Anticancer drug docetaxel Composition analyzed device and detection method
Technical field
The dosage of cancer therapy drug accurately when dose deficiency, must can not reach therapeutic effect.When dose is beyond safe dose, then can cause the gastrointestinal reaction such as loss of appetite, nausea,vomiting,diarrhea.The most serious common toxic reaction is Toxicity of Kidney reaction, and repeated drug taking can aggravate nephrotoxicity reaction, major determinant kidney proximal tubule, make Vacuole formation, exuviation, lumen distention, hyaline cast occur, in blood, uric acid is too much, can cause the symptoms such as hematuria time serious.
When heavy dose and repeatedly medication, it may appear that neurotoxicity, ear Ke hair cell for mouthpart can be damaged, cause high frequency to lose and listen.
The drug effect of PTS does not has clinical data to be referred to, and when the initial stage uses, fully rely on doctor gropes judgement, if during dose deficiency, not reaching therapeutic effect;If dose can cause serious toxic reaction beyond safe dose, very major injury can be brought to patient body.
Summary of the invention
The goal of the invention of the present invention is to overcome the deficiency that the drug effect of PTS of the prior art is not clear, it is provided that a kind of anticancer drug docetaxel Composition analyzed device that can accurately detect drug effect and detection method.
To achieve these goals, the present invention is by the following technical solutions:
A kind of anticancer drug docetaxel Composition analyzed device, including operating platform, electrochemical workstation, the flow cell be located on operating platform, fill the first solution bottle of cleaning solution and fill the second solution bottle of Docetaxel solution, flow cell is provided with bracing frame, bracing frame is provided with temperature-constant bucket, being provided with water and electric heater in temperature-constant bucket, be provided with substrate in flow cell, substrate is provided with electrode chip;The cover plate of the first solution bottle is provided with feed tube and drain pipe, the cover plate of the second solution bottle is provided with drain pipe, electromagnetic valve it is equipped with on feed tube, the drain pipe of the second solution bottle is provided with the first micro pump, the drain pipe of the first solution bottle is provided with the second micro pump, and in the shape of a spiral, 2 drain pipes are wound on temperature-constant bucket the drain pipe of the first micro pump and the second micro pump, article 2, drain pipe lower end is connected with drain head, and drain head includes several drain pipes being distributed the most radially;Electrode chip include being connected with electrochemical workstation to electrode, reference electrode and working electrode, working electrode is cultivated and has several cancerous cell, each drain pipe all stretches into the working electrode outer edge of flow cell, and flow cell bottom is provided with drain pipe;Electrochemical workstation, the first micro pump, the second micro pump, electric heater and electromagnetic valve all electrically connect with computer.
When Docetaxel solution drips on cancerous cell, cancerous cell can react, the current density signal that electrochemical workstation detects can occur respective change, detection signal Spect (t) of detected new drug is inputted in the second order stochastic resonance system being pre-stored in computer by the present invention, computer draws the signal to noise ratio spectrogram of excitation noise signal, the signal-to-noise ratio peak of the characteristic peak near initial point is chosen in signal to noise ratio spectrogram, and by the coordinate (M of signal-to-noise ratio peak1, M2) store in computer, in computer, storage has the characteristic peaks coordinate (W of cisplatin1, W2);
WhenAnd | M2| > | W2|, Computer display Docetaxel is better than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to reduce than cisplatin;
Work as M1> W1AndTime, Computer display Docetaxel is poorer than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to improve than cisplatin.
The present invention by the signal-to-noise ratio peak of the Docetaxel of unknown drug effect compared with the signal-to-noise ratio peak of the cancer treatment drugs cisplatin commonly used, under the reference of the cisplatin of the clearest and the most definite drug effect and dose, obtain drug effect and the dose of Docetaxel, reliable basis is provided, it is ensured that the safety of patient for Docetaxel safe handling.
