CN110376100B - Solid lipid nanoparticle controlled release performance test system - Google Patents
Solid lipid nanoparticle controlled release performance test system Download PDFInfo
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Abstract
The invention provides a system for testing the release control performance of solid lipid nanoparticles, which utilizes an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device and a monitoring platform to carry out real-time and efficient monitoring on the release performance of the solid lipid nanoparticles, wherein during testing, sodium chloride solution is wrapped in a lipoid core to prepare solid colloidal particles at a preset temperature, the solid colloidal particles are placed in phosphate solution, the solid colloidal particles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolving process of the solid colloidal particles, the conductivity sensor is used for detecting a conductivity signal of the phosphate solution during the dissolving process of the solid colloidal particles, the central processing device converts the received conductivity signal into a conductivity value, and draws a conductivity-time spectrum to be transmitted to the display device for displaying, and simultaneously, the conductivity-time spectrum is transmitted to the monitoring platform through a wireless transmission device.
Description
Technical Field
The invention relates to the field of intelligent medicine performance testing, in particular to a system for testing the controlled release performance of solid lipid nanoparticles.
Background
Solid Lipid Nanoparticles (SLNs) are a novel drug carrier, and have the advantages of targeted drug delivery, long-term stability, good physiological compatibility and drug sustained release. It can be absorbed by oral administration, skin administration, pulmonary administration, etc.
With the continuous development of medicine, the traditional administration mode cannot meet various medical requirements, such as: prolonging the action time of the medicine in vivo, improving the bioavailability, reducing the toxicity of the medicine, and the like. In the 80 s of the 20 th century, after a series of drug carriers such as liposome, microemulsion, polymer nanoparticles and the like are developed, people gradually turn the attention to solid lipid nanoparticles taking natural lipid materials which are physiologically compatible and degraded in vivo as carriers.
The SLN takes solid lipoid compound (natural or synthetic) as a carrier, and the drug is wrapped in a lipoid core to prepare the solid lipid nanoparticle, so that the SLN has the advantages of the traditional carrier system and simultaneously overcomes the defects. SLN can be treated by various administration modes such as oral administration, injection, epidermal administration, pulmonary administration and the like. Meanwhile, SLN also shows advantages in various aspects such as biotoxicity, degradability, and long-term stability. And because the preparation process contains the basis of large-scale production, SLN is more attractive than polymer nanoparticles.
As a novel drug carrier, the Solid Lipid Nanoparticle (SLN) has good biocompatibility, obvious slow release effect and good targeting property, can achieve the expected targets (skin, injection, oral administration and the like) through various drug delivery modes, simultaneously has the advantages of high physical stability and slow drug leakage of the polymeric nanoparticle, has the advantages of low toxicity and large-scale production of liposome emulsion, and is a novel drug delivery system carrier with great development prospect. At present, SLN research is mainly focused on structural characteristics, preparation methods and the like. SLN has different structural characteristics compared with liposome and microemulsion, and is a nano-drug delivery system prepared by taking natural or artificially synthesized solid lipid (such as saturated fatty glyceride, stearic acid, mixed lipid and the like) as a carrier and adsorbing or wrapping a drug in a lipid core. As a consequence, SLNs also display some characteristics that are different from other liposomes themselves.
In the prior art, patent CN106860425A provides a chloramphenicol solid lipid nanoparticle, which relates to a test of the release performance of the solid lipid nanoparticle, and calculates the release performance of the solid lipid nanoparticle by the concentration of the solid lipid nanoparticle diffused into a hydrochloric acid solution, but the release performance of the drug cannot be monitored in real time, and the test precision is not high, and the release performance of the solid lipid nanoparticle cannot be accurately expressed.
