CN103877645A - Detection control device for anesthetics in blood - Google Patents
Detection control device for anesthetics in blood Download PDFInfo
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- CN103877645A CN103877645A CN201210563274.2A CN201210563274A CN103877645A CN 103877645 A CN103877645 A CN 103877645A CN 201210563274 A CN201210563274 A CN 201210563274A CN 103877645 A CN103877645 A CN 103877645A
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Abstract
The invention discloses a detection control device for anesthetics in blood. The detection control device comprises an anesthetic patient blood receiver (BR). Detection limit and qualitative and quantitative analytical concentration of the blood are detected, analyzed and acquired by the aid of an ion mobility spectrometry (IMS) system or a mass spectrometry (MS) system or an ion mobility spectrometry and mass spectrometry (IMS-MS) combination system, so that the requirement of the human blood on an administration concentration analysis range can be met, and an analytical method for quickly detecting the anesthetics in the blood can be created; analysis results are accurately displayed via a computer software system and include pharmacokinetic models and parameters relevant to medicine infusion; a medical target control infusion (TCI) system can be directly guided by the output results, and hardware of the medical target control infusion system comprises medical infusion pumps, a personal computer (PC) and a safety system mechanism, the infusion pumps can run under the control of the personal computer, and the personal computer can be switched off by the safety system mechanism when the errors occur. The detection control device has the advantages that the detection control device can be used easily and conveniently, is speedy, is high in efficiency and good in reliability, can be automatically controlled, can be widely applied to clinical administration depth analysis and can be used for guiding doctors to accurately apply medicine to the blood in an online manner.
Description
Technical field
The invention discloses narcotic detection control apparatus in a kind of blood, this detection control apparatus comprises: the blood receptor (BR) of anaesthesia patient; This blood is detected to analyze to obtain by ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) measures detectability and quantitative analysis concentration to meet blood of human body administration concentration analyst coverage, has set up narcotic analytical method in fast detecting blood; Analysis result accurately shows by microcomputer software system simultaneously, comprises the parameter that pharmacokinetic model and infusion of drug are relevant; This Output rusults directly instructs medical target-controlled infusion system (TCI), and its hardware comprises medical infusion pump, controls the microcomputer (PC) of infusion pump running and the security system mechanism of closing in the time that microcomputer makes a mistake; This checkout gear is easy to use, quick, efficient, good reliability, can realize automatization and control, and can be widely used in clinical administration depth analysis, instructs online, the accurate medication of doctor.
Background technology
Blood is to be flowing in heart and endovascular opaque red liquid, and main component is blood plasma, hemocyte.Belong to connective tissue, i.e. layer of structure in biosystem.In blood, contain various nutritional labelings, as inorganic salt, oxygen and products of cellular metabolism, hormone, enzyme and antibody etc., the effect of nutritious tissue, adjusting organ activity and defence harmful substance.
For many years, scientists is being studied side effects from the use of anesthetics always, great majority also rest on zoopery and cell culture stage, aspect the impact of human health, be difficult to draw sure conclusion at anaesthetic, but zero scattered loose experimental result shows that anaesthetic can produce harmful effect to human health really, such as the experiment having show to use the anesthesia of patient over administration of general anesthesia easy the neuratrophia diseases such as parkinson disease, the neuron of cell culture is exposed to very short time in the anesthetics such as chloroform, will cause the abnormal responses such as protein coagulation, and protein coagulation meeting increases the generation of neuratrophia disease.Also have experiment show, anaesthetic can damage immune system, the anaesthetic in body can be induced the Apoptoais in leukocyte.U.S. FDA sends up-to-date warning: use anesthetic agents excessive in side effect fatal generation.These products contained medicines, as lignocaine, tetracaine, benzocaine and prilocaine, has prescription drugs, also has nonprescription drugs.Fentanyl is the potent narcosis analgesic of nineteen sixty synthetic, is widely used in various surgical operations, especially operation on vessels of heart.If, in whole instillation human bodies, during extracorporeal circulation and thereafter, blood plasma fentanyl concentration is lower than analgesia/anesthetic concentration before the fentanyl of scheduled volume is circulated in vitro, there is increased heart rate in patient, hypertension, myocardial ischemia increases, and even patient is clear-headed, the untoward reaction such as autonomic reflex enhancing.
