecular channel 101 of the microelectronic integrated device 100. Then the entire microelectronic integrated device 100 is placed at the center of the three-dimensional Helmholtz coil 300, and an alternating current with the same frequency and a phase difference of 90 degrees is applied to two pairs of coils in the x-y direction, so that a rotating magnetic field ω can be generated in the horizontal plane, thereby driving the metal nickel rods in the molecular channel 101 to rotate. The rotating metal nickel rods can be used as micro-stirrers to enhance the diffusion of body fluid molecules in the molecular channel 101, thereby achieving the purpose of accelerating the propagation speed of body fluid molecules in the molecular channel 101.

Exemplarily, the rotation rate of the magnetically controlled micron element can be controlled by changing the rotation frequency of the rotating magnetic field, thereby changing the flow rate of the fluid. For example, the rotation frequency of the rotating magnetic field ranges from 0 to 200 Hz, and the magnetic field induction intensity of the rotating magnetic field is 0 to 100 millitesla (mT). The fluid flow rate driven by the rotation of the magnetically controlled micron element can be increased from 0 to about 10 mm/s (millimeter per second). Therefore, the diffusion rate of information molecules (i.e., body fluid molecules) in the molecular channel 101 is accelerated, which sharply shortens the time for the information molecules to reach the receiver (i.e., the molecular sensor 102). The transmission time of information molecules can be shortened from 30 min (minutes) to within 1 s (seconds), thereby realizing the rapid identification and real-time transmission of molecular information by the IoBNT device in a micro-area environment. It is conducive to the accurate and real-time monitoring of human physiological information by the future 6G body area network.

From the above description, it can be known that the embodiment of the present application sets a plurality of magnetically controlled micro-elements with a size of micrometer level in the molecular channel of the microelectronic integrated device. The magnetically controlled micro-elements are used to accelerate the propagation speed of body fluid molecules in the molecular channel, so that the body fluid molecules can be quickly identified by the molecular sensor, and the molecular information is transmitted to the in vitro receiving device via the wireless communication unit, thereby realizing the fusion of molecular communication and wireless communication, thereby realizing the wireless transmission of molecular information with a small transmission delay, which is conducive to meeting the requirements of rapid identification and real-time transmission of molecular information in the micro-area environment.

The following is a specific description in conjunction with an application example:

Application Example 1

In this application example, heme is used as an information molecule, which can be used as a signal molecule for gastrointestinal bleeding. A heme-sensitive nanofluorescence sensor is used as a receiver of molecular information (i.e., molecular sensor 102) to convert molecular information into an optical signal. When the concentration of information molecules at the receiver is high enough, a significant photocurrent change can be caused on the photodetector 103. The molecular channel is designed as a square cross-section with a length and width of 5mm×5mm, and the information molecules diffuse freely depending on the concentration gradient difference between the transmitter and the receiver. The initial concentration is 500ppm (parts per million), the detection limit concentration of the receiver is 32.5ppm, and the diffusion coefficient is 1.6× ^{10-9 m2} /s. The diffusion process and diffusion time of information molecules can be simulated by dilute substance transfer simulation software such as COMSOL, Fluent, etc. The results are shown in Figure 5. It takes 36 minutes for the concentration of information molecules at the receiver to reach 32.5ppm.

Application Example 2

On the basis of the first application example, about 10,000 Ni microrods are added to the molecular channel 101, and the microelectronic integrated device 100 is placed in the three-dimensional Helmholtz coil 300. The magnitude of the applied rotating magnetic field is 5 mT, the frequency is 30 Hz, and the fluid flow rate caused is about 2 mm/s. The simulation results are shown in FIG6. It only takes 2.2 seconds for the information molecule concentration at the receiver to reach 32.5 ppm, which is nearly 1,000 times shorter than the transmission time of the first application example.

Application Example 3

On the basis of the first application example, about 10,000 Ni microrods are added to the molecular channel 101, and the microelectronic integrated device 100 is placed in the three-dimensional Helmholtz coil 300. The magnitude of the applied rotating magnetic field is 5 mT, the rotation frequency is 80 Hz, and the fluid flow rate caused is about 5 mm/s. The simulation results are shown in FIG7 , and it takes 0.9 s for the information molecule concentration at the receiver to reach 32.5 ppm.

It should be noted that the technical solutions described in the embodiments of the present application can be combined arbitrarily without conflict.

The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present application, which should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims (9)

1. A microelectronic integrated device, comprising:

A molecular channel for transmitting body fluid molecules carrying biological information;

the molecular sensor is used for detecting the concentration of the body fluid molecules transmitted by the molecular channel to obtain an optical signal representing the concentration;

the photoelectric detector is connected with the molecular sensor and is used for converting the optical signal into an electric signal;

The wireless communication unit is connected with the photoelectric detector and is used for wirelessly transmitting the electric signal;

A plurality of magnetic control micron elements with micron-sized dimensions are arranged in the molecular channel, and the magnetic control micron elements are used for accelerating the propagation speed of the body fluid molecules in the molecular channel;

the magnetic control micron element adopts a rod-shaped metal element with the diameter of nanometer scale and the length of micron scale.

2. The microelectronic integrated device according to claim 1, wherein,

The molecular sensor is a nano fluorescence sensor, the optical signal is a fluorescence signal generated by the nano fluorescence sensor, and the intensity of the fluorescence signal is positively correlated with the concentration.

3. The microelectronic integrated device according to claim 1, wherein,

The magnetic control micron element is a metal nickel rod.

4. The microelectronic integrated device according to claim 3, wherein,

The length of the metal nickel rod is 10 micrometers, and the diameter is 300 nanometers.

5. The microelectronic integrated device according to any of claims 1 to 4, characterized in that,

The microelectronic integrated device is in the order of centimeters in size.

6. The microelectronic integrated device according to claim 5, wherein,

The microelectronic integrated device is entirely in the form of a capsule.

7. A method of molecular information detection based on a microelectronic integrated device according to any of claims 1 to 6, the method comprising:

Placing the microelectronic integrated device within a three-dimensional helmholtz coil;

and controlling the three-dimensional Helmholtz coil to apply a rotating magnetic field to a space where the microelectronic integrated equipment is located, so that a magnetic control micron element in a molecular channel of the microelectronic integrated equipment rotates in the molecular channel, and further, the propagation speed of body fluid molecules in the molecular channel is accelerated.

8. The method for detecting molecular information in a microelectronic integrated device according to claim 7, wherein the controlling the three-dimensional helmholtz coil to apply a rotating magnetic field to a space in which the microelectronic integrated device is located comprises:

Alternating currents with the same frequency and 90-degree phase difference are applied to the two pairs of coils of the three-dimensional Helmholtz coil in the horizontal direction.

9. The method for molecular information detection of a microelectronic integrated device according to claim 8, wherein,

The frequency is in a range of 0-200 Hz, and the magnetic field induction strength of the rotating magnetic field is 0-100 mTesla.