Disclosure of Invention
Therefore, in order to overcome the above problems, the present invention provides a system for testing the release performance of solid lipid nanoparticles, which utilizes an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device and a monitoring platform to perform real-time and efficient monitoring on the release performance of solid lipid nanoparticles, wherein during the testing, at a preset temperature, a sodium chloride solution is wrapped in a lipid core to prepare solid lipid nanoparticles, the solid lipid nanoparticles are placed in a phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the solid lipid nanoparticles release the sodium chloride solution during the dissolution, the image acquisition device is used to acquire image information during the dissolution of the solid lipid nanoparticles, the conductivity sensor is used to detect a conductivity signal of the phosphate solution during the dissolution of the solid lipid nanoparticles, the image acquisition device transmits the acquired image information of the solid lipid nanoparticle dissolving process to the image processing module for image processing, the image processing module transmits the processed image to the central processing device, the conductivity sensor transmits the collected conductivity signal to the signal processing circuit for signal processing, the signal processing circuit transmits the processed signal to the central processing device, the central processing device transmits the received image information to the display device for display, the central processing device transmits the received image information to the monitoring platform through the wireless transmission device, the central processing device converts the received conductivity signal into a conductivity value, and drawing a conductivity-time spectrum, transmitting the conductivity-time spectrum to a display device for displaying, and transmitting the conductivity-time spectrum to a monitoring platform through a wireless transmission device.
The system for testing the controlled release performance of the solid lipid nanoparticles comprises an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device and a monitoring platform.
The output end of the image acquisition device is connected with the input end of the image processing module, the output end of the conductivity sensor is connected with the input end of the signal processing circuit, the output end of the image processing module is connected with the input end of the central processing device, the output end of the signal processing circuit is connected with the input end of the central processing device, the output end of the central processing device is connected with the input end of the display device, and the central processing device is connected with the input end of the monitoring platform through the wireless transmission device.
During testing, at a preset temperature, a sodium chloride solution is wrapped in a lipoid core to prepare solid lipid nanoparticles, the solid lipid nanoparticles are placed in a phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolving process of the solid lipid nanoparticles, an image acquisition device is used for acquiring image information during the dissolving process of the solid lipid nanoparticles, a conductivity sensor is used for detecting conductivity signals of the phosphate solution during the dissolving process of the solid lipid nanoparticles, the image acquisition device transmits the acquired image information during the dissolving process of the solid lipid nanoparticles to an image processing module for image processing, the image processing module transmits the processed images to a central processing device, the conductivity sensor transmits the acquired conductivity signals to a signal processing circuit for signal processing, and the signal processing circuit transmits the processed signals to the central processing device, the central processing device transmits the received conductivity signals and the image information to the display device for displaying, and the central processing device transmits the received conductivity signals and the image information to the monitoring platform through the wireless transmission device.
Preferably, the image acquisition device is used for acquiring image information of the solid lipid nanoparticle dissolution process, the image acquisition device transmits the acquired image information of the solid lipid nanoparticle dissolution process to the image processing module for image processing, and the image processing module comprises an image filtering unit, an image smoothing unit and an image enhancement unit.
The output end of the image acquisition device is connected with the input end of the image filtering unit, the output end of the image filtering unit is connected with the input end of the image smoothing unit, the output end of the image smoothing unit is connected with the input end of the image enhancement unit, and the output end of the image enhancement unit is connected with the input end of the central processing unit.
Preferably, the image transmitted from the image acquisition device to the image processing module is defined as a two-dimensional function f (x, y), where x and y are spatial coordinates, the image filtering unit performs image filtering processing on the two-dimensional function f (x, y), and the two-dimensional function of the image after the image filtering processing is g (x, y), where σ is a filtering parameter, and the filtering effect is adjusted by σ,
g(x，y)＝f(x，y)·G(x，y)。
preferably, the image smoothing unit performs image smoothing on an image two-dimensional function g (x, y), where the image two-dimensional function after the image smoothing is h (x, y), where the smoothing function is q (x, y), and then there is,
h(x，y)＝q(x，y)*g(x，y)；
wherein, the symbol is convolution symbol, gamma is self-defined adjustable constant, and the smooth function is controlled by gamma.
Preferably, the image enhancement unit performs image enhancement processing on the two-dimensional image function h (x, y), and the two-dimensional image function after the image enhancement processing is k (x, y), if,
the image enhancement unit transmits the image two-dimensional function k (x, y) to the central processing device.