In a word, after patient injection anesthetics, if anesthesia medication is crossed shallow meeting and caused patient's conscious mind, can feel the misery that operation brings.In patient body, produce very high anesthetics blood drug level, may cause irregular heartbeats, epilepsy, and stupor, even dead.And the judgement of clinical medicine depth of anesthesia only relies on medication experience for many years, it is accurate that the impact that human body difference is brought is difficult to medication.Therefore, instruct anaesthetist's clinical application amount, detecting depth of anesthesia has become the problem that needs solution too impatient to wait.
For avoiding the complications in anaesthesia process, at the beginning of the 70-80 age, adopt radioimmunology (RIA) and gas chromatography (GC) to measure blood plasma fentanyl concentration.But GC measures quite difficulty, and RIA method lacks selectivity, and acquisition medicine box is also had any problem.Within 1988, start to inquire into employing high performance liquid chromatography (HPLC), so far also in use, but result accuracy is very poor.
Ion mobility spectrometry (Ion Mobility Spectrometry, IMS) technology is a kind of separation detection technology that 20 century 70s occur, compared with traditional mass spectrum, chromatographic apparatus, have simple in structure, highly sensitive, analysis speed is fast, the feature of reliable results.Ion mobility spectrometry is mainly made up of chamber, ion gate, drift region and detector.Sample gas produces molecule, ion in chamber ionization.The ion gate that ion is opened by periodicity under the ordering about of electric field enters drift region.With the neutral drift gas molecule of adverse current constantly in the process of collision, due to these ions migration rate difference separately in electric field, different ions is separated, successively arrive collector detected.Therefore just can determine the existence of evaluating objects material by migration time, and application peak area or peak height can be determined the concentration of respective substance.Can in atmospheric environment, detect trace substance, be suitable for on-the-spot use.We IMS of research has been widely used in the fields such as chemical warfare agent, drugs, explosive detection, environmental monitoring, monitoring poisonous gas, fire monitoring, water pollution monitoring and food inspection at present.
Mass spectrum (MS) is the collection of illustrative plates that charge atom, molecule or molecular fragment are arranged by the size order of charge-mass ratio (or quality).Mass spectrograph is that a class can make material particle change into ion and by suitable electric field, magnetic field, whether they be realized to mass-to-charge ratio separation by locus, time order and function or orbitally stable, and after detected intensity, carries out the instrument of species analysis.Mass spectrograph is mainly made up of analytical system, electricity system and vacuum system.Become to have molecule, ion or the fragment ion of different quality in ionization source ionization for the sample molecule (or atom) of analyzing, these single charge ions obtain identical kinetic energy and form a beam ion in accelerating field, enter the analyzer being formed by Electric and magnetic fields, ion beam medium velocity is large by power plant's post deflection compared with slow ion, and fireballing deflection is little; In the deflection on the contrary of magnetic field intermediate ion generation angular velocity vector, i.e. still deflection of slow-footed ion is large, and fireballing deflection is little; In the time that the deflecting action of two fields compensates one another, their track intersects at a point.Meanwhile, in magnetic field, can also there is the separation of quality, so just make to there is same mass-to-charge ratio and the different ion focusing of speed in same point, the ion focusing of different mass-to-charge ratioes is on difference, its focal plane is close to plane, detect and can obtain different spectral lines, i.e. mass spectrum by detection control system herein.By mass spectral analysis, can obtain many-sided information such as isotopic composition and molecular structure in the molecular weight, molecular formula, molecule of analytic sample.
Summary of the invention
According to the deficiency of existing detection technique, the object of the invention is to set up narcotic detection control apparatus in a kind of new blood.
