Anticancer drug docetaxel Composition analyzed device and detection method
Technical field
The dosage of anticancer drug must be accurate, and when dose deficiency, therapeutic effect can be not achieved.When dose is beyond safety
Dosage can then cause the gastrointestinal reactions such as anorexia, nausea,vomiting,diarrhea.Common and serious toxic reaction is kidney poison
Property reaction, repeated drug taking can aggravate reaction of renal toxicity, and major determinant kidney proximal tubule makes Vacuole formation, exuviation, tube chamber
, there is hyalina, uric acid is excessive in blood, and the symptoms such as blood urine can be caused when serious in expansion.
When large dosage and repeatedly medication, it may appear that neurotoxicity can damage the hair cell that ear Ke replaces mouthpart, cause height
Frequency, which loses, to be listened.
The drug effect of anti-cancer drugs does not have clinical data that can refer to, and initial stage gropes to judge in use, fully relying on doctor,
If during dose deficiency, therapeutic effect is not achieved;If dose can lead to serious toxic reaction beyond safe dose, it can give and suffer from
Person's body brings very major injury.
Invention content
The goal of the invention of the present invention is to overcome the shortcomings of that the drug effect of anti-cancer drugs of the prior art is unknown, provide
A kind of anticancer drug docetaxel Composition analyzed device and detection method that can accurately detect drug effect.
To achieve these goals, the present invention uses following technical scheme:
A kind of anticancer drug docetaxel Composition analyzed device, including operating platform, the electrification on operating platform
Learn work station, flow cell, the first solution bottle for filling cleaning solution and the second solution bottle for filling Docetaxel solution, circulation
Pond is equipped with supporting rack, and supporting rack is equipped with temperature-constant bucket, and water and electric heater are equipped in temperature-constant bucket, substrate, base are equipped in flow cell
Plate is equipped with electrode chip;The cover board of first solution bottle is equipped with inlet tube and outlet tube, and the cover board of the second solution bottle is equipped with
Outlet tube, inlet tube are equipped with solenoid valve, and the outlet tube of the second solution bottle is equipped with the first micro pump, and the first solution bottle goes out liquid
Pipe is equipped with the second micro pump, and in the shape of a spiral, 2 outlet tubes are wound in constant temperature to the outlet tube of the first micro pump and the second micro pump
On bucket, 2 outlet tube lower ends are connect with drain head, and drain head includes several outlet tubes being oliquely downward radially distributed;
Electrode chip with electrochemical workstation including connecting to electrode, reference electrode and working electrode, if there is culture on working electrode
Dry cancer cell, each outlet tube stretch into the working electrode outer edge of flow cell, and flow cell lower part is equipped with outlet tube;Electrification
Work station, the first micro pump, the second micro pump, electric heater and solenoid valve are learned with calculating mechatronics.
When Docetaxel solution is dripped on cancer cell, cancer cell can react, what electrochemical workstation detected
Respective change can occur for current density signal, and detection signal Spect (t) inputs of detected new drug are pre-stored in meter by the present invention
In two layers of stochastic resonance system in calculation machine, computer draws the signal-to-noise ratio spectrogram of excitation noise signal, in signal-to-noise ratio spectrogram
The signal-to-noise ratio peak of the characteristic peak close to origin is chosen, and by the coordinate (M of signal-to-noise ratio peak1, M2) store into computer, meter
Characteristic peaks coordinate (the W of cis-platinum is stored in calculation machine1, W2);
WhenAnd | M2| > | W2|, Computer display Docetaxel compares cis-platinum to the function and effect of cancer cell
Good, the dosage of Docetaxel needs to reduce than cis-platinum;
Work as M1> W1AndWhen, Computer display Docetaxel compares cis-platinum to the function and effect of cancer cell
Difference, the dosage of Docetaxel need to improve than cis-platinum.
The present invention is by the letter of the signal-to-noise ratio peak of the Docetaxel of unknown drug effect and common cancer treatment drugs cis-platinum
It makes an uproar and compares than peak value, under the reference of the cis-platinum of clear and definite drug effect and dose, obtain the drug effect and dose of Docetaxel, be
Docetaxel safe handling provides reliable basis, it is ensured that the safety of patient.
