CN104939843A - Implanted cancer relapse real-time monitoring system - Google Patents

Implanted cancer relapse real-time monitoring system Download PDF

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Publication number
CN104939843A
CN104939843A CN201510406415.3A CN201510406415A CN104939843A CN 104939843 A CN104939843 A CN 104939843A CN 201510406415 A CN201510406415 A CN 201510406415A CN 104939843 A CN104939843 A CN 104939843A
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circulation
rna
monitoring system
free
wireless communication
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CN104939843B (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

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, relate to a kind of cancer return monitoring system, be specifically related to a kind of implanted cancer return real-time monitoring system.
Background technology
The curative competence of current China cancer is also not fully up to expectations, and in whole cancer patient, nearly 1/3 can be cured, and obtains the chance of long term survival, but also has the cancer patient about half to occur relapse and metastasis in the course of disease.Cancer return refers to that the cancer be brought under control occurs again on former hair device official, or cancer invades lymph vessels or body cavity from original site, moves to elsewhere continued growth, forms the tumor with primary tumor same-type.Some cancer can first treatment after some months or recur after several years.Therefore for cancer patient, the monitoring carrying out postoperative recurrence transfer is very important.The sign of cancer return transfer find more early, just can take counter-measure in time, the probability that effective suppression cancer return shifts, the life cycle that prolongation cancer patient is postoperative.
The free RNA (circulating cell-free nucleic acids) of circulation refers to and is present in human recycle system, be free on extracellular micro-endogenous or Exogenous Nucleic Acid fragment, comprise core DNA, mitochondrial DNA (mitochondrial DNA, mitDNA), viral DNA, messenger RNA (messenger RNA, and Microrna (microRNA, circulation free RNA) etc. mRNA).The stability of mRNA itself is lower, and the RNA enzyme level simultaneously in tumor patient blood raises, and therefore previously think that circulation free mRNA degradation speed is very fast, clinical value is limited.Have research to be disclosed in the serum of tumor patient, RNA exists with the form of fat egg from complex.Separately studies have found that, free mRNA multi-source, in apoptosis, is present in apoptotic body, and the free mRNA stability therefore in tumor patient blood is higher.These features all make free mRNA detect to be applied to and clinically become possibility.Research finds, can detect that the overall survival of the patient of cyclin D 1mRNA is starkly lower than the patient of blood plasma cyclin D1mRNA feminine gender in the blood plasma of patient with breast cancer; In the good patient of clinical pathologic characteristic prompting prognosis, the patient's prognosis detecting cyclin D 1mRNA in blood plasma is poor; In the patient of his silent former times sweet smell treatment, the overall survival of the patient of the blood plasma cyclin D 1mRNA positive is starkly lower than the patient of cyclin D1mRNA feminine gender.In addition, research finds that plasma of patients with nasopharyngeal carcinoma mRNA integrity reduces, and after radiotherapy, plasma free mRNA integrity obviously rises, and the free mRNA level of rising can be used as the index of disease amelioration.Above-mentioned achievement in research shows that mRNA free in blood can become the molecular marker of early diagnosis of cancer, relapse and metastasis monitoring.
MiRNA has important function in gene expression, post-transcriptional control, and may play the effect of proto-oncogene or antioncogene.They have high stability in plasma or serum, and with the generation of tumor, develop closely related, these speciality free RNA that makes to circulate becomes a kind of potential tumor markers.In kinds of tumors blood samples of patients, having found the abnormal change of the free rna level of circulation at present.MiR-155, miR-202, miR-425, miR-302b and miR-125b etc. are that expressing in healthy population and plasma of breast cancer patients or serum of reporting in recent years has the circulation of notable difference to dissociate RNA, in the early screening of breast carcinoma, have potential value; In addition, the level of miR-115 in hormone-sensitive and the insensitive blood serum of patients with human breast carcinoma of hormone is variant, and miR-10b level in the patients serum of estrogen receptor negative raises.For colorectal cancer patients, during miR-92a detects in early days, embody higher sensitivity; The rising of miR-21, the reduction of miR34a also have higher diagnosis effect; MiR-141 with miR-221 is then considered to relevant to poor prognosis.