As preferably, support frame as described above includes the annulus for supporting temperature-constant bucket and some the L-shaped support bars being located on annulus, and support bar lower end is connected with flow cell;
Being provided with tubular thermal insulation cover outside described temperature-constant bucket, temperature-constant bucket outer peripheral face is provided with spiral groove, and 2 drain pipes are respectively positioned in groove.
As preferably, the second solution bottle is provided with agitator, and agitator electrically connects with computer;Temperature-constant bucket is provided with temperature sensor, and temperature sensor electrically connects with computer;Being provided with liquid level sensor in first solution bottle, liquid level sensor electrically connects with computer.
As preferably, flow cell includes the housing of upper end open, the cover plate being located on housing and the sealing ring being located on cover plate, and sealing ring lower surface is connected with near to the base plate seals of electrode, working electrode and the substrate between electrode is provided with through hole.
The detection method of a kind of anticancer drug docetaxel Composition analyzed device, comprises the steps:
(5-1) computer controls electric heater electrified regulation, and the first micro pump drips cleaning solution, and cleaning solution flows through during catheter heated, and the first micro pump dropping liquid is after 14 to 26 minutes, and computer controls the first micro pump and stops dropping liquid;Computer controls the solenoid valve open time T of the feed tube of the first solution bottle, is the first solution bottle additional clean solution;
(5-2) computer controls the second micro pump and drips Docetaxel solution, second micro pump dropping liquid is after 23 to 30 minutes, current density signal S (t) of computer acquisition electrochemical workstation detection, the sampled value that several time intervals are Δ t chosen in current density signal S (t) by computer, and each sampled value is arranged to make up detecting signal ES (t) according to time order and function order;
(5-3) in ES (t) first and second sampled value and last, each sampled value ES (t outside two sampled values1), utilize formula
Calculate steady coefficient ratio;
Computer is previously provided with the weight threshold 0.5,1 and 1.5 increased successively;
Sampled value in the range of [1-A1,1+A1] is positioned at for ratio, sampled value is modified to B1ES (t1), B1 is the real number less than 0.4;
Sampled value in the range of (1-A2,1-A1) or (1+A1,1+A2) is positioned at for ratio, sampled value is modified to B2ES (t1),
Sampled value in the range of [0.5,1-A2] or [1+A2,1.5] is positioned at for ratio, sampled value is modified to B3ES (t1),
(5-4) replace the corresponding sampled value in ES (t) by each sampled value corrected, obtain detection signal Spect (t) through revising,
In the second order stochastic resonance system that Spect (t) input is pre-stored in computer, computer draws the signal to noise ratio spectrogram of excitation noise signal, the signal-to-noise ratio peak of the characteristic peak near initial point is chosen in signal to noise ratio spectrogram, and by the coordinate (M of signal-to-noise ratio peak1, M2) store in computer, in computer, storage has the characteristic peaks coordinate (W of cisplatin1, W2);
(5-5) whenAnd | M2| > | W2|, Computer display Docetaxel is better than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to reduce than cisplatin;
Work as M1> W1AndTime, Computer display Docetaxel is poorer than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to improve than cisplatin.
As preferably, in described second order stochastic resonance system Spect (t) input being pre-stored in computer, computer draws the signal to noise ratio spectrogram of excitation noise signal and comprises the steps:
Spect (t) is inputted single order accidental resonance model by computer
In, wherein, V (x, t) is potential function, and x (t) is Brownian movement Particles Moving lopcus function, and a, b, c, d are the constant set, and ξ (t) is outer noise, and D is outer noise intensity, and N (t) grasps noise in being,For periodic sinusoidal signal, A is signal amplitude, and f is signal frequency, and t is movement time,For phase place, ifcx2-dx4For demarcating component;
Computer calculate V (x, t) for first derivative and the second dervative of x, and makes equation be equal to 0, obtains two layers of accidental resonance model:
Set noise intensity D=0,Spect (t)=0, N (t)=0;The marginal value being calculated A is
The marginal value of A is substituted in one layer of accidental resonance model, and sets X0(t)=0, sn0=0, with quadravalence one layer of accidental resonance model of jade for asking rain Ge Kuta Algorithm for Solving, obtain And calculate
Wherein, xnT () is the n order derivative of x (t), snn-1It is the n-1 order derivative of S (t) value at t=0, snn+1It is the n+1 order derivative of S (t) value at t=0, n=0,1 ..., N-1;Obtain x1(t), x2(t) ..., xn+1The value of (t);
Computer is to x1(t), x2(t) ..., xn+1T () is integrated, obtain x (t), and obtain the x (t) the position x in the second order stochastic resonance system generation accidental resonance moment of one layer of accidental resonance model and two layers of accidental resonance model compositionmValue and xmCorresponding resonance moment t1And and t1Corresponding noise D1, D1For a value in D;
Computer utilizes formulaCalculate the signal to noise ratio that second order accidental resonance system, computer draws the letter system output of excitation noise signal;Wherein, Δ U=a2/4b;Make an uproar and compare spectrogram.