Preferably, support frame as described above includes the annulus for being used to support temperature-constant bucket and several L-shaped branch on annulus
Strut, supporting rod lower end are connect with flow cell;
Tubular insulation cover is equipped with outside the temperature-constant bucket, temperature-constant bucket peripheral surface is equipped with spiral groove, 2 outlet tubes
It is respectively positioned in groove.
Preferably, the second solution bottle is equipped with blender, blender is with calculating mechatronics;Temperature-constant bucket is equipped with temperature
Sensor, temperature sensor is with calculating mechatronics;Liquid level sensor, liquid level sensor and computer are equipped in first solution bottle
Electrical connection.
Preferably, flow cell includes housing, the cover board on housing and the sealing on cover board of upper end opening
Circle, sealing ring lower surface connect the base plate seals of electrode with close, and working electrode and the substrate between electrode are equipped with and lead to
Hole.
A kind of detection method of anticancer drug docetaxel Composition analyzed device, includes the following steps:
(5-1) computer controls electric heater electrified regulation, and the first micro pump drips cleaning solution, and cleaning solution flows through drain
It is heated during pipe, for the first micro pump dropping liquid after 14 to 26 minutes, computer controls the first micro pump to stop dropping liquid;Computer controls
The solenoid valve open time T of the inlet tube of first solution bottle is the first solution bottle additional clean solution;
(5-2) computer controls the second micro pump to drip Docetaxel solution, the second micro pump dropping liquid 23 to 30 minutes
Afterwards, the current density signal S (t) of computer acquisition electrochemical workstation detection, computer select in current density signal S (t)
The sampled value that several time intervals are Δ t is taken, each sampled value is ranked sequentially composition detection signal ES according to time order and function
(t);
(5-3) for first and second sampled value in ES (t) and last, each sampled value ES except two sampled values
(t1), utilize formula
Calculate steady coefficient ratio;
The weight threshold being sequentially increased 0.5,1 and 1.5 is previously provided in computer;
Sampled value in the range of [1-A1,1+A1] is located at for ratio, sampled value is modified to B1ES (t1), B1 is small
In 0.4 real number;
Sampled value in the range of (1-A2,1-A1) or (1+A1,1+A2) is located 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 located at for ratio, sampled value is modified to B3ES
(t1),
(5-4) replaces the correspondence sampled value in ES (t) with corrected each sampled value, obtains believing by modified detection
Number Spect (t),
In two layers of stochastic resonance system that Spect (t) inputs are pre-stored in computer, computer draws excitation noise letter
Number signal-to-noise ratio spectrogram, the signal-to-noise ratio peak of the characteristic peak close to origin is chosen in signal-to-noise ratio spectrogram, and by signal-to-noise ratio peak
Coordinate (M1, M2) store into computer, the characteristic peaks coordinate (W of cis-platinum is stored in computer1, W2);
(5-5) whenAnd | M2| > | W2|, Computer display Docetaxel is to the function and effect ratio of cancer cell
Cis-platinum is good, and the dosage of Docetaxel needs to reduce than cis-platinum;
Work as M1> W1AndWhen, Computer display Docetaxel compares cis-platinum to the function and effect of cancer cell
Difference, the dosage of Docetaxel need to improve than cis-platinum.