The mode of current patient monitoring cancer return mainly regularly arrives hospital and checks, and this mode is for patient, and one is inconvenient, and expend time in, two is check not in time, likely misses the probability of early discovery cancer return.Conveniently cancer patient can check oneself the recurrence of cancer timely, study a kind of can Real-Time Monitoring cancer patient recurrence equipment be necessary.
Prior art to show in blood that the free circulation RNA that dissociates can be used as the potential source biomolecule label detecting all kinds of cancer and disease, for the earlier detection of patient's peripheral blood cancer and the detection of cancer return.Tissue fluid is that blood plasma filters from capillary wall and formed, and except not containing except macro-molecular protein, other composition is basic identical with blood plasma.Therefore the free circulation existed in the blood RNA that dissociates exists equally in tissue fluid, and namely the level therefore by detecting the free RNA of free circulation in tissue fluid can be used for the earlier detection of cancer and the detection of cancer return, acts on same blood the same.
Advantage of the present invention and beneficial effect:
1, whether implanted cancer return real-time monitoring system of the present invention is judged that cancer patient is postoperative recurred by the circulation detected in the tissue fluid rna level that dissociates, the diagnosis of molecular level can be able to find in early days in recurrence, provides diagnostic base for taking corresponding treatment means effectively and timely.
2, implanted cancer return real-time monitoring system of the present invention can realize monitoring anywhere or anytime, reaches the object of real-time dynamic monitoring, and cancer patient can be made to grasp the current intelligence of cancer return transfer easily timely.
3, implanted cancer return real-time monitoring system of the present invention is a monitoring system that can reuse, this monitoring system realizes the unlatching of monitoring system or the switching of resting state by the dissociate charging property of RNA sensor of controlled circulation, avoids the operation often detecting and once need again to implant monitoring system afterwards.
Summary of the invention
In order to solve the deficiencies in the prior art, the object of the present invention is to provide a kind of implanted cancer return real-time monitoring system, described monitoring system completes the monitoring to cancer return by the level of the free RNA of circulation in monitoring skin undertissue liquid.Described monitoring system arranges the threshold value of a free RNA of circulation, when the circulation detected dissociate the level of RNA reach or exceed this threshold value time, described monitoring system then can notify by the mode given the alarm that monitoring system wearer cancer return may occur, cancer patient just can arrive hospital in time and make a definite diagnosis, and enables the state of an illness obtain control early.
To achieve these goals, this invention takes following technical scheme:
The invention provides a kind of implanted cancer return real-time monitoring system, described cancer return real-time monitoring system comprises et al. Ke assembly 1 and external assembly 2, described et al. Ke assembly 1 comprises circulation free RNA sensor 11, data processing module 12, first wireless communication module 13, described data processing module 12 comprises input interface 121, microprocessor 122, output interface 123, reactor 124, described input interface 121 receive described circulation dissociate RNA sensor 11 export electrochemical signals and input described microprocessor 122 after it is converted into digital signal, be uploaded to described external assembly 2 by described output interface 123 via described first wireless communication module 13 after described microprocessor 122 pairs of digital signals carry out protocol conversion, described external assembly 2 comprises data receiver 21, and described data receiver 21 comprises controller 211, display 212, siren 213, second wireless communication module 214, described controller 211 receives and analyzes circulation that described et al. Ke assembly 1 uploads and to dissociate RNA signal, afterwards free for circulation RNA information is sent on described display 212 and shows, the analysis programme of described controller 211 arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, described controller 211 sends instruction to described siren 213, described siren 213 gives the alarm, notify that wearer notes the danger of cancer return, the control command of described controller 211 passes on the described reactor 124 in described et al. Ke assembly 1 by described second wireless communication module 214, described reactor 124 controls described circulation and to dissociate the unlatching of RNA sensor 11 or resting state, when described circulation dissociates 11 dormancy of RNA sensor, the free RNA sensor 11 of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when described circulation dissociate RNA sensor 11 open time, the described circulation RNA sensor 11 that dissociates is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, the electronegative circulation RNA that dissociates causes the dissociate electrical conductivity of RNA sensor 11 of described circulation to change, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
Further, described external assembly 2 also comprises intelligent mobile terminal equipment 22, described data receiver 21 also comprises the 3rd wireless communication module 215, and free for circulation RNA information is sent in described intelligent mobile terminal equipment 22 by described 3rd wireless communication module 215 by described controller 211.
