CN104939843B - Implanted cancer relapse real-time monitoring system - Google Patents

Implanted cancer relapse real-time monitoring system Download PDF

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CN104939843B
CN104939843B CN201510406415.3A CN201510406415A CN104939843B CN 104939843 B CN104939843 B CN 104939843B CN 201510406415 A CN201510406415 A CN 201510406415A CN 104939843 B CN104939843 B CN 104939843B
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circulation
free rna
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CN104939843A (en
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杨承刚
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Qingdao Yangshen Biomedical Co Ltd
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Beijing Medintell Bioinformatic Technology Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813Specially adapted to be attached to a specific body part
    • A61B5/6824Arm or wrist
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient ; user input means
    • A61B5/742Details of notification to user or communication with user or patient ; user input means using visual displays
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient ; user input means
    • A61B5/7455Details of notification to user or communication with user or patient ; user input means characterised by tactile indication, e.g. vibration or electrical stimulation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient ; user input means
    • A61B5/746Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms

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Abstract

The invention discloses an implanted cancer relapse real-time monitoring system. The monitoring system comprises an in-vivo implantation assembly and an in-vitro assembly, wherein the in-vivo implantation assembly can convert concentration information of circulating cell-free nucleic acids in a tissue fluid into transmittal digital information and transmit the digital information to the in-vitro assembly in a wireless transmission manner; the in-vitro assembly analyzes the received circulating cell-free nucleic acid information and informs a user of the implanted cancer relapse real-time monitoring system of paying attention to cancer relapse danger in an information display or warning manner. The implanted cancer relapse real-time monitoring system can monitor a molecular marker, circulating cell-free nucleic acids, of cancer relapse/transfer in real time and can detect the cancer relapse danger in an early stage of cancer relapse, so that a patient suffering from cancer relapse can be treated in time.

Description

A kind of implanted cancer return real-time monitoring system
Technical field
The invention belongs to medical instruments field, it is related to a kind of cancer return monitoring system, and in particular to a kind of implanted cancer Disease recurs real-time monitoring system.
Background technology
The curative competence of current China cancer is also not fully up to expectations, and about 1/3 can be controlled in whole cancer patients More, the chance of long term survival is obtained, but there are relapse and metastasis in the course of disease in the cancer patient for also having half or so.Cancer return is The cancer that finger is brought under control occurs on primary organ again, or cancer invades lymph vessels or body cavity from original site, moves Elsewhere continued growth is moved on to, is formed and the same type of tumour of primary tumor.Some cancers can be in some months after treating first Or recurred after several years.Therefore for cancer patient, the monitoring for carrying out postoperative recurrence transfer is very important.Cancer return It is more early that the sign of transfer finds, it becomes possible to takes counter-measure in time, the effective possibility for suppressing cancer return transfer, prolongs Cancer patient long postoperative life cycle.
The free RNA (circulating cell-free nucleic acids) of circulation refers to be present in human circulation system In system, extracellular micro endogenous or Exogenous Nucleic Acid fragment, including core DNA, mitochondrial DNA are free on (mitochondrial DNA, mitDNA), viral DNA, mRNA (messenger RNA, mRNA) and Microrna (microRNA, the free RNA of circulation) etc..MRNA stability in itself is relatively low, while the RNase level liter in tumor patient blood Height, therefore previously think that circulation free mRNA degradation speed is very fast, clinical value is limited.There is research to be disclosed in tumor patient Serum in, RNA exists with fat egg from the form of complex.It is another studies have found that, free mRNA multi-source is deposited in Apoptosis In being apoptotic body, therefore free mRNA stability in tumor patient blood is higher.These features all examine free mRNA Survey is applied to clinic becomes possibility.Research discovery, can detect cyclin D 1mRNA in the blood plasma of patient with breast cancer Patient the overall survival patient negative significantly lower than blood plasma cyclin D1mRNA;Prognosis is pointed out in clinical pathologic characteristic In preferable patient, patient's prognosis that cyclin D 1mRNA are detected in blood plasma is poor;In the patient of his silent former times fragrant treatment, blood The patient of the overall survival significantly lower than cyclin D1mRNA feminine genders of slurry cyclin D 1mRNA positive patient.Additionally, grinding Study carefully discovery plasma of patients with nasopharyngeal carcinoma mRNA integrality reductions, plasma free mRNA integralities substantially rise after radiotherapy, the trip of rising Can be used as the index of disease amelioration from mRNA level in-site.The studies above achievement shows that the mRNA dissociated in blood can turn into cancer morning Phase diagnosis, the molecular marker of relapse and metastasis monitoring.