In a kind of blood, narcotic detection control apparatus comprises blood receptor (BR), ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), the microcomputer (PC) of medical target-controlled infusion system (TCI) and the running of control infusion pump;
Blood receptor (BR) comprises two interfaces, and an interface is by rubber seal, and this interface can insert sampling probe and inject anticoagulant; Second interface is anesthesia blood entrance and exit, and second interface is connected with the injection port of mass spectrometry system (IMS-MS) with ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry; Blood in receptor can directly send into ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) detects analysis;
Ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry are connected with microcomputer (PC) signal with mass spectrometry system (IMS-MS), and ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) detect analytical data result and export in microcomputer (PC); Microcomputer (PC) is connected with medical target-controlled infusion system (TCI) signal, by microcomputer (PC) and medical target-controlled infusion system (TCI) action.
Medical target-controlled infusion system (TCI) comprises medical infusion pump, controls the microcomputer (PC) of medical infusion pump running.
Anaesthesia patient blood in this receptor is detected and is analyzed by ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), obtains qualitative and quantitative analysis concentration results; Analysis result accurately shows by microcomputer software system simultaneously, comprises pharmacokinetic model and the relevant parameter model of infusion of drug of a large amount of clinical experiment data fittings; This Output rusults is directly instructed medical infusion pump in medical target-controlled infusion system (TCI), is controlled infusion pump running by microcomputer (PC).
Described ion mobility spectrometry (IMS) can be by positive and negative different high-voltage power supplies, and the single or array ion migration being made up of nickel source, uviol lamp, electron spray or corona discharge ionization source is composed;
Source of the gas (air) in ion mobility spectrometry instrument, first by membrane filtration dewater, again by cleanser (silica gel, molecular sieve, active carbon) dewater successively, dedusting, organic matter removal.Clean gas, after humidity sensor, pressure transducer, effusion meter control, then is divided into respectively coutroi velocity of two-way by T-shaped threeway.Wherein carrier gas is done on a road, and a road is done and floated gas.Carrier gas and float letter shoot route four fluorine tube and metal tube composition.
IMS detects in control system, can add chemical addition agent in carrier gas (air) or in floating gas (air) gas circuit.As one or two or more kinds mixing in acetone, butanone, methanol, dichloromethane, chloroform, carbon tetrachloride.
Described mass spectrum (MS) can be one or more in uviol lamp ionization source (UVU), dielectric barrier discharge ionization source (DBD), electron impact ionization source (EI), chemical ionization source (CI), fast atom bombardment ionization source (FAB), field desorption ionization source (FD), electron spray ionisation source (ESI), Atmosphere Pressure Chemical Ionization (APCI) source (APCI).
It can be that motor injector, motor injector and film device sampling system are analysed in pyrolysis that injector is analysed in the pyrolysis that ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) adopt, and sample pyrolysis eutectoid temperature is from room temperature to 300 DEG C.
Analyse the motor injector device of sample introduction for pyrolysis, it analyses room module by pyrolysis and motor actuating device module two parts form, wherein electrothermal Resolution Room module comprises calandria and temperature control sensor, carrier gas supply and sampling device, the elementary heat-preservation fixing device of hot Resolution Room and the final attemperator of hot Resolution Room, motor actuating device module comprises: accurate two-way transmission mechanism, can ensure that hot Resolution Room accurately and steadily opens and closes; Sensor localization and control system, can realize the accurate control of rising and declining with hot Resolution Room component.The parts rising that the control of motor actuating device coordinates with hot Resolution Room and decline realize the opening and closing of hot Resolution Room.
When sample test, the sample introduction sheet of wiping being crossed to sample is put on the insulation retaining element of hot Resolution Room part, then controls top by step motor control system and accurately rises reposefully, and realize sealing with hot Resolution Room.The sample that final carrier gas is carried after pyrolysis is analysed enters detector.
Described blood receptor can adopt batch (-type) blood sampling for patient, according to administration concentration change interval, batch (-type) blood sampling time interval is set, and in blood sample input instrument sampling device, carries out automatic analysis.
Described ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry (IMS-MS) detection control apparatus, can realize and in operating room, carry out in situ detection; Directly to enter the injector that detects control system containing a kind of mode of blood of anesthetic agents, another kind of mode is that the blood that contains anesthetic agents is carried out to simple solvent extraction, and the injector that the medicine of extraction enters detection control system again carries out hot analytical analysis.
Ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) can directly manually sample and sample introduction, and sampling volume is 1-50 μ L, or the automatic sampling mode of infrared location, Electric Machine Control;
Can be tetrafluoro sheet, stainless steel substrates, graphite flake, piezoid, sheet glass, metallic iron or aluminium flake for the carrier that carries blood; Sample introduction sheet thickness is less than pyrolysis and analyses injector injection port height; Sampling place be taking 0.5-1.2cm as radius, the degree of depth is the circular hole of 0.5-3mm; This circular hole bottom is for coarse surface or fill disposable network structure small pieces (polytetrafluoroethylmaterial material) at circular hole place, makes blood or plasma sample be laid in sampling place surface, increases and carrier gas contact area, is more conducive to carrier gas thermal purging.
Ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) can be added chemical addition agent in carrier gas (air) or in floating gas (air) gas circuit, and chemical addition agent is one or more in acetone, butanone, methanol, dichloromethane, chloroform, carbon tetrachloride.
Described ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), can carry out quantitative and semi-quantitative analysis to patient's blood drug level accurately; Click simultaneously " spectrogram adds up " function is manually set " terminal pattern data acquisition add up spectrogram number " and " terminal lower curve number " in software workstation IMS software; Can realize that multiple spectrogram continuous acquisition, signal add and, improve detection sensitivity; Simultaneously determine different narcotic quantitative analysis concentration ranges according to the blood drug level scope of clinical use, can automatically generate graticule equation, data variation coefficient is less than 20%.
Described detection control apparatus, the anesthetis that can be used for analyzing and testing has enflurane, isoflurane, Sevoflurane, nitrous oxide (also claiming " laughing gas "), halothane, desflurane, methoxiflurane, ether, xenon, penthiobarbital, magnesium rope than appropriate, thiomethibumallum, propofol, ketamine, etomidate, sodium oxybate, procaine, chloroprocaine, tetracaine, cocaine, benzocaine, lignocaine, bupivacaine, levobupivacaine, ropivacaine.
Microcomputer (PC) can be analyzed for the individual pharmacokinetics parameter of anesthetis constant bit rate transmission, narcotic biological half-life, narcotic apparent volume of distribution, narcotic clearance rate, narcotic blood drug level-time relationship, narcotic bioavailability, and sets up appropriate model;
The testing result of microcomputer (PC) can be fed back human body by TCI infusion system as patient informations such as degree of flaccid muscles, heart rate, blood pressures the real time reaction of medicine in time; Microcomputer (PC) can change in time according to the detection medical target-controlled infusion system of information control (TCI) the infusion efficiency of medicine.
In medical target-controlled infusion system, medical infusion pump comprises 5-10 the array medical injection pump using in parallel; Described medical infusion pump comprises controller, executor, pump core and the storage medicinal liquid device being connected with pump core input channel, and the opposite side being connected with pump core input channel is sampling probe.
Different array medical injection pumping systems can be respectively to one or two or more kinds while in muscle relaxant, tranquilizer, analgesic, local anesthetic and other classification medicines or according to the successively administration of administration mechanism.
At present, medically Anesthesia becomes the nightmare that Chinese can't get rid of already in the heart.The successful exploitation of this detection control system will be used for making up backwardness and the gap of China's medical circle anesthetis context of detection, rewrites the new anesthesia history in the whole world.
Advantage of the present invention is as follows:
1. ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry (IMS-MS) detection control apparatus described in invention, detecting instrument can be realized and in operating room, carry out in situ detection;
2. ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry checkout gear (IMS-MS) described in, can adopt batch (-type) blood sampling or continous way blood sampling pattern for patient, realize in automatic blood sampling input sampling device after continuous blood sampling time or batch (-type) blood sampling time interval are set.
3. the detection control apparatus in the present invention can be analyzed for individual pharmacokinetics parameters such as anesthetis constant bit rate transmission, narcotic biological half-life, narcotic apparent volume of distribution, narcotic clearance rate, narcotic blood drug level-time relationship, narcotic bioavailability, and sets up appropriate kinetic model.