Preferably, the conductivity sensor is used for detecting conductivity signals of the phosphate solution in the dissolving process of the solid lipid nanoparticles, the conductivity sensor transmits the collected conductivity signals to the signal processing circuit for signal processing, the signal processing circuit sequentially performs signal amplification and signal filtering on the received conductivity signals, the signal processing circuit transmits the processed signals to the central processing device, the central processing device transmits the received conductivity signals to the display device for display, and the central processing device transmits the received conductivity signals to the monitoring platform through the wireless transmission device.
Preferably, the conductivity sensor is used for collecting conductivity signals of phosphate solution in the dissolving process of the solid lipid nanoparticles, the conductivity sensor converts the collected conductivity signals into current signals I0 and transmits the current signals I0 to the signal processing circuit, V1 is voltage signals processed by the signal processing circuit, the signal processing circuit comprises a signal amplifying unit and a signal filtering unit, the output end of the conductivity sensor is connected with the input end of the signal amplifying unit, the output end of the signal amplifying unit is connected with the input end of the signal filtering unit, and the output end of the signal filtering unit is connected with the input end of the central processing device.
Preferably, the signal amplification unit comprises an integrated operational amplifier A1-A2, a capacitor C1-C4, a triode VT1-VT4 and a resistor R1-R10.
Wherein, the output end of the conductivity sensor is connected with one end of a resistor R1, the other end of a resistor R1 is connected with the inverting input end of an integrated operational amplifier A1, the non-inverting input end of the integrated operational amplifier A1 is grounded, the other end of the resistor R1 is connected with one end of a capacitor C1, one end of the capacitor C2 connected with the resistor R2 in parallel is connected with the other end of a resistor R2, the other end of the capacitor C2 connected with the resistor R2 in parallel is connected with a signal filtering unit, the other end of a capacitor C1 is connected with the output end of the integrated operational amplifier A1, the output end of the integrated operational amplifier A1 is connected with the input end of the integrated operational amplifier A2, one end of a capacitor C3 is grounded, the other end of a capacitor C3 is connected with a +15V power supply, one end of the capacitor C4 is grounded, the other end of a capacitor C4 is connected with a-15V power supply, the other end of a capacitor C4 is also connected with one end of a resistor R4, the other end of the resistor R4 is connected with the V-end of the integrated operational amplifier A2, the other end of the resistor R4 is further connected with a base of a triode VT4, one end of a resistor R3 is connected with a V + end of the integrated operational amplifier A2, one end of a resistor R3 is connected with a base of a triode VT3, one end of a resistor R3 is further connected with a collector of a triode VT1, the other end of a resistor R3 is connected with a +15V power supply, one end of a resistor R10 is connected with a collector of a triode VT2, a collector of the triode VT2 is further connected with a-15V power supply, the other end of a resistor R10 is connected with an emitter of a triode VT4, one end of a resistor R9 is connected with a base of a triode VT2, the other end of a resistor R9 is connected with the other end of a resistor R10, a collector of a triode VT2 is connected with a base of a triode VT4, one end of the resistor R8 is grounded, the other end of the resistor R8 is connected with an output end of the integrated operational amplifier A2, the other end of the resistor R8 is further connected with one end of a resistor R7, and the other end of the resistor R7 is connected with a collector 4, the collector of the triode VT4 is connected with the collector of the triode VT3, the base of the triode VT3 is connected with the collector of the triode VT1, one end of the resistor R6 is connected with the base of the triode VT1, the other end of the resistor R6 is connected with the collector of the triode VT3, one end of the resistor R5 is connected with the collector of the triode VT1, and the other end of the resistor R5 is connected with the other end of the resistor R6.
Preferably, the signal filtering unit comprises resistors R11-R20, capacitors C5-C11 and an integrated operational amplifier A3-A6.
