WO2015106378A1

WO2015106378A1 - Multifunctional medical mems microprobe

Info

Publication number: WO2015106378A1
Application number: PCT/CN2014/070554
Authority: WO
Inventors: 刘胜; 徐涌; 戴宜全
Original assignee: 无锡慧思顿科技有限公司; 武汉飞恩微电子有限公司
Priority date: 2014-01-14
Filing date: 2014-01-14
Publication date: 2015-07-23

Abstract

A multifunctional medical MEMS microprobe, the microprobe being hollow tube-shaped; the hollow needle (5) having arranged therein an optical fiber (1), a microfluidic tube (4), and microelectrodes (2) and microfluidic tube outlets (3) fabricated on the sides of the needle tip; the tail of the probe having a flexible interconnection cable connecting to a control chip or a neural prosthesis control system, and the optical fiber (1) being connected to the tail of an optical fiber coupler (6). All in one, the microprobe has diagnostics, pathogen spectral discrimination, therapeutic efficacy monitoring, nerve impulse communication, and various treatments, and is particularly suitable for use in transdermal administration, nerve impulse signal acquisition and electric shock input, neural prosthesis interconnection, pathogenic cell spectral analysis and discrimination, and electrical breakdown therapy.

Description

Technical field

The invention relates to a medical micro-probe with multiple functions, which is mainly used for clinical diagnosis and neuroprosthetic support interconnection, and can also be used for neural signal feedback control research. Background technique

Although acupuncture is currently used in hundreds of countries and regions, its essence and related skills are sometimes not truly understood. Some Western mainstream academic circles even question the existence of acupuncture points of Chinese medicine, and believe that its efficacy is only a psychological comfort effect and has no substantial effect. On the other hand, TCM theory has non-positive characteristics, and there is no clear understanding of the size of acupoints. There is no quantitative tool and feedback verification system, and research tools are quite lacking. Moreover, as a technique of non-transmission, the acupuncture technique is often referred to as a cumbersome and mysterious name. It is even passed down to the family of the family, which can only be taught, practiced and deepened. For example, even the most basic interpolation and twirling techniques, in which the amplitude, frequency and time of the interpolation are repeated, the angle, frequency and time of the sway are related to the patient's feeling and the doctor's feeling. The problem is this. The so-called "getting angry" induction itself is difficult to understand and accurately understand. Therefore, as an important tool for national defense against cultural attacks, how to construct clinical quality control and efficacy evaluation methods suitable for acupuncture characteristics, it is imperative to display the efficacy of acupuncture with scientific data accepted by international scholars; establish standards and norms for acupuncture therapy, through general clinical practice guidelines Formal promotion is the key to the internationalization of acupuncture.

From the perspective of modern medicine, acupuncture uses physical stimulation to respond to the corresponding parts of the human body and generate bioelectrical signals to the brain. After the brain analyzes and integrates the information, it will make the body Corresponding adjustments sometimes secrete therapeutic neurotransmitters. This series of adjustments affects the state of the entire body, allowing the patient to "self-heal the disease." Based on this idea, the present invention aims to provide a microprobe as a research platform, incorporating transdermal drug delivery, microelectrodes for shock stimulation and brain reaction potential signal collection, spectral efficacy tracking, tip pressure and stress strain measurement, etc. Technology, supporting the scientific quantitative research of acupuncture. Summary of the invention

SUMMARY OF THE INVENTION It is an object of the present invention to provide a multifunctional medical MEMS microprobe incorporating transdermal drug delivery, microelectrodes for shock stimulation and brain response potential signal collection, spectral efficacy tracking, tip pressure and stress strain measurement.

In order to achieve the above object, the present invention adopts the following technical solutions:

A multifunctional medical MEMS microprobe is characterized in that an optical fiber and a micro flow tube are arranged inside the hollow needle tube, and a micro electrode and a micro flow tube outlet are formed on the side of the needle tip, and a flexible interconnection line and a control chip are arranged at the tail of the probe. Or the neuroprosthetic control system is interconnected while the fiber is connected to the fiber optic coupler at the tail. The hollow needle tube may be used singly or in an array, and the material may be silicon or silicon dioxide, metal, or polymer.

The optical fiber is placed inside the hollow needle tube, and the front end is cemented with the front end of the needle, and is sharpened together to serve as a laser exit port.

The microfluidic tube is placed inside the needle tube for drug delivery, wherein a plurality of drug outlets are formed on the side of the needle tip, and a small amount of sustained release agent may also be stored at the outflow port.

The microelectrode is fixed to the outer side of the front end of the needle, and may be one or more for contacting a neuron to achieve nerve stimulation or sensing a nerve pulse signal, and may also be used to form an electric field at a local cell site for electrical breakdown.

The fiber coupler can be compatible with a single fiber single-wavelength laser access or a plurality of lasers with different wavelengths of laser input to realize laser input to the probe. The light source may be a femtosecond laser, a picosecond laser, an infrared laser, a krypton laser or the like according to application requirements. In order to obtain a more suitable wavelength of light, a phase retarder can be added before the laser coupler is connected to modulate the appropriate stimulated Raman input light or diagnostic light to achieve spectral focusing.

The microprobe of the invention has important application value in transdermal administration, microelectrode and the like:

Traditional methods of administration include oral administration and injection. The main problems of oral administration are the degradation of the gastrointestinal tract and the first-pass effect of the liver. Intravenous injection has a painful effect and requires medical personnel to operate. Micro-probe arrays assisted transdermal administration can significantly increase the transdermal rate and absorption of macromolecular drugs, enabling efficient and painless administration. In addition, since the microscopic local lesion tissue identification and drug effect monitoring are still very difficult, the probe of the present invention has the functions of spectrum analysis of infrared spectrum or Raman spectrum, and the spectrum of the diseased cells and normal cells. The difference can identify the location of the lesion and the treatment of the lesion. At the same time, laser acupuncture can also be used with different lasers.