Brief description of the drawings
Fig. 1 is the associated diagram of narcotic detection control apparatus ingredient in blood;
Fig. 2 is the structural representation of anaesthetizing blood receptor in detection control apparatus;
Fig. 3 is the structural representation that detects control system intermediate ion migration spectrum;
Fig. 4 is for detecting mass spectrographic structural representation in control system;
Fig. 5 detects the circulation schematic diagram of gas circuit that in control system, IMS uses;
Fig. 6 detects the motor pyrolysis that in control system, IMS uses to analyse injector schematic diagram;
Fig. 7 detects the sample introduction sheet pictorial diagram that in control system, IMS uses;
Fig. 8 arranges interface schematic diagram for detecting in control system PC data continuous acquisition pattern in IMS;
Fig. 9 arranges interface schematic diagram for detecting IMS qualitative and quantitative analysis pattern in control system;
Figure 10 is the background signal ion migration spectrogram (RIP) of ion mobility spectrometry under negative ion mode;
Figure 11 is the ion migration spectrogram that under negative ion mode, ion mobility spectrometry detects 10 μ L blood blank;
Figure 12 is that under negative ion mode, ion mobility spectrometry detects 10 μ L, moves spectrogram containing the blood ion of 1ppm propofol agent;
Figure 13 is that under negative ion mode, ion mobility spectrometry detects 10 μ L, moves spectrogram containing the blood ion of 5ppm propofol agent;
Figure 14 is that under negative ion mode, ion mobility spectrometry detects 10 μ L, moves spectrogram containing the blood ion of 10ppm propofol agent;
Figure 15 is that under negative ion mode, ion mobility spectrometry detects 10 μ L, moves spectrogram containing the blood ion of 20ppm propofol agent;
Figure 16 be under negative ion mode ion mobility spectrometry detect 10 μ L, containing the blood of 0.5-20ppm propofol agent, the canonical plotting of signal intensity and blood drug level;
Detailed description of the invention
In blood, narcotic detection composition of the control system partial association illustrates as shown in Figure 1: 1BR is anaesthesia patient blood receptor; 2IMS is ion mobility spectrometry, 2 to 3 expression ion mobility spectrometries and mass spectrometry system; 3MS is mass spectrum; 4PC controls microcomputer and the terminal kinetic parameter output system of infusion pump running.5TCI is target-controlled infusion system;
In detection control apparatus, anaesthetize the structural representation of blood receptor as shown in Figure 2: 6 connect entry needle, anticoagulant inlet 7, overcoat 8, piston 9, sealing ring 10, core bar 11, by hands 12;
Detect the structural representation of control system intermediate ion migration spectrum as shown in Figure 3, mainly comprise following components: sample introduction sheet 13, injector 14, carrier gas 15, ionized region 16, migration area 17, ion source 18, gas outlet 19, ion gate 20, migration ring 21, aperture plate 22, float gas 23, detector 24.Sampling device is mainly analysed injector, sample introduction sheet and carrier gas transfer pipeline by pyrolysis and is formed, and wherein electrothermal parsing injector is mainly made up of injection port, heating rod and temperature controller.
In detection control system, mass spectrographic structural representation as shown in Figure 4: molecular pump 25, pore electrode 26, focusing electrode 27, heated capillary injection port 28, transmission electrode 29, molecular pump 30, DC source 31, current-limiting resistance 32, UVU lamp 33.
Detect the circulation schematic diagram of gas circuit of IMS use in control system as shown in Figure 5: primary filter 34, diaphragm pump 35, cleanser I is 36, cleanser II is 37, filter 38, humidity sensor 39, T-shaped threeway 40, flow regulating valve I is 41, flow regulating valve II is 42, transference tube 43, injector 44.Source of the gas in ion mobility spectrometry instrument is selected air, nitrogen or other noble gases, first by membrane filtration dewater, again after humidity sensor, pressure transducer, effusion meter control, then by cleanser (silica gel, molecular sieve, active carbon) dewater successively, dedusting, organic matter removal.Clean gas after purification is divided into two-way coutroi velocity respectively by T-shaped threeway again, and wherein carrier gas is done on a road, and another road is done and floated gas.Carrier gas and float the clean four fluorine tube of letter shoot route and metal tube composition.