Wherein, the output end of the signal amplifying unit is connected with one end of a resistor R11, the other end of a resistor R11 is connected with one end of a capacitor C5, one end of a resistor R15 is grounded, the other end of a resistor R15 is connected with one end of a resistor R14, the other end of a resistor R15 is connected with the non-inverting input end of an integrated operational amplifier A3, the other end of a resistor R14 is connected with one end of a resistor R13, the other end of a resistor R14 is also connected with the output end of an integrated operational amplifier A4, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A3, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A4, the other end of a resistor R13 is also connected with one end of a capacitor C7, the other end of a capacitor C7 is connected with the output end of an integrated operational amplifier A3, the other end of a capacitor C7 is connected with one end of a resistor R12, the other end of a resistor R12 is connected with one end of a capacitor C6, the non-inverting input end of a resistor R4 is also connected with the input end of an integrated operational amplifier R12, the other end of the capacitor C6 is connected with the other end of the capacitor C5, the other end of the capacitor C5 is further connected with one end of the capacitor C8, one end of the resistor R19 is grounded, the other end of the resistor R19 is connected with one end of the resistor R18, the other end of the resistor R19 is connected with the non-inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R18 is connected with one end of the resistor R17, the other end of the resistor R18 is further connected with the output terminal of the integrated operational amplifier a6, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier a6, the other end of the resistor R17 is further connected with one end of the capacitor C10, the other end of the capacitor C10 is connected with the output terminal of the integrated operational amplifier A5, the other end of the capacitor C10 is connected with one end of the resistor R16, the other end of the resistor R16 is connected with the non-inverting input terminal of the capacitor C9, the integrated operational amplifier R16 is further connected with the non-inverting input terminal 6 of the integrated operational amplifier a6, the other end of the capacitor C9 is connected with the other end of the capacitor C8, the other end of the capacitor C8 is further connected with one end of the capacitor C11, one end of the resistor R20 is grounded, the other end of the resistor R20 is connected with the other end of the capacitor C11, the other end of the resistor R20 is connected with the input end of the central processing unit, and the signal filtering unit transmits the voltage signal V1 to the ADC port of the central processing unit.
Preferably, the central processing device converts the received conductivity signal into a conductivity value, and draws a conductivity-time spectrum to be transmitted to the display device for display, and simultaneously transmits the conductivity-time spectrum to the monitoring platform through the wireless transmission device.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a system for testing the release control performance of solid lipid nanoparticles, which utilizes an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device and a monitoring platform to carry out real-time and efficient monitoring on the release performance of the solid lipid nanoparticles, wherein during testing, sodium chloride solution is wrapped in a lipoid core to prepare the solid lipid nanoparticles at a preset temperature, the solid lipid nanoparticles are placed in phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolving process of the solid lipid nanoparticles, the image acquisition device is used for acquiring image information during the dissolving process of the solid lipid nanoparticles, the conductivity sensor is used for detecting a conductivity signal of phosphate solution during the dissolving process of the solid lipid nanoparticles, the image acquisition device transmits the acquired image information of the solid lipid nanoparticle dissolving process to the image processing module for image processing, the image processing module transmits the processed image to the central processing device, the conductivity sensor transmits the collected conductivity signal to the signal processing circuit for signal processing, the signal processing circuit transmits the processed signal to the central processing device, the central processing device transmits the received image information to the display device for display, the central processing device transmits the received image information to the monitoring platform through the wireless transmission device, the central processing device converts the received conductivity signal into a conductivity value, and drawing a conductivity-time spectrum, transmitting the conductivity-time spectrum to a display device for displaying, and transmitting the conductivity-time spectrum to a monitoring platform through a wireless transmission device.
(2) The invention also provides a system for testing the controlled release performance of solid lipid nanoparticles, which is characterized in that signals acquired by a conductivity sensor are weak current signals, so that a signal amplification unit amplifies the current I0 output by the conductivity sensor through an integrated operational amplifier A1-A2, a capacitor C1-C4, a triode VT1-VT4 and a resistor R1-R10, and the signal amplification unit consisting of the integrated operational amplifier A1-A2, the capacitor C1-C4, the triode VT1-VT4 and the resistor R1-R10 only has drift of 1.25 muV/DEG C, drift within 2 muV, bias current of 100pA and noise of 2.25nV within a broadband from 0.1Hz to 10 Hz. The signal filtering unit uses resistors R11-R20, capacitors C5-C11 and an integrated operational amplifier A3-A6 to filter the amplified electric signals, so that the accuracy of conductivity detection is improved.