Described intelligent mobile terminal equipment 22 can be smart mobile phone, flat board or computer.
Further, described siren 213 is vibrators, notifies that wearer notes the danger of cancer return by the mode of vibration.
Further, described siren 213 is luminous organs, notifies that wearer notes the danger of cancer return by the mode of luminescence.
Further, the described circulation RNA sensor 11 that dissociates comprises circulation free RNA trapping layer 111, hybridization signal inductive layer 112.Described circulation RNA trapping layer 111 of dissociating sticks on described hybridization signal inductive layer 112.Described circulation RNA trapping layer 111 of dissociating is made up of the capture probe with the free RNA specific binding of circulation.
The present invention use with the capture probe of the free RNA specific binding of circulation can be DNA, RNA, peptide nucleic acid(PNA) or lock nucleic acid, as long as this probe can to dissociate RNA specific binding with circulation.Circulation for known array dissociates RNA, and the capture probe that those skilled in the art are hybridized with it according to the free RNA sequential design of circulation is routine techniques.Preferably, described capture probe is peptide nucleic acid(PNA) (PNA).
The nucleic acid analog of PNA to be a class with many phthaleins amine chain replace ribose (or deoxyribose) phosphate backbone, have Stability Analysis of Structures, not by nuclease and proteasome degradation, can the feature such as, electric neutrality low with base complementrity mode and single nucleic acid strands, cytotoxicity.PNA and DNA, RNA have stronger adhesion, have good specificity and higher sensitivity, and make PNA-DNA due to its electroneutral character, the double-strand of PNA-RNA is more stable, as compared to corresponding DNA-DNA, DNA-RNA double-strand, there is higher melting temperature.Due to the structural stability of PNA, make it can in number of chemical reagent stable existence, can stably be present in the wider temperature range of sour environment neutralization.Therefore, in the molecular hybridization that PNA can be widely used in pathogen, heredopathia detects, in situ hybridization, mutation analysis, anticancer, antiviral antisense nucleic acids research and application.
Further, described hybridization signal inductive layer 112 comprises by silicon nanowire array.Described hybridization signal inductive layer 112 is on the silicon nanowires utilizing conventional semiconductors technology to process, and is prepared from by silylation modification, surperficial unimolecule rete self assembly operation, fixes can form described circulation and to dissociate RNA sensor through capture probe.The preparation process of the free RNA sensor of circulation is well known to those skilled in the art.
Further, described first wireless communication module 13, described second wireless communication module 214, described 3rd wireless communication module 215 adopt any one in Bluetooth protocol or Zigbee protocol.
Further, described data receiver 12 can be worn at any part on cancer patient's health, is preferably worn in wrist.In addition, described data receiver 12 also can not be worn on a certain position of health of cancer patient, but uses as in vitro accessory.
Further, described controller 211 timing realizes the free unlatching of RNA sensor of circulation or the control of dormancy.The interval time of continuously adjustabe between 1s to 1800s that control command is assigned, adjustment stepping is 2s.
The dissociate kind of RNA of circulation used in the present invention is that the circulation that there is significant correlation between those and cancer to be detected dissociates RNA, and the concentration namely by detecting the free RNA of circulation can judge whether whether cancer recurs.The free RNA of circulation comprises circulation free mRNA, the free miRNA of circulation.
Preferably, the free RNA of circulation is the free miRNA of circulation.
The using method of implanted cancer return real-time monitoring system of the present invention:
First, control described implanted cancer return real-time monitoring system by described controller 211 and be in resting state, et al. Ke assembly, with negative electricity (institute is electrically charged atomic weak, can not damage human body), is implanted subcutaneous by the free RNA sensor 11 of now circulation;
Secondly, open described implanted cancer return real-time monitoring system by described controller 211, make the circulation RNA sensor 11 that dissociates not charged, the RNA that dissociates of the circulation now in tissue fluid can be combined with the free RNA sensor 11 of circulation;
Finally, after reaction certain hour, close implanted cancer return real-time monitoring system by described controller 211 to make it again to be in resting state, the free RNA sensor 11 of now circulation is with negative electricity, the circulation combined with circulation free RNA sensor 11 in tissue fluid RNA and the circulation RNA sensor 11 that dissociates that dissociates is separated, and described implanted cancer return real-time monitoring system is that detection is next time ready.