MiRNA plays an important roll in gene expression, post-transcriptional control, and may play proto-oncogene or tumor suppressor gene Effect.They have high stability in plasma or serum, and the generation, development with tumour are closely related, and these speciality make Free RNA must be circulated as a kind of potential tumor markers.It is found that circulation trip in kinds of tumors blood samples of patients at present From the abnormal change of rna level.MiR-155, miR-202, miR-425, miR-302b and miR-125b etc. are to report in recent years The expression in healthy population and plasma of breast cancer patients or serum have the free RNA of the circulation of notable difference, in the morning of breast cancer There is potential value in phase examination;Additionally, levels of the miR-115 in hormone-sensitive and the insensitive blood serum of patients with human breast carcinoma of hormone Variant, miR-10b levels in the patients serum of estrogen receptor negative are raised.For colorectal cancer patients, miR-92a is in morning Sensitiveness higher has been embodied in phase detection;The rising of miR-21, the reduction of miR34a also have diagnosis effect higher; MiR-141 and miR-221 are then considered as related to poor prognosis.
The mode of current patient monitoring cancer return is mainly periodically to be checked to hospital, this mode for patient, One is inconvenient, expends the time, and two is to check not in time, it is possible to miss the possibility of early detection cancer return.For side Just cancer patient can timely check oneself the recurrence of cancer, study a kind of equipment that can be recurred with real-time monitoring cancer patient It is necessary.
The content of the invention
In order to solve the deficiencies in the prior art, it is an object of the invention to provide a kind of implanted cancer return real-time monitoring System, the monitoring system is by monitoring monitoring of the level completion of the free RNA of circulation in hypodermis liquid to cancer return.Institute State monitoring system and one threshold value of the free RNA of circulation is set, when the level of the free RNA of the circulation for detecting is up to or over this During threshold value, the monitoring system can then notify that monitoring system wearer cancer return may have been sent out by way of sending alarm Raw, cancer patient can enable the state of an illness to be controlled early to be made a definite diagnosis to hospital in time.
To achieve these goals, this invention takes following technical scheme:
The invention provides a kind of implanted cancer return real-time monitoring system, the cancer return real-time monitoring system bag Include et al. Ke component 1 and external component 2;The et al. Ke component 1 includes the free RNA sensors 11, data processing of circulation Module 12, the first wireless communication module 13;The data processing module 12 includes input interface 121, microprocessor 122, output Interface 123, reactor 124;The input interface 121 receives the electrochemical signals of the free output of RNA sensors 11 of the circulation And it is converted into the microprocessor 122 is input into after data signal, the microprocessor 122 carries out agreement to data signal and turns The external component 2 is uploaded to via first wireless communication module 13 by the output interface 123 after changing;It is described external Component 2 include data receiver 21, the data receiver 21 include controller 211, display 212, siren 213, Second wireless communication module 214;The controller 211 receives and analyzes the free RNA of circulation that the et al. Ke component 1 is uploaded Signal, will show, the analysis program of the controller 211 sets afterwards in the free RNA information transmissions of circulation to the display 212 A threshold value is put, when the level of the free RNA of circulation exceedes the threshold value, the controller 211 issues instructions to the siren 213, the siren 213 sends alarm, notifies that wearer notes the danger of cancer return, second wireless communication module On 214 reactors 124 for passing in the et al. Ke component 1 control command of the controller 211, the reaction Device 124 controls unlatching or the resting state of the free RNA sensors 11 of the circulation, when the free RNA sensors 11 of the circulation are stopped During dormancy, the free RNA sensors 11 of circulation carry negative electricity, and RNA free with the circulation with negative electricity does not occur association reaction, when described When the free RNA sensors 11 of circulation are opened, the free RNA sensors 11 of the circulation are not charged, free with the circulation with negative electricity There is association reaction in RNA, the free RNA of electronegative circulation causes the electrical conductivity of the free RNA sensors 11 of the circulation to become Change, so as to the concentration information that will circulate free RNA is converted into electrochemical signals.
Further, the external component 2 also includes intelligent mobile terminal equipment 22, and the data receiver 21 also includes 3rd wireless communication module 215, the controller 211 will circulate free RNA information and pass through the 3rd wireless communication module 215 It is sent in the intelligent mobile terminal equipment 22.
The intelligent mobile terminal equipment 22 can be smart mobile phone, flat board or computer.
Further, the siren 213 is vibrator, notifies that wearer notes the danger of cancer return by way of vibration Danger.
Further, the siren 213 is photophore, notifies that wearer notes the danger of cancer return by way of luminous Danger.