(3) According to the solid lipid nanoparticle controlled release performance test system provided by the invention, the image processing module sequentially performs image filtering, image smoothing and image enhancement on the acquired image, so that the image information of the image acquisition device can be efficiently and quickly extracted, the identification precision of the image in the solid lipid nanoparticle dissolving process can be improved, and the occurrence of misjudgment conditions can be effectively reduced.
Drawings
FIG. 1 is a functional diagram of a system for testing the controlled release properties of solid lipid nanoparticles according to the present invention;
FIG. 2 is a functional diagram of an image processing module according to the present invention;
FIG. 3 is a waveform diagram of conductivity-time spectrum of the controlled release performance test of solid lipid nanoparticles of the present invention;
fig. 4 is a circuit diagram of a signal processing circuit of the present invention.
Detailed Description
The solid lipid nanoparticle controlled release performance test system provided by the invention is described in detail below with reference to the accompanying drawings and examples.
As shown in fig. 1, the system for testing the controlled release performance of solid lipid nanoparticles provided by the present invention includes an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device, and a monitoring platform.
The output end of the image acquisition device is connected with the input end of the image processing module, the output end of the conductivity sensor is connected with the input end of the signal processing circuit, the output end of the image processing module is connected with the input end of the central processing device, the output end of the signal processing circuit is connected with the input end of the central processing device, the output end of the central processing device is connected with the input end of the display device, and the central processing device is connected with the input end of the monitoring platform through the wireless transmission device.
During testing, at a preset temperature, a sodium chloride solution is wrapped in a lipoid core to prepare solid lipid nanoparticles, the solid lipid nanoparticles are placed in a phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolving process of the solid lipid nanoparticles, an image acquisition device is used for acquiring image information during the dissolving process of the solid lipid nanoparticles, a conductivity sensor is used for detecting conductivity signals of the phosphate solution during the dissolving process of the solid lipid nanoparticles, the image acquisition device transmits the acquired image information during the dissolving process of the solid lipid nanoparticles to an image processing module for image processing, the image processing module transmits the processed images to a central processing device, the conductivity sensor transmits the acquired conductivity signals to a signal processing circuit for signal processing, and the signal processing circuit transmits the processed signals to the central processing device, the central processing device transmits the received conductivity signals and the image information to the display device for displaying, and the central processing device transmits the received conductivity signals and the image information to the monitoring platform through the wireless transmission device.
In the above embodiment, the image acquisition device, the image processing module, the conductivity sensor, the signal processing circuit, the central processing device, the display device, the wireless transmission device and the monitoring platform are used to perform real-time and efficient monitoring on the release performance of the solid lipid nanoparticles, during the test, the sodium chloride solution is wrapped in the lipid core at a preset temperature to prepare the solid lipid nanoparticles, the solid lipid nanoparticles are placed in the phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolution of the solid lipid nanoparticles, the image acquisition device is used to acquire the image information during the dissolution of the solid lipid nanoparticles, the conductivity sensor is used to detect the conductivity signal of the phosphate solution during the dissolution of the solid lipid nanoparticles, and the image acquisition device transmits the acquired image information during the dissolution of the solid lipid nanoparticles to the image processing module for image processing, the image processing module transmits the processed image to the central processing device, the conductivity sensor transmits the collected conductivity signal to the signal processing circuit for signal processing, the signal processing circuit transmits the processed signal to the central processing device, the central processing device transmits the received image information to the display device for display, the central processing device transmits the received image information to the monitoring platform through the wireless transmission device, the central processing device converts the received conductivity signal into a conductivity value, draws a conductivity-time spectrum, transmits the conductivity-time spectrum to the display device for display, and transmits the conductivity-time spectrum to the monitoring platform through the wireless transmission device.