Cancer patient is dissociated by the circulation on observation display 212 reaction of RNA information and siren 213, knows whether cancer recurs.
Accompanying drawing explanation
Fig. 1 shows a kind of structural representation of implanted cancer return real-time monitoring system of the present invention;
Fig. 2 shows a kind of structural representation of implanted cancer return real-time monitoring system of the present invention;
Fig. 3 shows circulation of the present invention and to dissociate the structural representation of RNA sensor;
Wherein, 1: et al. Ke assembly; 11: the free RNA sensor of circulation; 111: the free RNA trapping layer of circulation; 112: hybridization signal inductive layer; 12: data processing module; 121: input interface; 122: microprocessor; 123: output interface; 124: reactor; 13: the first wireless communication modules; 2: external assembly; 21: data receiver; 211: controller; 212: display; 213: siren; 214: the second wireless communication modules; 215: the three wireless communication modules; 22: intelligent mobile terminal equipment.
Detailed description of the invention
Below in conjunction with specific embodiment, illustrate the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.
Embodiment 1 one kinds of implanted cancer return real-time monitoring systems
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system comprises et al. Ke assembly 1 and external assembly 2, et al. Ke assembly 1 comprises circulation free RNA sensor 11, data processing module 12, first wireless communication module 13, data processing module 12 comprises input interface 121, microprocessor 122, output interface 123, reactor 124, input interface 121 receives electrochemical signals that the free RNA sensor 11 of circulation exports and input microprocessor 122 after it being converted into digital signal, is uploaded to external assembly 2 after microprocessor 122 pairs of digital signals carry out protocol conversion by output interface 123 via the first wireless communication module 13, external assembly 2 comprises data receiver 21, and data receiver 21 comprises controller 211, display 212, siren 213, second wireless communication module 214, controller 211 receives and analyzing body is implanted into circulation that assembly 1 uploads dissociates RNA signal, afterwards free for circulation RNA information is sent on display 212 and shows, the analysis programme of controller 211 arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, controller 211 sends instruction to described siren 213, siren 213 gives the alarm, notify that wearer notes the danger of cancer return, the control command of controller 211 passes on the reactor 124 in et al. Ke assembly 1 by the second wireless communication module 214, reactor 124 controlled circulation dissociates the unlatching of RNA sensor 11 or resting state, when dissociating 11 dormancy of RNA sensor when circulating, the free RNA sensor of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when the free RNA sensor 11 that circulates is opened, the free RNA sensor 11 of circulation is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, electronegative circulation RNA cause the circulating electrical conductivity of free RNA sensor 11 of dissociating changes, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
Siren 213 is vibrators, notifies that wearer notes the danger of cancer return by the mode of vibration.
The described circulation RNA sensor 11 that dissociates comprises circulation free RNA trapping layer 111, hybridization signal inductive layer 112.Described circulation RNA trapping layer 111 of dissociating is made up of the capture probe with the free RNA specific binding of circulation.Capture probe is peptide nucleic acid(PNA) (PNA).
Hybridization signal inductive layer 112 comprises silicon nanowire array.Hybridization signal inductive layer 112 is on the silicon nanowires utilizing conventional semiconductors technology to process, and is prepared from by silylation modification, surperficial unimolecule rete self assembly operation, fixes to form the free RNA sensor 11 of circulation through capture probe.The preparation process of the free RNA sensor 11 of circulation is well known to those skilled in the art.
First wireless communication module 13, second wireless communication module 214 adopts Bluetooth protocol.
Data receiver 12 can be worn at any part on cancer patient's health, such as, be worn in wrist.
Controller 211 timing realizes the free unlatching of RNA sensor of circulation or the control of dormancy.The interval time of continuously adjustabe between 1s to 1800s that control command is assigned, adjustment stepping is 2s.
Circulation in the present embodiment RNA that dissociates refers to miRNA.