As preferably, the second solution bottle is provided with agitator, and agitator electrically connects with computer;Also comprise the steps: between step (5-1) and (5-2)
Computer controls to stop stirring after the agitator on the second solution bottle works 10 to 18 minutes.
As preferably, temperature-constant bucket is provided with temperature sensor, and temperature sensor electrically connects with computer;It is characterized in that, also comprise the steps:
The temperature of temperature sensor detection temperature-constant bucket, is provided with the interval [T of standard temperature in computerL, TH], as the temperature >=T of detectionH, computer controls electric heater and stops heating;Temperature≤T when detectionL, computer controls electric heater and begins to warm up.
As preferably, being provided with liquid level sensor in the first solution bottle, liquid level sensor electrically connects with computer;Liquid level sensor detects the liquid level in the first solution bottle respectively, is provided with standard value P in computer;
Described step computer controls the solenoid valve open time T of the feed tube of the first solution bottle, is that the first solution bottle additional clean solution is replaced by following step:
When the level value that the liquid level sensor of the first solution bottle detects is less than P, computer cuts out after controlling the solenoid valve open time T of the feed tube of the first solution bottle.
As preferably, also comprise the steps: after step (5-5)
WhenTime, the dose that Computer display suggestion is increased or decreased is 2% to 14%;
WhenTime, the dose that Computer display suggestion is increased or decreased is 14% to 28%;
WhenTime, the dose that Computer display suggestion is increased or decreased is more than 28%.
Therefore, there is advantages that detection efficiency is high, accuracy is good, provide reliable basis for Docetaxel safe handling, it is ensured that the safety of patient.
Accompanying drawing explanation
Fig. 1 is a kind of structural representation of the present invention;
Fig. 2 is a kind of theory diagram of the present invention;
Fig. 3 is a kind of structural representation of the electrode chip of the present invention;
Fig. 4 is a kind of flow chart of embodiments of the invention;
Fig. 5 is a kind of signal to noise ratio spectrogram of the cisplatin of the present invention;
Fig. 6 is a kind of signal to noise ratio spectrogram of the Docetaxel of the present invention.
In figure: operating platform 1, electrochemical workstation 2, flow cell 3, first solution bottle 4, second solution bottle 5, bracing frame 6, temperature-constant bucket 7, electric heater 8, substrate 9, electrode chip 10, first micro pump 11, second micro pump 12, drain head 13, computer 14, agitator 15, temperature sensor 16, liquid level sensor 17, electromagnetic valve 18, drain pipe 31, annulus 61, L-shaped support bar 62, tubular thermal insulation cover 71, through hole 91, painting layer 92, to electrode 1011, reference electrode 1012, working electrode 1013.
Detailed description of the invention
The present invention will be further described with detailed description of the invention below in conjunction with the accompanying drawings.