The medium for the release performance test is phosphate buffer solution with pH6.8 (containing 0.5% Tween80), the volume of the medium is 250mL, the temperature of the medium is (37 +/-0.5) DEG C, sodium chloride solution is wrapped in a lipoid core to prepare solid lipid nanoparticles, the solid lipid nanoparticles are placed in phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the conductivity of the phosphate solution is tested within 24h by using a conductivity sensor, and a conductivity-time spectrum is drawn, as shown in FIG. 3.
As shown in fig. 2, the image acquisition device is configured to acquire image information of a solid lipid nanoparticle dissolution process, the image acquisition device transmits the acquired image information of the solid lipid nanoparticle dissolution process to the image processing module for image processing, and the image processing module includes an image filtering unit, an image smoothing unit, and an image enhancement unit.
The output end of the image acquisition device is connected with the input end of the image filtering unit, the output end of the image filtering unit is connected with the input end of the image smoothing unit, the output end of the image smoothing unit is connected with the input end of the image enhancement unit, and the output end of the image enhancement unit is connected with the input end of the central processing unit.
In the above embodiment, the image processing module sequentially performs image filtering, image smoothing and image enhancement on the acquired image, so that the image information of the image acquisition device can be efficiently and quickly extracted, the identification precision of the image in the solid lipid nanoparticle dissolving process can be improved, and the occurrence of misjudgment can be effectively reduced.
Specifically, the image transmitted from the image acquisition device to the image processing module is defined as a two-dimensional function f (x, y), where x and y are spatial coordinates, the image filtering unit performs image filtering processing on the two-dimensional function f (x, y), the two-dimensional function of the image after the image filtering processing is g (x, y), where σ is a filtering parameter, and if the filtering effect is adjusted by σ, then,
g(x，y)＝f(x，y)·G(x，y)。
specifically, the image smoothing unit performs image smoothing processing on an image two-dimensional function g (x, y), where the image two-dimensional function after the image smoothing processing is h (x, y), and where the smoothing function is q (x, y), there are,
h(x，y)＝q(x，y)*g(x，y)；
wherein, the symbol is convolution symbol, gamma is self-defined adjustable constant, and the smooth function is controlled by gamma.
Specifically, the image enhancement unit performs image enhancement processing on an image two-dimensional function h (x, y), and the image two-dimensional function after the image enhancement processing is k (x, y), then there are,
the image enhancement unit transmits the image two-dimensional function k (x, y) to the central processing device.
Researchers can know the dissolving process of the solid lipid nanoparticles at any time through image information displayed by the display device and the monitoring platform.
Specifically, the conductivity sensor is used for detecting conductivity signals of a phosphate solution in a dissolving process of solid lipid nanoparticles, the conductivity sensor transmits the collected conductivity signals to the signal processing circuit for signal processing, the signal processing circuit sequentially amplifies and filters the received conductivity signals, the signal processing circuit transmits the processed signals to the central processing device, the central processing device transmits the received conductivity signals to the display device for display, and the central processing device transmits the received conductivity signals to the monitoring platform through the wireless transmission device.
As shown in fig. 4, the conductivity sensor is used for collecting a conductivity signal of a phosphate solution during a dissolution process of the solid lipid nanoparticles, the conductivity sensor converts the collected conductivity signal into a current signal I0 and transmits the current signal I0 to the signal processing circuit, V1 is a voltage signal processed by the signal processing circuit, the signal processing circuit includes a signal amplifying unit and a signal filtering unit, an output end of the conductivity sensor is connected with an input end of the signal amplifying unit, an output end of the signal amplifying unit is connected with an input end of the signal filtering unit, and an output end of the signal filtering unit is connected with an input end of the central processing unit.
Specifically, the signal amplification unit comprises an integrated operational amplifier A1-A2, a capacitor C1-C4, a triode VT1-VT4 and a resistor R1-R10.