The using method of above-mentioned implanted cancer return real-time monitoring system:
1, control implanted cancer return real-time monitoring system by controller 211 and be in resting state, et al. Ke assembly, with negative electricity (institute is electrically charged atomic weak, can not damage human body), is implanted subcutaneous by the free RNA sensor 11 of now circulation;
2, open implanted cancer return real-time monitoring system by controller 211, make the circulation RNA sensor 11 that dissociates not charged, the RNA that dissociates of the circulation now in tissue fluid can be combined with the free RNA sensor 11 of circulation;
3, after reacting certain hour, close implanted cancer return real-time monitoring system by controller 211 to make it again to be in resting state, the free RNA sensor 11 of now circulation is with negative electricity, the circulation combined with circulation free RNA sensor 11 in tissue fluid RNA and the circulation RNA sensor 11 that dissociates that dissociates is separated, and implanted cancer return real-time monitoring system is that detection is next time ready.
Whether 4, vibrated by dissociate RNA information and siren of the circulation of display on observation display 212, cancer patient knows whether cancer recurs.
Embodiment 2 one kinds of implanted cancer return real-time monitoring systems
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system comprises et al. Ke assembly 1 and external assembly 2, et al. Ke assembly 1 comprises circulation free RNA sensor 11, data processing module 12, first wireless communication module 13, data processing module 12 comprises input interface 121, microprocessor 122, output interface 123, reactor 124, input interface 121 receives electrochemical signals that the free RNA sensor 11 of circulation exports and input microprocessor 122 after it being converted into digital signal, is uploaded to external assembly 2 after microprocessor 122 pairs of digital signals carry out protocol conversion by output interface 123 via the first wireless communication module 13, external assembly 2 comprises data receiver 21, and data receiver 21 comprises controller 211, display 212, siren 213, second wireless communication module 214, controller 211 receives and analyzing body is implanted into circulation that assembly 1 uploads dissociates RNA signal, afterwards free for circulation RNA information is sent on display 212 and shows, the analysis programme of controller 211 arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, controller 211 sends instruction to described siren 213, siren 213 gives the alarm, notify that wearer notes the danger of cancer return, the control command of controller 211 passes on the reactor 124 in et al. Ke assembly 1 by the second wireless communication module 214, reactor 124 controlled circulation dissociates the unlatching of RNA sensor 11 or resting state, when dissociating 11 dormancy of RNA sensor when circulating, the free RNA sensor 11 of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when the free RNA sensor 11 that circulates is opened, the free RNA sensor 11 of circulation is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, electronegative circulation RNA cause the circulating electrical conductivity of free RNA sensor 11 of dissociating changes, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
Siren 213 is luminous organs, notifies that wearer notes the danger of cancer return by the mode of luminescence.
The described circulation RNA sensor 11 that dissociates comprises circulation free RNA trapping layer 111, hybridization signal inductive layer 112.Described circulation RNA trapping layer 111 of dissociating is made up of the capture probe with the free RNA specific binding of circulation.Capture probe is peptide nucleic acid(PNA) (PNA).
Hybridization signal inductive layer 112 comprises silicon nanowire array and forms.Hybridization signal inductive layer 112 is on the silicon nanowires utilizing conventional semiconductors technology to process, and is prepared from by silylation modification, surperficial unimolecule rete self assembly operation, fixes to form the free RNA sensor 11 of circulation through capture probe.The preparation process of the free RNA sensor 11 of circulation is well known to those skilled in the art.
First wireless communication module 13, second wireless communication module 214 adopts Zigbee protocol.
Data receiver 12 uses as in vitro accessory.
Controller 211 timing realizes the free unlatching of RNA sensor 11 of circulation or the control of dormancy.The interval time of continuously adjustabe between 1s to 1800s that control command is assigned, adjustment stepping is 2s.
Circulation in the present embodiment RNA that dissociates refers to circulation free mRNA.
The using method of above-mentioned implanted cancer return real-time monitoring system:
1, control implanted cancer return real-time monitoring system by controller 211 and be in resting state, et al. Ke assembly, with negative electricity (institute is electrically charged atomic weak, can not damage human body), is implanted subcutaneous by the free RNA sensor 11 of now circulation;
2, open implanted cancer return real-time monitoring system by controller 211, make the circulation RNA sensor 11 that dissociates not charged, the RNA that dissociates of the circulation now in tissue fluid can be combined with the free RNA sensor 11 of circulation;
3, after reacting certain hour, close implanted cancer return real-time monitoring system by controller 211 to make it again to be in resting state, the free RNA sensor 11 of now circulation is with negative electricity, the circulation combined with circulation free RNA sensor 11 in tissue fluid RNA and the circulation RNA sensor 11 that dissociates that dissociates is separated, and implanted cancer return real-time monitoring system is that detection is next time ready.