Detect the motor pyrolysis that in control system, IMS uses and analyse injector schematic diagram as shown in Figure 6: thermal insulation cover 45, hot Resolution Room fixture I 46, hot Resolution Room insulation fixture I 47, hot Resolution Room insulation fixture II 48, hot Resolution Room 49, hot Resolution Room fixture II 50, top 51, connecting plate 52, linear bearing 53, Linear transmission parts I 54, Linear transmission parts II 55, shaft coupling 56, electric machine support 57, motor 58, sensor localization pin 59, photoelectric sensor 60, step motor control plate 61.Wherein, 45-50 is that part is analysed in pyrolysis, and the fixing and heat insulation module of hot Resolution Room is worked; 51-61 is drive mechanism, analyses and the function of sample introduction by the accurate control of motor being realized to sampling, the pyrolysis of injector.Because the temperature in hot Resolution Room is very high, can make the sample in the middle of being placed in vaporize rapidly, the resolved indoor carrier gas air-flow of sample of vaporization takes in detector.
Detect the sample introduction sheet pictorial diagram of IMS use in control system as shown in Figure 7: can be tetrafluoro sheet, stainless steel substrates, graphite flake, piezoid, sheet glass, metallic iron or aluminium flake for carrying the carrier of blood sample.Sample introduction sheet thickness is less than pyrolysis and analyses injector injection port height; Sampling place be taking 0.5-1.2cm as radius, the degree of depth is the circular hole of 0.5-3mm.This circular hole bottom is for coarse surface or fill disposable network structure small pieces (polytetrafluoroethylmaterial material or metallic iron, aluminum) at circular hole place, make blood or plasma sample be laid in sampling place surface, increase and carrier gas contact area, be more conducive to carrier gas thermal purging.
In workstation software detection control system, in IMS, PC data continuous acquisition pattern arranges interface schematic diagram as shown in Figure 8: under debugging interface, manually rewrite " terminal pattern data acquisition add up spectrogram number " and " terminal lower curve number ", click " determining ", be respectively 3 and 15 as Fig. 8 shows, click " determining ".Realize and adding and function as need, click and choose " cumulative spectrogram ", then click " determining ".This function can realize that multiple spectrogram continuous acquisition, signal add and, improve detection sensitivity.
The IMS qualitative and quantitative analysis pattern in control system that detects arranges interface schematic diagram as shown in Figure 9: under software debugging interface, manually rewrite the coefficient data of " detected peaks 1,2,3 " migration time scope and linear graticule equation, click " setting " and can realize qualitative and quantitative analysis function.Automatic mode can be set, automatically generate graticule equation and realize test automatically simultaneously.
Figure 10-16 provided some experiment spectrograms to intermediate ion of the present invention migration spectrum detect in blood propofol to explanation.The experiment condition of these spectrograms is: when experiment, migration tube temperature remains on 100 DEG C, 180 DEG C of injector temperature, and floating gas (air), carrier gas (air) air-flow is respectively 400mL/min, 600mL/min, it is motor injector that injector is analysed in pyrolysis.
Embodiment 1
Propofol agent sample obtains desirable detection signal at negative ion mode, and the ion mobility spectrometry fast detector that experiment is used is under test operation condition, and air reagent ion peak appears at about 5ms(as Figure 10).
Get the blood sample of 1-50 μ L with microsyringe in sampling place of sample introduction sheet.Under negative ion mode, taking ionic migration spectrometer as detecting instrument, carrier gas is carried blood sample steam after pyrolysis is analysed and is entered ion migration spectrometer and carry out analyzing and testing, disturbs propofol agent to detect, as shown in figure 11 at 8.3ms place without obvious background signal.Blood blank background signal, on average about 45mv of 8.3ms, can be set to background threshold value, for background correction signal.