Wherein, the output end of the conductivity sensor is connected with one end of a resistor R1, the other end of a resistor R1 is connected with the inverting input end of an integrated operational amplifier A1, the non-inverting input end of the integrated operational amplifier A1 is grounded, the other end of the resistor R1 is connected with one end of a capacitor C1, one end of the capacitor C2 connected with the resistor R2 in parallel is connected with the other end of a resistor R2, the other end of the capacitor C2 connected with the resistor R2 in parallel is connected with a signal filtering unit, the other end of a capacitor C1 is connected with the output end of the integrated operational amplifier A1, the output end of the integrated operational amplifier A1 is connected with the input end of the integrated operational amplifier A2, one end of a capacitor C3 is grounded, the other end of a capacitor C3 is connected with a +15V power supply, one end of the capacitor C4 is grounded, the other end of a capacitor C4 is connected with a-15V power supply, the other end of a capacitor C4 is also connected with one end of a resistor R4, the other end of the resistor R4 is connected with the V-end of the integrated operational amplifier A2, the other end of the resistor R4 is further connected with a base of a triode VT4, one end of a resistor R3 is connected with a V + end of the integrated operational amplifier A2, one end of a resistor R3 is connected with a base of a triode VT3, one end of a resistor R3 is further connected with a collector of a triode VT1, the other end of a resistor R3 is connected with a +15V power supply, one end of a resistor R10 is connected with a collector of a triode VT2, a collector of the triode VT2 is further connected with a-15V power supply, the other end of a resistor R10 is connected with an emitter of a triode VT4, one end of a resistor R9 is connected with a base of a triode VT2, the other end of a resistor R9 is connected with the other end of a resistor R10, a collector of a triode VT2 is connected with a base of a triode VT4, one end of the resistor R8 is grounded, the other end of the resistor R8 is connected with an output end of the integrated operational amplifier A2, the other end of the resistor R8 is further connected with one end of a resistor R7, and the other end of the resistor R7 is connected with a collector 4, the collector of the triode VT4 is connected with the collector of the triode VT3, the base of the triode VT3 is connected with the collector of the triode VT1, one end of the resistor R6 is connected with the base of the triode VT1, the other end of the resistor R6 is connected with the collector of the triode VT3, one end of the resistor R5 is connected with the collector of the triode VT1, and the other end of the resistor R5 is connected with the other end of the resistor R6.
Specifically, the signal filtering unit comprises resistors R11-R20, capacitors C5-C11 and an integrated operational amplifier A3-A6.
Wherein, the output end of the signal amplifying unit is connected with one end of a resistor R11, the other end of a resistor R11 is connected with one end of a capacitor C5, one end of a resistor R15 is grounded, the other end of a resistor R15 is connected with one end of a resistor R14, the other end of a resistor R15 is connected with the non-inverting input end of an integrated operational amplifier A3, the other end of a resistor R14 is connected with one end of a resistor R13, the other end of a resistor R14 is also connected with the output end of an integrated operational amplifier A4, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A3, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A4, the other end of a resistor R13 is also connected with one end of a capacitor C7, the other end of a capacitor C7 is connected with the output end of an integrated operational amplifier A3, the other end of a capacitor C7 is connected with one end of a resistor R12, the other end of a resistor R12 is connected with one end of a capacitor C6, the non-inverting input end of a resistor R4 is also connected with the input end of an integrated operational amplifier R12, the other end of the capacitor C6 is connected with the other end of the capacitor C5, the other end of the capacitor C5 is further connected with one end of the capacitor C8, one end of the resistor R19 is grounded, the other end of the resistor R19 is connected with one end of the resistor R18, the other end of the resistor R19 is connected with the non-inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R18 is connected with one end of the resistor R17, the other end of the resistor R18 is further connected with the output terminal of the integrated operational amplifier a6, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier a6, the other end of the resistor R17 is further connected with one end of the capacitor C10, the other end of the capacitor C10 is connected with the output terminal of the integrated operational amplifier A5, the other end of the capacitor C10 is connected with one end of the resistor R16, the other end of the resistor R16 is connected with the non-inverting input terminal of the capacitor C9, the integrated operational amplifier R16 is further connected with the non-inverting input terminal 6 of the integrated operational amplifier a6, the other end of the capacitor C9 is connected with the other end of the capacitor C8, the other end of the capacitor C8 is further connected with one end of the capacitor C11, one end of the resistor R20 is grounded, the other end of the resistor R20 is connected with the other end of the capacitor C11, the other end of the resistor R20 is connected with the input end of the central processing unit, and the signal filtering unit transmits the voltage signal V1 to the ADC port of the central processing unit.