4, by observation display 212 display circulation dissociate RNA information and siren whether luminous, cancer patient knows whether cancer recurs.
Embodiment 3 one kinds of implanted cancer return real-time monitoring systems
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system comprises et al. Ke assembly 1 and external assembly 2, et al. Ke assembly 1 comprises circulation free RNA sensor 11, data processing module 12, first wireless communication module 13, data processing module 12 comprises input interface 121, microprocessor 122, output interface 123, reactor 124, input interface 121 receives electrochemical signals that the free RNA sensor 11 of circulation exports and input microprocessor 122 after it being converted into digital signal, is uploaded to external assembly 2 after microprocessor 122 pairs of digital signals carry out protocol conversion by output interface 123 via the first wireless communication module 13, external assembly 2 comprises data receiver 21, intelligent mobile terminal equipment 22, data receiver 21 comprises controller 211, display 212, siren 213, second wireless communication module 214, the 3rd wireless communication module 215, controller 211 receives and analyzing body is implanted into circulation that assembly 1 uploads dissociates RNA signal, afterwards free for circulation RNA information is sent on display 212 and shows, the analysis programme of controller 211 arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, controller 211 sends instruction to described siren 213, siren 213 gives the alarm, notify that wearer notes the danger of cancer return, the control command of controller 211 passes on the reactor 124 in et al. Ke assembly 1 by the second wireless communication module 214, reactor 124 controlled circulation dissociates the unlatching of RNA sensor 11 or resting state, when dissociating 11 dormancy of RNA sensor when circulating, the free RNA sensor of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when the free RNA sensor 11 that circulates is opened, the free RNA sensor of circulation is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, electronegative circulation RNA cause the circulating electrical conductivity of free RNA sensor of dissociating changes, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
Free for circulation RNA information is sent in intelligent mobile terminal equipment 22 by the 3rd wireless communication module 215 by controller 211.Intelligent mobile terminal equipment 22 carries out remote storage and analysis to the free RNA information of circulation.
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 health, such as wrist.
First wireless communication module 13, second wireless communication module 214, the 3rd wireless communication module 215 adopt Bluetooth protocol.
Siren 213 is vibrators, notifies that wearer notes the danger of cancer return by the mode of vibration.
The free RNA sensor 11 of circulation comprises circulation free RNA trapping layer 111, hybridization signal inductive layer 112.The free RNA trapping layer 111 of circulation is made up of the capture probe with the free RNA specific binding of circulation.Capture probe is peptide nucleic acid(PNA) (PNA).
Hybridization signal inductive layer 112 comprises silicon nanowire array and forms.Hybridization signal inductive layer 112 is on the silicon nanowires utilizing conventional semiconductors technology to process, and is prepared from by silylation modification, surperficial unimolecule rete self assembly operation, fixes to form the free RNA sensor of circulation through capture probe.The preparation process of the free RNA sensor of circulation is well known to those skilled in the art.
Controller 211 timing realizes the free unlatching of RNA sensor of circulation or the control of dormancy.The interval time of continuously adjustabe between 1s to 1800s that control command is assigned, adjustment stepping is 2s.
Circulation in the present embodiment RNA that dissociates refers to circulating tumor miRNA.
The using method of above-mentioned implanted cancer return real-time monitoring system:
1, control implanted cancer return real-time monitoring system by controller 211 and be in resting state, et al. Ke assembly, with negative electricity (institute is electrically charged atomic weak, can not damage human body), is implanted subcutaneous by the free RNA sensor 11 of now circulation;
2, open implanted cancer return real-time monitoring system by controller 211, make the circulation RNA sensor 11 that dissociates not charged, the RNA that dissociates of the circulation now in tissue fluid can be combined with the free RNA sensor 11 of circulation;
3, after reacting certain hour, close implanted cancer return real-time monitoring system by controller 211 to make it again to be in resting state, the free RNA sensor 11 of now circulation is with negative electricity, the circulation combined with circulation free RNA sensor 11 in tissue fluid RNA and the circulation RNA sensor 11 that dissociates that dissociates is separated, and implanted cancer return real-time monitoring system is that detection is next time ready.