Preferably, in two layers of stochastic resonance system that Spect (t) inputs are pre-stored in computer, computer
The signal-to-noise ratio spectrogram for drawing excitation noise signal includes the following steps:
Spect (t) is inputted one layer of 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 setting
Constant, ξ (t) are outer noises, and D is outer noise intensity, and N (t) grasps noise to be interior,For periodic sinusoidal signal,
A is signal amplitude, and f is signal frequency, and t is run duration,For phase, if
cx2-dx4To demarcate component;
Computer calculate V (x, t) for x first derivative and second dervative, and make equation be equal to 0, obtain two layers with
Machine resonance model:
Noise intensity D=0 is set,Spect (t)=0, N (t)=0;The critical value of A is calculated
For
The critical value of A is substituted into one layer of accidental resonance model, and sets X0(t)=0, sn0=0, with quadravalence jade for asking rain Ge Kuta
Algorithm solves one layer of accidental resonance model, obtains
And it calculates
Wherein, xn(t) the n order derivatives for being x (t), sn-1It is value of the n-1 order derivatives of S (t) at t=0, sn+1It is S (t)
Value of the n+1 order derivatives at t=0, n=0,1 ..., N-1;Obtain x1(t), x2(t) ..., xn+1(t) value;
Computer is to x1(t), x2(t) ..., xn+1(t) it is integrated, obtains x (t), and it is random common at one layer to obtain x (t)
Two layers of stochastic resonance system that model and two layers of accidental resonance model form of shaking generate the position x at accidental resonance momentmValue and xm
Corresponding resonance moment t1And and t1Corresponding noise D1, D1For a value in D;
Computer utilizes formulaCalculate the letter of two layers of stochastic resonance system output
It makes an uproar ratio;Wherein, Δ U=a2/4b;Computer draws the signal-to-noise ratio spectrogram of excitation noise signal.
Preferably, the second solution bottle is equipped with blender, blender is with calculating mechatronics;Step (5-1) and (5-2)
Between further include following steps:
Computer controls the blender on the second solution bottle to stop stirring after working 10 to 18 minutes.
Preferably, temperature-constant bucket is equipped with temperature sensor, temperature sensor is with calculating mechatronics;It is characterized in that also
Include the following steps:
Temperature sensor detects the temperature of temperature-constant bucket, and normal temperature section [T is equipped in computerL, TH], when the temperature of detection
Degree >=TH, computer control electric heater stopping heating;As temperature≤T of detectionL, computer control electric heater begin to warm up.
Preferably, being equipped with liquid level sensor in the first solution bottle, liquid level sensor is with calculating mechatronics;Level sensing
Device detects the liquid level in the first solution bottle, and standard value P is equipped in computer:
The step computer controls the solenoid valve open time T of the inlet tube of the first solution bottle, is mended for the first solution bottle
Cleaning solution is filled to be replaced by following step:
When the first solution bottle liquid level sensor detect level value be less than P when, computer control the first solution bottle into
It is closed after the solenoid valve open time T of liquid pipe.
Preferably, further include following steps after step (5-5):
WhenWhen, Computer display it is recommended to increase or reduction dose be 2% to 14%:
WhenWhen, Computer display it is recommended to increase or reduction dose be 14% to 28%;
WhenWhen, Computer display it is recommended to increase or reduction dose be more than 28%.
Therefore, the present invention has the advantages that:Detection efficiency is high, accuracy is good, is used safely for Docetaxel
Provide reliable basis, it is ensured that the safety of patient.
Description of the drawings
Fig. 1 is a kind of structure diagram of the present invention;
Fig. 2 is a kind of functional block diagram of the present invention;
Fig. 3 is a kind of structure diagram of the electrode chip of the present invention;
Fig. 4 is a kind of flow chart of the embodiment of the present invention;
Fig. 5 is a kind of signal-to-noise ratio spectrogram of the cis-platinum 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, the first solution bottle 4, the second solution bottle 5, supporting rack 6,
Temperature-constant bucket 7, electric heater 8, substrate 9, electrode chip 10, the first micro pump 11, the second micro pump 12, drain head 13, computer 14,
Blender 15, temperature sensor 16, liquid level sensor 17, solenoid valve 18, outlet tube 31, annulus 61, L-shaped supporting rod 62, tubular
Insulation cover 71, through-hole 91, painting layer 92, to electrode 1011, reference electrode 1012, working electrode 1013.
Specific embodiment
The present invention will be further described with reference to the accompanying drawings and detailed description.