Further, the free RNA sensors 11 of the circulation include the free RNA trapping layer 111, hybridization signal inductive layer of circulation 112.The free RNA trapping layer 111 of circulation is sticked on the hybridization signal inductive layer 112.The free RNA captures of circulation Layer 111 is made up of the capture probe specifically bound with the free RNA of circulation.
The capture probe that the RNA free with circulation that the present invention is used specifically binds can be DNA, RNA, peptide nucleic acid or Lock nucleic acid, as long as the probe being capable of RNA specific bindings free with circulation.RNA free for the circulation of known array comes Say, those skilled in the art are routine techniques according to the capture probe that the free RNA sequence design of circulation hybridizes therewith.Preferably, The capture probe is peptide nucleic acid (PNA).
PNA is the nucleic acid analog that a class replaces ribose (or deoxyribose) phosphate backbone with many phthalein amine chains, with structure Stabilization, not by nuclease and proteasome degradation, can with base complementrity mode and single nucleic acid strands, cytotoxicity low, electroneutral The features such as.PNA has stronger adhesion with DNA, RNA, there is good specific and higher sensitivity, and due to it The property of electroneutral causes PNA-DNA, and the double-strand of PNA-RNA is more stable, and with corresponding DNA-DNA, DNA-RNA double-strands are compared, With melting temperature higher.Due to the structural stability of PNA so that it can in various chemical reagent stable existence, can Neutralized within the scope of temperature wider with being stably present in sour environment.Therefore, PNA can be widely applied to pathogen, hereditary disease In the molecule hybridization of detection, in situ hybridization, mutation analysis, anticancer, antiviral antisense nucleic acids research and application.
Further, the hybridization signal inductive layer 112 is included by silicon nanowire array.The hybridization signal inductive layer 112 It is on using the silicon nanowires of conventional semiconductors technology processing, by silylation modification, surface unimolecule film layer self assembly work Sequence is prepared from, and being fixed by capture probe can form the free RNA sensors of described circulation.The free RNA sensors of circulation Preparation process be well known to those skilled in the art.
Further, first wireless communication module 13, second wireless communication module 214, the 3rd channel radio Letter module 215 is using any one in Bluetooth protocol or Zigbee protocol.
Further, the data receiver 12 can be worn at any part on cancer patient's body, preferably wear In wrist.In addition, the data receiver 12 can not also be worn on a certain position of the body of cancer patient, but make For in vitro accessory is used.
Further, the control of unlatching or the dormancy to the free RNA sensors of circulation is realized in the timing of the controller 211.Control The interval time that system order is assigned continuously adjustabe between 1s to 1800s, regulation stepping is 2s.
The species that can be used for the free RNA of circulation of the invention is that those have significant correlation between cancer to be detected The free RNA of circulation, i.e., by detecting that the concentration of the free RNA of circulation is that can determine whether whether cancer recurs.The free RNA bags of circulation Include circulation free mRNA, the free miRNA of circulation.
Preferably, it is the free miRNA of circulation to circulate free RNA.
The application method of implanted cancer return real-time monitoring system of the invention:
First, the implanted cancer return real-time monitoring system is controlled in a dormant state by the controller 211, Free RNA sensors 11 are now circulated with negative electricity (institute is electrically charged atomic weak, will not be damaged to human body), by et al. Ke Component implantation is subcutaneous;
Secondly, the implanted cancer return real-time monitoring system is opened by the controller 211, circulation is dissociated RNA sensors 11 are not charged, and the free RNA of the now circulation in tissue fluid can be combined with the free RNA sensors 11 of circulation;
Finally, after reaction certain hour, closing implanted cancer return real-time monitoring system by the controller 211 makes Be again at resting state, now circulate free RNA sensors 11 and carry negative electricity, RNA free with circulation is sensed in tissue fluid The free RNA of circulation that device 11 is combined is separated with the free RNA sensors 11 of circulation, the implanted cancer return real-time monitoring system For detection next time is ready.
Cancer patient is known by observing the reaction for circulating free RNA information and siren 213 on display 212 Whether cancer recurs.
The prior art indicate that the free RNA of the circulation dissociated in blood can be used as the potential source biomolecule for detecting all kinds of cancers and disease Label, for the detection of the early detection and cancer return of patient's peripheral blood cancer.Tissue fluid is blood plasma from capillary wall Filter and formed, in addition to without macro-molecular protein, other compositions are substantially identical with blood plasma.Therefore dissociate present in blood The free RNA of circulation is equally existed in tissue fluid, therefore by detecting that the level of the free free RNA of circulation in tissue fluid can use Early detection and the detection of cancer return in cancer, act on the same with blood.