Whether 4, vibrated by the dissociate RNA information or intelligent mobile terminal equipment 22 and siren 213 of circulation of display on observation display 212, cancer patient knows whether cancer recurs.
Embodiment 4 one kinds of implanted cancer return real-time monitoring systems
A kind of implanted cancer return real-time monitoring system, cancer return real-time monitoring system comprises et al. Ke assembly 1 and external assembly 2, et al. Ke assembly 1 comprises circulation free RNA sensor 11, data processing module 12, first wireless communication module 13, data processing module 12 comprises input interface 121, microprocessor 122, output interface 123, reactor 124, input interface 121 receives electrochemical signals that the free RNA sensor 11 of circulation exports and input microprocessor 122 after it being converted into digital signal, is uploaded to external assembly 2 after microprocessor 122 pairs of digital signals carry out protocol conversion by output interface 123 via the first wireless communication module 13, external assembly 2 comprises data receiver 21, intelligent mobile terminal equipment 22, data receiver 21 comprises controller 211, display 212, siren 213, second wireless communication module 214, the 3rd wireless communication module 215, controller 211 receives and analyzing body is implanted into circulation that assembly 1 uploads dissociates RNA signal, afterwards free for circulation RNA information is sent on display and shows, the analysis programme of controller 211 arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, controller 211 sends instruction to described siren 213, siren 213 gives the alarm, notify that wearer notes the danger of cancer return, the control command of controller 211 passes on the reactor 124 in et al. Ke assembly 1 by the second wireless communication module 214, reactor 124 controlled circulation dissociates the unlatching of RNA sensor 11 or resting state, when dissociating 11 dormancy of RNA sensor when circulating, the free RNA sensor of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when the free RNA sensor 11 that circulates is opened, the free RNA sensor of circulation is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, electronegative circulation RNA cause the circulating electrical conductivity of free RNA sensor of dissociating changes, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
Free for circulation RNA information is sent in intelligent mobile terminal equipment 22 by the 3rd wireless communication module 215 by controller 211.Intelligent mobile terminal equipment 22 carries out remote storage and analysis to the free RNA information of circulation.
Intelligent terminal 22 can be smart mobile phone, flat board or computer.
Data receiver 12 uses as in vitro accessory.
First wireless communication module 13, second wireless communication module 214, the 3rd wireless communication module 215 adopt Zigbee protocol.
Siren 213 is luminous organs, notifies that wearer notes the danger of cancer return by the mode of luminescence.
The free RNA sensor 11 of circulation comprises circulation free RNA trapping layer 111, hybridization signal inductive layer 112.The free RNA trapping layer 111 of circulation is made up of the capture probe with the free RNA specific binding of circulation.Capture probe is peptide nucleic acid(PNA) (PNA).
Hybridization signal inductive layer 112 comprises silicon nanowire array.Hybridization signal inductive layer 112 is on the silicon nanowires utilizing conventional semiconductors technology to process, and is prepared from by silylation modification, surperficial unimolecule rete self assembly operation, fixes to form the free RNA sensor 11 of circulation through capture probe.The preparation process of the free RNA sensor 11 of circulation is well known to those skilled in the art.
Controller 211 timing realizes the free unlatching of RNA sensor 11 of circulation or the control of dormancy.The interval time of continuously adjustabe between 1s to 1800s that control command is assigned, adjustment stepping is 2s.
Circulation in the present embodiment RNA that dissociates refers to circulation free mRNA.
The using method of above-mentioned implanted cancer return real-time monitoring system:
1, control implanted cancer return real-time monitoring system by controller 211 and be in resting state, et al. Ke assembly, with negative electricity (institute is electrically charged atomic weak, can not damage human body), is implanted subcutaneous by the free RNA sensor 11 of now circulation;
2, open implanted cancer return real-time monitoring system by controller 211, make the circulation RNA sensor 11 that dissociates not charged, the RNA that dissociates of the circulation now in tissue fluid can be combined with the free RNA sensor 11 of circulation;
3, after reacting certain hour, close implanted cancer return real-time monitoring system by controller 211 to make it again to be in resting state, the free RNA sensor 11 of now circulation is with negative electricity, the circulation combined with circulation free RNA sensor 11 in tissue fluid RNA and the circulation RNA sensor 11 that dissociates that dissociates is separated, and implanted cancer return real-time monitoring system is that detection is next time ready.