Qualitative analysis test: get 1-50 μ L with microsyringe, contain the narcotic blood sample solution of 0.5-20ppm in sampling place of sample introduction sheet.Under negative ion mode, taking ionic migration spectrometer as detecting instrument, carrier gas is carried anesthetis sample steam after pyrolysis is analysed and is entered ion migration spectrometer and carry out analyzing and testing; Experiment is taking the blood sample containing propofol agent as example, and the ion migration spectrometer of use is under test operation condition, and propofol agent sample signal peak migration time is at about 8.3ms.1ppm, 5ppm, 10ppm, the medicinal the inventive method analysis of 20ppm blood adds and average signal (not background correction signal) is followed successively by 100mv, 325mv, 526mv, 1120mv(as shown in Figure 12-15).
Quantitative analysis test: get blood sample and make solvent, by anesthetis diluted sample (being followed successively by 20ppm, 15ppm, 10ppm, 5ppm, 2.5ppm, 1ppm, 0.5ppm as propofol injection diluted to compound concentration).Get equal-volume sample 1-50 μ L with microsyringe, 0.5-20ppm contains narcotic blood sample solution in sampling place of sample introduction sheet, directly be sent to the pyrolysis of ion mobility spectrometry fast detector and analyse and in injector, carry out pyrolysis and analyse, carry sample by carrier gas and enter transference tube and analyze and obtain anesthetis detection signal.Record corresponding signal peak signal intensity (background correction signal), set up the linear relation between blood drug level (0.5-20ppm) and signal intensity.Graticule equation is y=53.556x+2.6629, and correlation coefficient is greater than 99%.Apply this relational expression and do repeated confirmatory experiment, the coefficient of variation that under the same terms, sample repeats is less than 20%.The foundation of this relational expression, can better instruct the analysis of the clinical medicine patient administration degree of depth, instructs medical injection pumping system.In addition, medically clinical administration concentration is generally between 1-6ppm, and graticule equation meets clinical practice demand (as shown in figure 16).
Claims (13)
1. narcotic detection control apparatus in a blood, it is characterized in that: comprise blood receptor (BR), ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), the microcomputer (PC) of medical target-controlled infusion system (TCI) and the running of control infusion pump;
Blood receptor (BR) comprises two interfaces, and an interface is by rubber seal, and this interface can insert sampling probe and inject anticoagulant; Second interface is anesthesia blood entrance and exit, and second interface is connected with the injection port of mass spectrometry system (IMS-MS) with ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry; Blood in receptor can directly send into ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) detects analysis;
Ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry are connected with microcomputer (PC) signal with mass spectrometry system (IMS-MS), and ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) detect analytical data result and export in microcomputer (PC); Microcomputer (PC) is connected with medical target-controlled infusion system (TCI) signal, by microcomputer (PC) and medical target-controlled infusion system (TCI) action.
2. detection control apparatus according to claim 1, is characterized in that: medical target-controlled infusion system (TCI) comprises medical infusion pump, controls the microcomputer (PC) of medical infusion pump running.
3. detection control apparatus according to claim 1, it is characterized in that: the anaesthesia patient blood in this receptor is detected and analyzed by ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), obtains qualitative and quantitative analysis concentration results; Analysis result accurately shows by microcomputer software system simultaneously, comprises pharmacokinetic model and the relevant parameter model of infusion of drug of a large amount of clinical experiment data fittings; This Output rusults directly instructs the medical infusion pump in medical target-controlled infusion system (TCI) to control infusion pump running by microcomputer (PC).
4. detection control apparatus according to claim 1, it is characterized in that: described ion mobility spectrometry (IMS) can be by positive and negative different high-voltage power supplies, and the single or array ion migration being made up of nickel source, uviol lamp, electron spray or corona discharge ionization source is composed;
Described mass spectrum (MS) ionization source can be one or more in uviol lamp ionization source (UVU), dielectric barrier discharge ionization source (DBD), electron impact ionization source (EI), chemical ionization source (CI), fast atom bombardment ionization source (FAB), field desorption ionization source (FD), electron spray ionisation source (ESI), Atmosphere Pressure Chemical Ionization (APCI) source (APCI);
It can be that motor injector, motor injector and film device sampling system are analysed in pyrolysis that injector is analysed in the pyrolysis that ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) adopt, and sample pyrolysis eutectoid temperature is from room temperature to 300 DEG C.