The advantages of the present invention:
1st, implanted cancer return real-time monitoring system of the invention is dissociated rna level by detecting the circulation in tissue fluid Whether recurred to judge that cancer patient is postoperative, the diagnosis of molecular level be able to can find in recurrence early stage, be it is effective and When take corresponding treatment means provide diagnostic base.
2nd, implanted cancer return real-time monitoring system of the invention can be realized monitoring anywhere or anytime, reach dynamic in real time The purpose of state monitoring, can make cancer patient easily timely grasp the current intelligence of cancer return transfer.
3rd, implanted cancer return real-time monitoring system of the invention is a monitoring system that can be reused, the prison Examining system realizes the unlatching of monitoring system or cutting for resting state by controlling the charging property of the free RNA sensors of circulation Change, it is to avoid often detect once needs the operation for being implanted into monitoring system again afterwards.
Brief description of the drawings
Fig. 1 shows a kind of structural representation of implanted cancer return real-time monitoring system of the invention;
A kind of structural representation of Fig. 2 display display implanted cancer return real-time monitoring systems of the invention;
Fig. 3 shows the structural representation of the free RNA sensors of circulation of the invention;
Wherein, 1:Et al. Ke component;11:The free RNA sensors of circulation;111:The free RNA trapping layer of circulation;112:It is miscellaneous Hand over induction of signal layer;12:Data processing module;121:Input interface;122:Microprocessor;123:Output interface;124:Reaction Device;13:First wireless communication module;2:External component;21:Data receiver;211:Controller;212:Display;213: Siren;214:Second wireless communication module;215:3rd wireless communication module;22:Intelligent mobile terminal equipment.
Specific embodiment
Below in conjunction with specific embodiment, the present invention is furture elucidated.It should be understood that these embodiments are merely to illustrate the present invention Rather than limitation the scope of the present invention.
A kind of implanted cancer return real-time monitoring system of embodiment 1
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system includes et al. Ke component 1 With external component 2;Et al. Ke component 1 includes the free RNA sensors 11, data processing module 12 of circulation, the first radio communication Module 13;Data processing module 12 includes input interface 121, microprocessor 122, output interface 123;Reactor 124;Input connects Mouthfuls 121 electrochemical signals for receiving the free output of RNA sensors 11 of circulation and by it be converted into data signal after be input into microprocessor Device 122, microprocessor 122 passes through output interface 123 via the first wireless communication module after protocol conversion is carried out to data signal 13 are uploaded to external component 2;External component 2 includes data receiver 21, and data receiver 21 includes controller 211, shows Show device 212, siren 213, the second wireless communication module 214;Controller 211 is received and analyzes the upload of et al. Ke component 1 The free RNA signals of circulation, will show, the analysis journey of controller 211 in the free RNA information transmissions of circulation to display 212 afterwards Sequence sets a threshold value, and when the level of the free RNA of circulation exceedes the threshold value, controller 211 issues instructions to the siren 213, siren 213 sends alarm, notifies that wearer notes the danger of cancer return, and the second wireless communication module 214 will control On the reactor 124 that the control command of device 211 is passed in et al. Ke component 1, the free RNA sensings of the control circulation of reactor 124 The unlatching of device 11 or resting state, when free RNA 11 dormancy of sensor of circulation, the free RNA sensors of circulation carry negative electricity, with There is no association reaction in the free RNA of the circulation with negative electricity, when the free RNA sensors 11 of circulation are opened, the free RNA of circulation is passed Sensor 11 is not charged, and RNA free with the circulation with negative electricity occurs association reaction, and the free RNA of electronegative circulation causes circulation The electrical conductivity of free RNA sensors 11 changes, so as to the concentration information that will circulate free RNA is converted into electrochemical signals.
Siren 213 is vibrator, notifies that wearer notes the danger of cancer return by way of vibration.
The free RNA sensors 11 of circulation include the free RNA trapping layer 111, hybridization signal inductive layer 112 of circulation.Institute Stating the free RNA trapping layer 111 of circulation is made up of the capture probe specifically bound with the free RNA of circulation.Capture probe is peptide Nucleic acid (PNA).
Hybridization signal inductive layer 112 includes silicon nanowire array.Hybridization signal inductive layer 112 is to utilize conventional semiconductors On the silicon nanowires of technology processing, it is prepared from by silylation modification, surface unimolecule film layer self assembly operation, by capture Probe is fixed can form the free RNA sensors 11 of circulation.The preparation process of the free RNA sensors 11 of circulation is art technology Known to personnel.
First wireless communication module 13, the second wireless communication module 214 use Bluetooth protocol.