Whether 4, luminous by the dissociate RNA information or intelligent mobile terminal equipment 22 and siren 213 of circulation of display on observation display 212, cancer patient knows whether cancer recurs.
Although illustrate and describe embodiments of the invention, those having ordinary skill in the art will appreciate that: can carry out multiple change, amendment, replacement and modification to these embodiments when not departing from principle of the present invention and aim, scope of the present invention is by claim and equivalents thereof.

Claims (9)

1. an implanted cancer return real-time monitoring system, is characterized in that, described monitoring system comprises et al. Ke assembly (1) and external assembly (2), described et al. Ke assembly (1) comprises circulation free RNA sensor (11), data processing module (12), the first wireless communication module (13), described data processing module (12) comprises input interface (121), microprocessor (122), output interface (123), reactor (124), described input interface (121) receives described circulation and to dissociate electrochemical signals that RNA sensor (11) exports input described microprocessor (122) after it is converted into digital signal, is uploaded to described external assembly (2) after described microprocessor (122) carries out protocol conversion to digital signal by described output interface (123) via described first wireless communication module (13), described external assembly (2) comprises data receiver (21), and described data receiver (21) comprises controller (211), display (212), siren (213), the second wireless communication module (214), described controller (211) receives and analyzes circulation that described et al. Ke assembly (1) uploads and to dissociate RNA signal, afterwards free for circulation RNA information is sent to the upper display of described display (212), the analysis programme of described controller (211) arranges a threshold value, when this threshold value of horizontal exceeding of the free RNA that circulates, described controller (211) sends instruction to described siren (213), described siren (213) gives the alarm, notify that wearer notes the danger of cancer return, the control command of described controller (211) passes on the described reactor (124) in described et al. Ke assembly (1) by described second wireless communication module (214), control described circulation to dissociate the unlatching of RNA sensor (11) or resting state, when described circulation dissociates RNA sensor (11) dormancy, the free RNA sensor (11) of circulation is with negative electricity, association reaction is there is not with the RNA that dissociates of the circulation with negative electricity, when described circulation dissociates RNA sensor (11) unlatching, the described circulation RNA sensor (11) that dissociates is not charged, association reaction is there is with the RNA that dissociates of the circulation with negative electricity, the electronegative circulation RNA that dissociates causes the dissociate electrical conductivity of RNA sensor (11) of described circulation to change, thus the concentration information of free for circulation RNA is converted into electrochemical signals.
2. monitoring system according to claim 1, it is characterized in that, described external assembly (2) also comprises intelligent mobile terminal equipment (22), described data receiver (21) also comprises the 3rd wireless communication module (215), and free for circulation RNA information is sent in described intelligent mobile terminal equipment (22) by described 3rd wireless communication module (215) by described controller (211).
3. monitoring system according to claim 1 and 2, is characterized in that, described siren (213) is vibrator, notifies that wearer notes the danger of cancer return by the mode of vibration.
4. monitoring system according to claim 1 and 2, is characterized in that, described siren (213) is luminous organ, notifies that wearer notes the danger of cancer return by the mode of luminescence.
5. monitoring system according to claim 1 and 2, is characterized in that, the described circulation RNA sensor (11) that dissociates comprises circulation free RNA trapping layer (111), hybridization signal inductive layer (112); Described circulation RNA trapping layer (111) of dissociating sticks on described hybridization signal inductive layer (112).
6. monitoring system according to claim 5, is characterized in that, described circulation RNA trapping layer (111) of dissociating is made up of the capture probe with the free RNA specific binding of circulation.
7. monitoring system according to claim 6, is characterized in that, described capture probe is peptide nucleic acid(PNA).
8. monitoring system according to claim 5, is characterized in that, described hybridization signal inductive layer (112) comprises silicon nanowire array.
9. monitoring system according to claim 1 and 2, it is characterized in that, described first wireless communication module (13), described second wireless communication module (214), described 3rd wireless communication module (215) adopt in Bluetooth protocol or Zigbee protocol any one.
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