5. detection control apparatus according to claim 1, it is characterized in that: described blood receptor can adopt batch (-type) blood sampling for patient, according to administration concentration change interval, batch (-type) blood sampling time interval is set, in blood sample input instrument sampling device, carries out automatic analysis.
6. detection control apparatus according to claim 1, is characterized in that: described ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry (IMS-MS) detect control system, can realize and in operating room, carry out in situ detection; Directly to enter the injector that detects control system containing a kind of mode of blood of anesthetic agents, another kind of mode is that the blood that contains anesthetic agents is carried out to simple solvent extraction, and the injector that the medicine of extraction enters detection control system again carries out hot analytical analysis.
7. detection control apparatus according to claim 1, it is characterized in that: ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) can directly manually sample and sample introduction, sampling volume is 1-50 μ L, or the automatic sampling mode of infrared location, Electric Machine Control;
Can be tetrafluoro sheet, stainless steel substrates, graphite flake, piezoid, sheet glass, metallic iron or aluminium flake for the carrier that carries blood; Sample introduction sheet thickness is less than pyrolysis and analyses injector injection port height; Sampling place be taking 0.5-1.2cm as radius, the degree of depth is the circular hole of 0.5-3mm; This circular hole bottom is for coarse surface or fill disposable network structure small pieces (polytetrafluoroethylmaterial material) at circular hole place, makes blood or plasma sample be laid in sampling place surface, increases and carrier gas contact area, is more conducive to carrier gas thermal purging.
8. detection control apparatus according to claim 1, it is characterized in that: ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS) can be added chemical addition agent in carrier gas or in floating gas gas circuit, and chemical addition agent is one or more in acetone, butanone, methanol, dichloromethane, chloroform, carbon tetrachloride.
9. detection control apparatus according to claim 1, it is characterized in that: described ion mobility spectrometry (IMS), mass spectrum (MS) or ion mobility spectrometry and mass spectrometry system (IMS-MS), can carry out quantitative and semi-quantitative analysis to patient's blood drug level accurately; Click simultaneously " spectrogram adds up " function is manually set " terminal pattern data acquisition add up spectrogram number " and " terminal lower curve number " in software workstation IMS software; Can realize that multiple spectrogram continuous acquisition, signal add and, improve detection sensitivity; Simultaneously determine different narcotic quantitative analysis concentration ranges according to the blood drug level scope of clinical use, can automatically generate graticule equation, data variation coefficient is less than 20%.
10. detection control apparatus according to claim 1, is characterized in that: the anesthetis that can be used for analyzing and testing has enflurane, isoflurane, Sevoflurane, nitrous oxide, halothane, desflurane, methoxiflurane, ether, xenon, penthiobarbital, magnesium rope than appropriate, thiomethibumallum, propofol, ketamine, etomidate, sodium oxybate, procaine, chloroprocaine, tetracaine, cocaine, benzocaine, lignocaine, bupivacaine, levobupivacaine, ropivacaine.
11. detection control apparatus according to claim 1, it is characterized in that: microcomputer (PC) can be analyzed for the individual pharmacokinetics parameter of anesthetis constant bit rate transmission, narcotic biological half-life, narcotic apparent volume of distribution, narcotic clearance rate, narcotic blood drug level-time relationship, narcotic bioavailability, and sets up appropriate model;
The testing result of microcomputer (PC) can be fed back human body by TCI infusion system as patient informations such as degree of flaccid muscles, heart rate, blood pressures the real time reaction of medicine in time; Microcomputer (PC) can change in time according to the detection medical target-controlled infusion system of information control (TCI) the infusion efficiency of medicine.
12. detection control apparatus according to claim 1 and 2, is characterized in that: in medical target-controlled infusion system, medical infusion pump comprises 5-10 the array medical injection pump using in parallel;
Described medical infusion pump comprises controller, executor, pump core and the storage medicinal liquid device being connected with pump core input channel, and the opposite side being connected with pump core input channel is sampling probe.
13. array medical injection pump installations according to claim 12, is characterized in that: different array medical injection pumping systems can be respectively to one or two or more kinds while in muscle relaxant, tranquilizer, analgesic, local anesthetic and other classification medicines or according to the successively administration of administration mechanism.
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