Embodiment as shown in Figure 1 and Figure 2 is to include operating platform 1, electrochemical workstation 2, stream on operating platform
Logical pond 3 fills the first solution bottle 4 of cleaning solution and fills the second solution bottle 5 of Docetaxel solution, and flow cell is equipped with
Supporting rack 6, supporting rack are equipped with temperature-constant bucket 7, and water and electric heater 8 are equipped in temperature-constant bucket, are equipped with substrate 9 in flow cell, on substrate
Equipped with electrode chip 10;The cover board of first solution bottle is equipped with inlet tube and outlet tube, and the cover board of the second solution bottle is equipped with out
Liquid pipe, inlet tube are equipped with solenoid valve 18, and the outlet tube of the second solution bottle is equipped with the first micro pump 11, and the first solution bottle goes out
Liquid pipe is equipped with the second micro pump 12, and in the shape of a spiral, 2 outlet tubes are wound in the outlet tube of the first micro pump and the second micro pump
On temperature-constant bucket, 2 outlet tube lower ends are connect with drain head 13, and drain head includes oliquely downward radially be distributed 5 and goes out liquid
Pipe;
Each outlet tube stretches into the working electrode outer edge of flow cell, and flow cell lower part is equipped with outlet tube 31;Such as Fig. 2
Shown, electrochemical workstation, the first micro pump, the second micro pump, electric heater and solenoid valve are electrically connected with computer 14.
As shown in figure 3, electrode chip with electrochemical workstation including connecting to electrode 1011, reference electrode 1012 and work
Make electrode 1013, being cultivated on working electrode there are 40000 cancer cells.
As shown in Figure 1, supporting rack includes the annulus 61 for being used to support temperature-constant bucket and several L-shaped support on annulus
Bar 62, supporting rod lower end are connect with flow cell;
Tubular insulation cover 71 is equipped with outside temperature-constant bucket, temperature-constant bucket peripheral surface is equipped with spiral groove, and 2 outlet tubes are equal
In the grooves.
As shown in Fig. 2, the second solution bottle is equipped with blender 15, blender is with calculating mechatronics;Temperature-constant bucket is equipped with
Temperature sensor 16, temperature sensor is with calculating mechatronics;Liquid level sensor 17, liquid level sensor are equipped in first solution bottle
With calculating mechatronics.
Flow cell includes housing, the cover board on housing and the sealing ring on cover board of upper end opening, sealing ring
Lower surface connect the base plate seals of electrode with close, as shown in figure 3, working electrode and the substrate between electrode are equipped with such as
Through-hole 91 shown in Fig. 3, further includes painting layer 92.
As shown in figure 4, a kind of detection method of anticancer drug docetaxel Composition analyzed device, includes the following steps:
Step 100, it preheats, clean
Computer controls electric heater electrified regulation, and temperature sensor detects the temperature of temperature-constant bucket, standard is equipped in computer
Temperature range [TL, TH], as temperature >=T of detectionH, computer control electric heater stopping heating;As temperature≤T of detectionL, meter
Calculation machine control electric heater is begun to warm up;TL=36.5 DEG C, TH=39.6 DEG C.
First micro pump drips cleaning solution, is heated when cleaning solution flows through catheter, the first micro pump dropping liquid 26 divides
Zhong Hou, computer control the first micro pump to stop dropping liquid;When the level value that the liquid level sensor of the first solution bottle detects is less than P
When, computer is closed after controlling the solenoid valve open time T of the inlet tube of the first solution bottle;Cleaning solution is phosphate-buffered
Liquid.