Data receiver 12 can be worn at any part on cancer patient's body, for example, be worn in wrist.
The control of unlatching or the dormancy to the free RNA sensors of circulation is realized in the timing of controller 211.What control command was assigned Interval time continuously adjustabe between 1s to 1800s, regulation stepping is 2s.
The free RNA of circulation in the present embodiment refers to miRNA.
The application method of above-mentioned implanted cancer return real-time monitoring system:
1st, implanted cancer return real-time monitoring system is controlled in a dormant state by controller 211, now circulation trip From RNA sensors 11 with negative electricity (institute is electrically charged atomic weak, will not be damaged to human body), et al. Ke component is implanted into skin Under;
2nd, implanted cancer return real-time monitoring system is opened by controller 211, makes the free RNA sensors 11 of circulation not Powered, the free RNA of circulation now in tissue fluid can be combined with the free RNA sensors 11 of circulation;
3rd, after reaction certain hour, implanted cancer return real-time monitoring system is closed by controller 211 and is allowed to again In a dormant state, free RNA sensors 11 are now circulated and carries negative electricity, with the free knot of RNA sensors 11 of circulation in tissue fluid The free RNA of the circulation of conjunction is separated with the free RNA sensors 11 of circulation, and implanted cancer return real-time monitoring system is next time Detection is ready.
4th, by observing whether the free RNA information of the circulation shown on display 212 and siren are vibrated, cancer patient Know whether cancer recurs.
A kind of implanted cancer return real-time monitoring system of embodiment 2
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system includes et al. Ke component 1 With external component 2;Et al. Ke component 1 includes the free RNA sensors 11, data processing module 12 of circulation, the first radio communication Module 13;Data processing module 12 includes input interface 121, microprocessor 122, output interface 123;Reactor 124;Input connects Mouthfuls 121 electrochemical signals for receiving the free output of RNA sensors 11 of circulation and by it be converted into data signal after be input into microprocessor Device 122, microprocessor 122 passes through output interface 123 via the first wireless communication module after protocol conversion is carried out to data signal 13 are uploaded to external component 2;External component 2 includes data receiver 21, and data receiver 21 includes controller 211, shows Show device 212, siren 213, the second wireless communication module 214;Controller 211 is received and analyzes the upload of et al. Ke component 1 The free RNA signals of circulation, will show, the analysis journey of controller 211 in the free RNA information transmissions of circulation to display 212 afterwards Sequence sets a threshold value, and when the level of the free RNA of circulation exceedes the threshold value, controller 211 issues instructions to the siren 213, siren 213 sends alarm, notifies that wearer notes the danger of cancer return, and the second wireless communication module 214 will control On the reactor 124 that the control command of device 211 is passed in et al. Ke component 1, the free RNA sensings of the control circulation of reactor 124 The unlatching of device 11 or resting state, when free RNA 11 dormancy of sensor of circulation, the free RNA sensors 11 of circulation carry negative electricity, There is no association reaction in RNA free with the circulation with negative electricity, when the free RNA sensors 11 of circulation are opened, the free RNA of circulation Sensor 11 is not charged, and RNA free with the circulation with negative electricity occurs association reaction, and the free RNA of electronegative circulation causes to follow The electrical conductivity toured around from RNA sensors 11 changes, so as to the concentration information that will circulate free RNA is converted into electrochemistry letter Number.
Siren 213 is photophore, notifies that wearer notes the danger of cancer return by way of luminous.
The free RNA sensors 11 of circulation include the free RNA trapping layer 111, hybridization signal inductive layer 112 of circulation.Institute Stating the free RNA trapping layer 111 of circulation is made up of the capture probe specifically bound with the free RNA of circulation.Capture probe is peptide Nucleic acid (PNA).
Hybridization signal inductive layer 112 is constituted including silicon nanowire array.Hybridization signal inductive layer 112 is using tradition half On the silicon nanowires of conductor technology processing, it is prepared from by silylation modification, surface unimolecule film layer self assembly operation, is passed through Capture probe is fixed can form the free RNA sensors 11 of circulation.The preparation process of the free RNA sensors 11 of circulation is this area Known to technical staff.
First wireless communication module 13, the second wireless communication module 214 use Zigbee protocol.
Data receiver 12 is used as in vitro accessory.
The control of unlatching or the dormancy to the free RNA sensors 11 of circulation is realized in the timing of controller 211.Control command is assigned Interval time between 1s to 1800s continuously adjustabe, regulation stepping be 2s.
The free RNA of circulation in the present embodiment refers to circulation free mRNA.