Embodiment as shown in Figure 1 and Figure 2 is to include operating platform 1, electrochemical workstation 2, the flow cell 3 be located on operating platform, fill the first solution bottle 4 of cleaning solution and fill the second solution bottle 5 of Docetaxel solution, flow cell is provided with bracing frame 6, bracing frame is provided with temperature-constant bucket 7, temperature-constant bucket is provided with water and electric heater 8, being provided with substrate 9 in flow cell, substrate is provided with electrode chip 10;The cover plate of the first solution bottle is provided with feed tube and drain pipe, the cover plate of the second solution bottle is provided with drain pipe, electromagnetic valve 18 it is equipped with on feed tube, the drain pipe of the second solution bottle is provided with the first micro pump 11, the drain pipe of the first solution bottle is provided with the second micro pump 12, and in the shape of a spiral, 2 drain pipes are wound on temperature-constant bucket the drain pipe of the first micro pump and the second micro pump, article 2, drain pipe lower end is connected with drain head 13, and drain head includes 5 drain pipes being distributed the most radially;
Each drain pipe all stretches into the working electrode outer edge of flow cell, and flow cell bottom is provided with drain pipe 31;As in figure 2 it is shown, electrochemical workstation, the first micro pump, the second micro pump, electric heater and electromagnetic valve all electrically connect with computer 14.
As it is shown on figure 3, electrode chip include being connected with electrochemical workstation to electrode 1011, reference electrode 1012 and working electrode 1013, working electrode is cultivated and has 40000 cancerous cell.
As it is shown in figure 1, bracing frame includes the annulus 61 for supporting temperature-constant bucket and some the L-shaped support bars 62 being located on annulus, support bar lower end is connected with flow cell;
Being provided with tubular thermal insulation cover 71 outside temperature-constant bucket, temperature-constant bucket outer peripheral face is provided with spiral groove, and 2 drain pipes are respectively positioned in groove.
As in figure 2 it is shown, the second solution bottle is provided with agitator 15, agitator electrically connects with computer;Temperature-constant bucket is provided with temperature sensor 16, and temperature sensor electrically connects with computer;Being provided with liquid level sensor 17 in first solution bottle, liquid level sensor electrically connects with computer.
Flow cell includes the housing of upper end open, the cover plate being located on housing and the sealing ring being located on cover plate, sealing ring lower surface is connected with the close base plate seals to electrode, as it is shown on figure 3, working electrode and the substrate between electrode is provided with through hole 91 as shown in Figure 3, also include painting layer 92.
As shown in Figure 4, the detection method of a kind of anticancer drug docetaxel Composition analyzed device, comprise the steps:
Step 100, preheats, cleans
Computer controls electric heater electrified regulation, the temperature of temperature sensor detection temperature-constant bucket, is provided with the interval [T of standard temperature in computerL, TH], as the temperature >=T of detectionH, computer controls electric heater and stops heating;Temperature≤T when detectionL, computer controls electric heater and begins to warm up;TL=36.5 DEG C, TH=39.6 DEG C.
First micro pump drips cleaning solution, and cleaning solution flows through during catheter heated, and after the first micro pump dropping liquid 26 minutes, computer controls the first micro pump and stops dropping liquid;When the level value that the liquid level sensor of the first solution bottle detects is less than P, computer cuts out after controlling the solenoid valve open time T of the feed tube of the first solution bottle;Cleaning solution is phosphate buffer.