Step 200, it detects
Computer controls the blender on the second solution bottle to stop stirring after working 18 minutes;Computer control second is micro
Pump drips Docetaxel solution, after the second micro pump dropping liquid 30 minutes, the electric current of computer acquisition electrochemical workstation detection
Density signal S (t), computer chooses the sampled value that 500 time intervals are Δ t in current density signal S (t), each to adopt
Sample value is ranked sequentially composition detection signal ES (t) according to time order and function;
Step 300, data correction
For first and second sampled value in ES (t) and last, each sampled value ES (t except two sampled values1),
Utilize formulaCalculate steady coefficient ratio;
The weight threshold being sequentially increased 0.5,1 and 1.5 is previously provided in computer;
Sampled value in the range of [1-A1,1+A1] is located at for ratio, sampled value is modified to B1ES (t1), A1 is
0.16, B1 0.2;
Sampled value in the range of (1-A2,1-A1) or (1+A1,1+A2) is located at for ratio, sampled value is modified to
B2ES(t1), B1 0.4;
Sampled value in the range of [0.5,1-A2] or [1+A2,1.5] is located at for ratio, sampled value is modified to B3ES
(t1), B3 0.7;
Step 400, the signal-to-noise ratio peak at selected characteristic peak
The correspondence sampled value in ES (t) is replaced with corrected each sampled value, is obtained by modified detection signal
Spect (t),
In two layers of stochastic resonance system that Spect (t) inputs are pre-stored in computer, computer draws excitation and makes an uproar
The signal-to-noise ratio spectrogram of acoustical signal includes the following steps:
Spect (t) is inputted one layer of 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 setting
Constant, ξ (t) are outer noises, and D is outer noise intensity, and N (t) grasps noise to be interior,For periodic sinusoidal signal, A
It is signal amplitude, f is signal frequency, and t is run duration,For phase, if
cx2-dx4To demarcate component;
Computer calculate V (x, t) for x first derivative and second dervative, and make equation be equal to 0, obtain two layers with
Machine resonance model:
Noise intensity D=0 is set,Spect (t)=0, N (t)=0;The critical value of A is calculated
For
The critical value of A is substituted into one layer of accidental resonance model, and sets X0(t)=0, sn0=0, with quadravalence jade for asking rain Ge Kuta
Algorithm solves one layer of accidental resonance model, obtains
And it calculates
Wherein, xn(t) the n order derivatives for being x (t), snn-1It is value of the n-1 order derivatives of S (t) at t=0, snn+1It is S
(t) value of the n+1 order derivatives at t=0, n=0,1 ..., N-1;Obtain x1(t), x2(t) ..., xn+1(t) value;
Computer is to x1(t), x2(t) ..., xn+1(t) it is integrated, obtains x (t), and it is random common at one layer to obtain x (t)
Two layers of stochastic resonance system that model and two layers of accidental resonance model form of shaking generate the position x at accidental resonance momentmValue and xm
Corresponding resonance moment t1And and t1Corresponding noise D1, D1For a value in D;
Computer utilizes formulaCalculate the letter of two layers of stochastic resonance system output
It makes an uproar ratio;Wherein, Δ U=a2/4b;Computer draws the signal-to-noise ratio spectrogram of excitation noise signal;
The signal-to-noise ratio peak of the characteristic peak close to origin is chosen in signal-to-noise ratio spectrogram, and by the coordinate of signal-to-noise ratio peak
(M1, M2) store into computer, the characteristic peaks coordinate (W of cis-platinum is stored in computer1, W2);The characteristic peaks of cis-platinum are sat
Mark (W1, W2) equally it is to be obtained using the method for step 100 to 400, the cisplatin solution being contained in respectively in 2 the second solution bottles
It is identical with Docetaxel concentration.
Step 500, function and effect are made and dose judges
WhenAnd | M2| > | W2|, Computer display Docetaxel compares cis-platinum to the function and effect of cancer cell
Good, the dosage of Docetaxel needs to reduce than cis-platinum;
Work as M1> W1AndWhen, Computer display Docetaxel compares cis-platinum to the function and effect of cancer cell
Difference, the dosage of Docetaxel need to improve than cis-platinum;
WhenWhen, Computer display it is recommended to increase or reduction dose be 2% to 14%;
WhenWhen, Computer display it is recommended to increase or reduction dose be 14% to 28%;
WhenWhen, Computer display it is recommended to increase or reduction dose be more than 28%.
As shown in Figure 5, Figure 6, the signal-to-noise ratio peak of the characteristic peak of cis-platinum be (20, -34dB), the characteristic peak of Docetaxel
Signal-to-noise ratio peak be (5, -44dB);
Therefore, Computer display Docetaxel is better than cis-platinum to the function and effect of cancer cell, the medication of Docetaxel
Amount needs the information reduced than cis-platinum.
The dose that Computer display suggestion reduces is 35%.
It should be understood that this embodiment is only used to illustrate the invention but not to limit the scope of the invention.In addition, it should also be understood that,
After having read the content of the invention lectured, those skilled in the art can make various modifications or changes to the present invention, these etc.
Valency form is also fallen within the scope of the appended claims of the present application.