The application method of above-mentioned implanted cancer return real-time monitoring system:
1st, implanted cancer return real-time monitoring system is controlled in a dormant state by controller 211, now circulation trip From RNA sensors 11 with negative electricity (institute is electrically charged atomic weak, will not be damaged to human body), et al. Ke component is implanted into skin Under;
2nd, implanted cancer return real-time monitoring system is opened by controller 211, makes the free RNA sensors 11 of circulation not Powered, the free RNA of circulation now in tissue fluid can be combined with the free RNA sensors 11 of circulation;
3rd, after reaction certain hour, implanted cancer return real-time monitoring system is closed by controller 211 and is allowed to again In a dormant state, free RNA sensors 11 are now circulated and carries negative electricity, with the free knot of RNA sensors 11 of circulation in tissue fluid The free RNA of the circulation of conjunction is separated with the free RNA sensors 11 of circulation, and implanted cancer return real-time monitoring system is next time Detection is ready.
4th, by observing whether the free RNA information of the circulation shown on display 212 and siren light, cancer patient Know whether cancer recurs.
A kind of implanted cancer return real-time monitoring system of embodiment 3
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system includes et al. Ke component 1 With external component 2;Et al. Ke component 1 includes the free RNA sensors 11, data processing module 12 of circulation, the first radio communication Module 13;Data processing module 12 includes input interface 121, microprocessor 122, output interface 123;Reactor 124;Input connects Mouthfuls 121 electrochemical signals for receiving the free output of RNA sensors 11 of circulation and by it be converted into data signal after be input into microprocessor Device 122, microprocessor 122 passes through output interface 123 via the first wireless communication module after protocol conversion is carried out to data signal 13 are uploaded to external component 2;External component 2 includes data receiver 21, intelligent mobile terminal equipment 22;Data receiver 21 include controller 211, display 212, siren 213, the second wireless communication module 214, the 3rd wireless communication module 215; Controller 211 is received and analyzes the free RNA signals of circulation of the upload of et al. Ke component 1, afterwards passes the free RNA information of circulation Display on display 212 is sent to, the analysis program of controller 211 sets a threshold value, is somebody's turn to do when the level of the free RNA of circulation exceedes During threshold value, controller 211 issues instructions to the siren 213, and siren 213 sends alarm, notifies that wearer notes cancer The danger of recurrence, the reaction that the second wireless communication module 214 passes in et al. Ke component 1 control command of controller 211 On device 124, the control of reactor 124 circulates unlatching or the resting state of free RNA sensors 11, when the free RNA sensors of circulation During 11 dormancy, the free RNA sensors of circulation carry negative electricity, and RNA free with the circulation with negative electricity does not occur association reaction, when following Tour around from RNA sensors 11 open when, the free RNA sensors of circulation are not charged, and RNA free with the circulation with negative electricity is tied Reaction is closed, the electronegative free RNA of circulation causes the electrical conductivity for circulating free RNA sensors to change, so as to circulation be swum Concentration information from RNA is converted into electrochemical signals.
Controller 211 will circulate free RNA information and be sent to intelligent mobile terminal by the 3rd wireless communication module 215 and set On standby 22.The free RNA information of 22 pairs of circulations of intelligent mobile terminal equipment carries out remote storage and analysis.
Intelligent terminal 22 can be smart mobile phone, flat board or computer.
Data receiver 12 can be worn on any part of cancer patient's body, for example wrist.
First wireless communication module 13, the second wireless communication module 214, the 3rd wireless communication module 215 are assisted using bluetooth View.
Siren 213 is vibrator, notifies that wearer notes the danger of cancer return by way of vibration.
The free RNA sensors 11 of circulation include the free RNA trapping layer 111, hybridization signal inductive layer 112 of circulation.Circulation trip From RNA trapping layer 111 it is made up of the capture probe specifically bound with the free RNA of circulation.Capture probe is peptide nucleic acid (PNA)。
Hybridization signal inductive layer 112 is constituted including silicon nanowire array.Hybridization signal inductive layer 112 is using tradition half On the silicon nanowires of conductor technology processing, it is prepared from by silylation modification, surface unimolecule film layer self assembly operation, is passed through Capture probe is fixed can form the free RNA sensors of circulation.The preparation process of the free RNA sensors of circulation is art technology Known to personnel.
The control of unlatching or the dormancy to the free RNA sensors of circulation is realized in the timing of controller 211.What control command was assigned Interval time continuously adjustabe between 1s to 1800s, regulation stepping is 2s.
The free RNA of circulation in the present embodiment refers to circulating tumor miRNA.