Step 200, detection
Computer controls to stop stirring after the agitator on the second solution bottle works 18 minutes;Computer controls the second micro pump and drips Docetaxel solution, after second micro pump dropping liquid 30 minutes, current density signal S (t) of computer acquisition electrochemical workstation detection, the sampled value that 500 time intervals are Δ t chosen in current density signal S (t) by computer, and each sampled value is arranged to make up detecting signal ES (t) according to time order and function order;
Step 300, data correction
For in ES (t) first and second sampled value and last, each sampled value ES (t outside two sampled values1), utilize formula Calculate steady coefficient ratio;
Computer is previously provided with the weight threshold 0.5,1 and 1.5 increased successively;
Sampled value in the range of [1-A1,1+A1] is positioned at for ratio, sampled value is modified to B1ES (t1), A1 is 0.16, and B1 is 0.2;
Sampled value in the range of (1-A2,1-A1) or (1+A1,1+S2) is positioned at for ratio, sampled value is modified to B2ES (t1), B1 is 0.4;
Sampled value in the range of [0.5,1-S2] or [1+A2,1.5] is positioned at for ratio, sampled value is modified to B3ES (t1), B3 is 0.7;
Step 400, the signal-to-noise ratio peak at selected characteristic peak
Replace the corresponding sampled value in ES (t) by each sampled value corrected, obtain detection signal Spect (t) through revising,
In described second order stochastic resonance system Spect (t) input being pre-stored in computer, computer draws the signal to noise ratio spectrogram of excitation noise signal and comprises the steps:
Spect (t) is inputted single order accidental resonance model by computer
In, wherein, V (x, t) is potential function, and x (t) is Brownian movement Particles Moving lopcus function, and a, b, c, d are the constant set, and ξ (t) is outer noise, and D is outer noise intensity, and N (t) grasps noise in being,For periodic sinusoidal signal, S is signal amplitude, and f is signal frequency, and t is movement time,For phase place, ifcx2-dx4For demarcating component;
Computer calculate V (x, t) for first derivative and the second dervative of x, and makes equation be equal to 0, obtains two layers of accidental resonance model:
Set noise intensity D=0,Spect (t)=0, N (t)=0;The marginal value being calculated A is
The marginal value of A is substituted in one layer of accidental resonance model, and sets X0(t)=0, sn0=0, with quadravalence one layer of accidental resonance model of jade for asking rain Ge Kuta Algorithm for Solving, obtain And calculate
Wherein, xnT () is the n order derivative of x (t), snn-1It is the n-1 order derivative of S (t) value at t=0, snn+1It is the n+1 order derivative of S (t) value at t=0, n=0,1 ..., N-1;Obtain x1(t), x2(t) ..., xn+1The value of (t);
Computer is to x1(t), x2(t) ..., xn+1T () is integrated, obtain x (t), and obtain the x (t) the position x in the second order stochastic resonance system generation accidental resonance moment of one layer of accidental resonance model and two layers of accidental resonance model compositionmValue and xmCorresponding resonance moment t1And and t1Corresponding noise D1, D1For a value in D;
Computer utilizes formulaCalculate the signal to noise ratio that second order accidental resonance system, computer draws the letter system output of excitation noise signal;Wherein, Δ U=a2/4b;Make an uproar and compare spectrogram;
The signal-to-noise ratio peak of the characteristic peak near initial point is chosen in signal to noise ratio spectrogram, and by the coordinate (M of signal-to-noise ratio peak1, M2) store in computer, in computer, storage has the characteristic peaks coordinate (W of cisplatin1, W2);Characteristic peaks coordinate (the W of cisplatin1, W2) it is that the method using step 100 to 400 obtains equally, the cisplatin solution being contained in respectively in 2 the second solution bottles is identical with Docetaxel concentration
Step 500, makes action effect and dose judges
WhenAnd | M2| > | W2|, Computer display Docetaxel is better than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to reduce than cisplatin;
Work as M1> W1AndTime, Computer display Docetaxel is poorer than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs to improve than cisplatin;
WhenTime, the dose that Computer display suggestion is increased or decreased is 2% to 14%;
WhenTime, the dose that Computer display suggestion is increased or decreased is 14% to 28%;
WhenTime, the dose that Computer display suggestion is increased or decreased is more than 28%.
As shown in Figure 5, Figure 6, the signal-to-noise ratio peak of the characteristic peak of cisplatin is (20 ,-34dB), and the signal-to-noise ratio peak of the characteristic peak of Docetaxel is (5 ,-44dB);
Therefore, Computer display Docetaxel is better than cisplatin to the action effect of cancerous cell, and the dosage of Docetaxel needs the information reduced than cisplatin.
The dose that Computer display suggestion reduces is 35%.
Should be understood that the present embodiment is merely to illustrate the present invention rather than limits the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, the present invention can be made various changes or modifications by those skilled in the art, and these equivalent form of values fall within the application appended claims limited range equally.