The micro-neural electrode at the front end of the micro-probe can extract neural signals and provide a control communication platform for the disabled, such as Parkinson's, epilepsy, blind people, etc., which is the key to study the human neural feedback signal and connect the intelligent prosthesis. bridge. In addition, cell membrane lipid opening, that is, electroporation, is also a current method for treating cancer, and Raman spectroscopy is particularly effective for identifying cancer cells, and simultaneously binds to probe microtubules. Drug macromolecules are electroporated in cells. In this case, it is easy to enter the interior of the cell, thereby achieving a combination of chemotherapy and electroporation therapy to improve the efficiency of treating cancer and to achieve local treatment.

The invention provides a novel neural probe and probe array. Compared with the conventional probe, the invention can be fabricated by an existing MEMS process such as electrochemical etching, and has low cost, high precision, longer probe and more assembly. The electrodes are subjected to electric shock and feedback to form a three-dimensional electrode array having three-dimensional spatial resolution capability, and at the same time, a micro-flow tube drug delivery function is realized. The experiments that have been completed show that the probe made based on the present invention succeeds when the mouse is in an artificial noise environment. The pulse response potential signals of the two auditory neurons in the brain of the mouse were collected, as shown in Fig. 1 and 2. As can be seen from the figure, the probe has sufficient sensitivity to distinguish different neuronal response signals.

The invention has the beneficial effects that the probe of the invention can combine diagnosis, pathogenic spectrum identification, therapeutic effect monitoring, neural pulse communication and various treatment means, and can be applied to different applications. It is especially suitable for transdermal drug delivery, nerve pulse signal acquisition and shock input, neuroprosthetic interconnection, pathogen cell spectrum analysis and identification, and electrical breakdown therapy. DRAWINGS

Fig.1 Pulse response potential signal of two auditory neurons in the brain of mice

Figure 2: Pulse response signal after effective differential processing with classification program

Figure 3 is a schematic view of the structure of the present invention.

detailed description

As shown in Fig. 1, a multifunctional medical MEMS microprobe, the microprobe tube 5 and the inner fiber 1 are cemented together and sharpened to obtain a microprobe tip. The microelectrode 2 and the microfluidic tube outlet 3 are formed on the outer wall of the front end of the probe, wherein the electrode signal is led out through the gold plating wire in the outer wall groove of the needle tube for external control chip or intelligent prosthesis control system (not shown), and the electrode is The application needs to be used as a neuron stimulation interconnect or to create a breakdown electric field at the local cells; the microfluidic tube outlet is used to contact the medicament in the microfluidic tube 4 or the sustained release medicament pre-existing in the orifice with the affected area. The laser coupler 6 can meet the laser access of different wavelengths, wherein the laser can be a femtosecond laser, a picosecond laser, an infrared laser, a holmium laser, etc., and the selection is determined by the actual medical application. When Raman spectroscopy is used to identify diseased tissue, two different wavelengths of laser light can be coupled into the probe fiber, and one of the lasers can be first connected to the phase retarder before coupling, and the phase retarder can be adjusted in the probe. The wavelength of the input light required for stimulated Raman scattering is generated in the fiber to achieve spectral focusing to improve spectral resolution. In addition, the probe can be used for the collection of the optical signal generated by the excitation. At this time, an avalanche diode, a photoelectric imaging probe, and the like are connected after the laser coupler, so that the space congestion caused by the accessories such as the lens can be greatly avoided.

Claims

Claim

A multifunctional medical MEMS microprobe, characterized in that: the microprobe is in the shape of a hollow needle tube, an optical fiber and a micro flow tube are arranged inside the hollow needle tube, and a micro electrode and a micro flow tube outlet are formed on the side of the needle tip. A flexible interconnecting wire is connected to the control chip or the neuroprosthetic control system at the end of the probe, and the optical fiber is connected to the fiber coupler at the tail.

2. The multifunctional medical MEMS microprobe according to claim 1, wherein: the microprobe has a needle tube made of silicon or silicon dioxide or carbon nanotubes, a single probe, or a microscopic probe. The needle array is used.

The multifunctional medical MEMS microprobe according to claim 1 or 2, wherein: the optical fiber and the probe tip are cemented and sharpened, and the laser is emitted from the front end of the probe; The tail is connected to a fiber coupler, and a single wavelength laser or a plurality of different wavelengths of laser light are coupled into the fiber depending on the application.

The multifunctional medical MEMS microprobe according to claim 3, wherein the laser is a laser for laser acupuncture, a laser for infrared spectrum analysis, or a laser for exciting resonance Raman spectroscopy; Spectra were used for pathological analysis and lesion tissue identification.

The multifunctional medical MEMS microprobe according to claim 1 or 2, wherein: the micro flow tube is placed inside the needle tube for drug delivery, and the micro flow tube outlet is disposed at the side of the needle tip at the exit Store a small amount of sustained release agent.

The multifunctional medical MEMS microprobe according to claim 1 or 2, wherein: the microelectrode is fixed to an outer side of the front end of the needle, one or more, for contacting the neuron to achieve nerve stimulation, The nerve impulse signal is sensed or used to form an electric field at a localized cellular site for electrical breakdown.