The application method of above-mentioned implanted cancer return real-time monitoring system:
1st, implanted cancer return real-time monitoring system is controlled in a dormant state by controller 211, now circulation trip From RNA sensors 11 with negative electricity (institute is electrically charged atomic weak, will not be damaged to human body), et al. Ke component is implanted into skin Under;
2nd, implanted cancer return real-time monitoring system is opened by controller 211, makes the free RNA sensors 11 of circulation not Powered, the free RNA of circulation now in tissue fluid can be combined with the free RNA sensors 11 of circulation;
3rd, after reaction certain hour, implanted cancer return real-time monitoring system is closed by controller 211 and is allowed to again In a dormant state, free RNA sensors 11 are now circulated and carries negative electricity, with the free knot of RNA sensors 11 of circulation in tissue fluid The free RNA of the circulation of conjunction is separated with the free RNA sensors 11 of circulation, and implanted cancer return real-time monitoring system is next time Detection is ready.
4th, by observe the free RNA information of circulation or intelligent mobile terminal equipment 22 that are shown on display 212 and Whether siren 213 vibrates, and cancer patient knows whether cancer recurs.
A kind of implanted cancer return real-time monitoring system of embodiment 4
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system includes et al. Ke component 1 With external component 2;Et al. Ke component 1 includes the free RNA sensors 11, data processing module 12 of circulation, the first radio communication Module 13;Data processing module 12 includes input interface 121, microprocessor 122, output interface 123;Reactor 124;Input connects Mouthfuls 121 electrochemical signals for receiving the free output of RNA sensors 11 of circulation and by it be converted into data signal after be input into microprocessor Device 122, microprocessor 122 passes through output interface 123 via the first wireless communication module after protocol conversion is carried out to data signal 13 are uploaded to external component 2;External component 2 includes data receiver 21, intelligent mobile terminal equipment 22;Data receiver 21 include controller 211, display 212, siren 213, the second wireless communication module 214, the 3rd wireless communication module 215; Controller 211 is received and analyzes the free RNA signals of circulation of the upload of et al. Ke component 1, afterwards passes the free RNA information of circulation It is sent on display and shows, the analysis program of controller 211 sets a threshold value, when the level of the free RNA of circulation exceedes the threshold During value, controller 211 issues instructions to the siren 213, and siren 213 sends alarm, notifies that wearer notices that cancer is answered The danger of hair, the reactor that the second wireless communication module 214 passes in et al. Ke component 1 control command of controller 211 On 124, the control of reactor 124 circulates unlatching or the resting state of free RNA sensors 11, when the free RNA sensors 11 of circulation During dormancy, the free RNA sensors of circulation carry negative electricity, and RNA free with the circulation with negative electricity does not occur association reaction, works as circulation When free RNA sensors 11 are opened, the free RNA sensors of circulation are not charged, and RNA free with the circulation with negative electricity is combined Reaction, the electronegative free RNA of circulation causes the electrical conductivity for circulating free RNA sensors to change, so as to circulation is free The concentration information of RNA is converted into electrochemical signals.
Controller 211 will circulate free RNA information and be sent to intelligent mobile terminal by the 3rd wireless communication module 215 and set On standby 22.The free RNA information of 22 pairs of circulations of intelligent mobile terminal equipment carries out remote storage and analysis.
Intelligent terminal 22 can be smart mobile phone, flat board or computer.
Data receiver 12 is used as in vitro accessory.
First wireless communication module 13, the second wireless communication module 214, the 3rd wireless communication module 215 use ZigBee Agreement.
Siren 213 is photophore, notifies that wearer notes the danger of cancer return by way of luminous.
The free RNA sensors 11 of circulation include the free RNA trapping layer 111, hybridization signal inductive layer 112 of circulation.Circulation trip From RNA trapping layer 111 it is made up of the capture probe specifically bound with the free RNA of circulation.Capture probe is peptide nucleic acid (PNA)。
Hybridization signal inductive layer 112 includes silicon nanowire array.Hybridization signal inductive layer 112 is to utilize conventional semiconductors On the silicon nanowires of technology processing, it is prepared from by silylation modification, surface unimolecule film layer self assembly operation, by capture Probe is fixed can form the free RNA sensors 11 of circulation.The preparation process of the free RNA sensors 11 of circulation is art technology Known to personnel.
The control of unlatching or the dormancy to the free RNA sensors 11 of circulation is realized in the timing of controller 211.Control command is assigned Interval time between 1s to 1800s continuously adjustabe, regulation stepping be 2s.
The free RNA of circulation in the present embodiment refers to circulation free mRNA.
The application method of above-mentioned implanted cancer return real-time monitoring system:
1st, implanted cancer return real-time monitoring system is controlled in a dormant state by controller 211, now circulation trip From RNA sensors 11 with negative electricity (institute is electrically charged atomic weak, will not be damaged to human body), et al. Ke component is implanted into skin Under;
2nd, implanted cancer return real-time monitoring system is opened by controller 211, makes the free RNA sensors 11 of circulation not Powered, the free RNA of circulation now in tissue fluid can be combined with the free RNA sensors 11 of circulation;
3rd, after reaction certain hour, implanted cancer return real-time monitoring system is closed by controller 211 and is allowed to again In a dormant state, free RNA sensors 11 are now circulated and carries negative electricity, with the free knot of RNA sensors 11 of circulation in tissue fluid The free RNA of the circulation of conjunction is separated with the free RNA sensors 11 of circulation, and implanted cancer return real-time monitoring system is next time Detection is ready.
4th, by observe the free RNA information of circulation or intelligent mobile terminal equipment 22 that are shown on display 212 and Whether siren 213 lights, and cancer patient knows whether cancer recurs.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that:Not Can these embodiments be carried out with various changes, modification, replacement and modification in the case of departing from principle of the invention and objective, this The scope of invention is limited by claim and its equivalent.

Claims (9)

1. a kind of implanted cancer return real-time monitoring system, it is characterised in that the monitoring system includes et al. Ke component And external component (2) (1);The et al. Ke component (1) includes circulation free RNA sensors (11), data processing module (12), the first wireless communication module (13);The data processing module (12) includes input interface (121), microprocessor (122), output interface (123), reactor (124);The input interface (121) receives the free RNA sensors of the circulation (11) electrochemical signals of output and it is converted into after data signal it is input into the microprocessor (122), the microprocessor (122) output interface (123) is passed through via first wireless communication module after protocol conversion is carried out to data signal (13) it is uploaded to the external component (2);The external component (2) includes data receiver (21), and the data receiver sets Standby (21) include controller (211), display (212), siren (213), the second wireless communication module (214);The control Device (211) receives and analyzes the free RNA signals of circulation that the et al. Ke component (1) uploads, afterwards by the free RNA letters of circulation Breath is sent on the display (212) and shows, the analysis program of the controller (211) sets a threshold value, when circulation is swum When exceeding the threshold value from the level of RNA, the controller (211) issues instructions to the siren (213), the siren (213) alarm is sent, notifies that wearer notes the danger of cancer return, second wireless communication module (214) is by the control On the reactor (124) that the control command of device (211) processed is passed in the et al. Ke component (1), the circulation is controlled The unlatching of free RNA sensors (11) or resting state, when free RNA sensor (11) dormancy of the circulation, circulation is free There is no association reaction in RNA sensors (11), with negative electricity, RNA free with the circulation with negative electricity as the free RNA of the circulation When sensor (11) is opened, free RNA sensors (11) is not charged for the circulation, and RNA free with the circulation with negative electricity occurs Association reaction, the free RNA of electronegative circulation causes the electrical conductivity of free RNA sensors (11) of the circulation to change, from And the concentration information that will circulate free RNA is converted into electrochemical signals.
2. monitoring system according to claim 1, it is characterised in that the external component (2) also includes intelligent mobile end End equipment (22), the data receiver (21) also includes the 3rd wireless communication module (215), and the controller (211) will The free RNA information of circulation is sent in the intelligent mobile terminal equipment (22) by the 3rd wireless communication module (215).
3. monitoring system according to claim 1 and 2, it is characterised in that the siren (213) is vibrator, is passed through The mode of vibration notifies that wearer notes the danger of cancer return.
4. monitoring system according to claim 1 and 2, it is characterised in that the siren (213) is photophore, is passed through Luminous mode notifies that wearer notes the danger of cancer return.
5. monitoring system according to claim 1 and 2, it is characterised in that free RNA sensors (11) of the circulation includes Circulation free RNA trapping layer (111), hybridization signal inductive layer (112);Free RNA trapping layer (111) of circulation sticks to institute State on hybridization signal inductive layer (112).
6. monitoring system according to claim 5, it is characterised in that free RNA trapping layer (111) of the circulation be by with The capture probe of the free RNA specific bindings of circulation is constituted.
7. monitoring system according to claim 6, it is characterised in that the capture probe is peptide nucleic acid.
8. monitoring system according to claim 5, it is characterised in that the hybridization signal inductive layer (112) is received including silicon Nanowire arrays.
9. monitoring system according to claim 2, it is characterised in that first wireless communication module (13), described Two wireless communication modules (214), the 3rd wireless communication module (215) are using any in Bluetooth protocol or Zigbee protocol It is a kind of.
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