In the above embodiment, the noise of the signal processing circuit is within 2.25nV, the drift is 1.25 μ V/° c, the types of the integrated operational amplifiers a1 are all LT1056, the type of the integrated operational amplifier a2 is LT1010, the types of the integrated operational amplifiers A3-a6 are LT1192, the types of the triodes VT1 are all 2N3906, the types of the triodes VT2 are all 2N3904, the types of the triodes VT3 are all MJE2955, and the types of the triodes VT4 are all MJE 3055.
In the signal amplifying unit, the resistance of the resistor R1 is 10k Ω, the resistance of the resistor R2 is 10k Ω, the resistance of the resistor R3 is 33 Ω, the resistance of the resistor R4 is 33 Ω, the resistance of the resistor R5 is 0.18 Ω, the resistance of the resistor R6 is 1k Ω, the resistance of the resistor R7 is 100 Ω, the resistance of the resistor R8 is 100 Ω, the resistance of the resistor R9 is 1k Ω, the resistance of the resistor R10 is 0.18 Ω, the capacitance of the capacitor C1 is 22 μ F, the capacitance of the capacitor C2 is 15pF, the capacitance of the capacitor C3 is 22 μ F, and the capacitance of the capacitor C4 is 22 μ F.
Because the signal collected by the sensor is weak and is easily covered/influenced by noise, the circuit structure of the signal amplification unit provided by the embodiment provides noise resistance, the output power of the integrated operational amplifier A2 is rapidly increased, the effect of amplifying the signal collected by the sensor is better, and the problem of low collection precision of the sensor in the prior art is solved.
The resistor R3 and the resistor R4 collect power supply signals of the integrated operational amplifier A2, and the load of the integrated operational amplifier A2 adopts the grounded resistor R8. The triodes VT3 and VT4 are biased by voltage drop on the resistor R3 and the resistor R4, in addition, a closed feedback loop is formed by the resistor R7 to ensure stable output of signal amplification signals, the signals are directly fed back to the integrated operational amplifier A1 through the resistor R2 to control amplification, and the triodes VT1 and VT2 sense the voltage drop on the resistors R5 and R10, so that noise signals can be effectively inhibited.
The stability of the integrated operational amplifier a1 is ensured by the capacitor C1 causing it to roll off, and the feedback capacitor of the capacitor C2 trims the edge response, and the transistor used in the signal amplification unit in this embodiment has a low frequency response, so that it is not necessary to consider performing additional frequency compensation in the signal amplification unit.
The output voltage signal of the signal amplification unit is V01.
In the signal filtering unit, the resistance values of the resistors R15-R24 and the capacitance values of the capacitors C10-C11 are set according to the filtering requirement.
In this embodiment, a set of values of the resistances of the resistors R11 to R20 and the capacitances of the capacitors C5 to C11 is preferred, where the resistance of the resistor R11 is 100k Ω, the resistance of the resistor R12 is 66.5k Ω, the resistance of the resistor R13 is 66.5k Ω, the resistance of the resistor R14 is 66.5k Ω, the resistance of the resistor R15 is 66.5k Ω, the resistance of the resistor R16 is 75k Ω, the resistance of the resistor R17 is 75k Ω, the resistance of the resistor R18 is 75k Ω, the resistance of the resistor R19 is 75k Ω, the resistance of the resistor R20 is 100k Ω, the capacitance of the capacitor C5 is 5.161nF, the capacitance of the capacitor C6 is 35.05nF, the capacitance of the capacitor C7 is 10nF, the capacitance of the capacitor C8 is 3.251nF, the capacitance of the capacitor C9 is 12.03nF, the capacitance of the capacitor C10 is 10nF, and the capacitance of the capacitor C599 is 28 nF.
Because the signals collected by the conductivity sensor are weak current signals, the signal amplification unit amplifies the current I0 output by the conductivity sensor through the integrated operational amplifier A1-A2, the capacitor C1-C4, the triode VT1-VT4 and the resistor R1-R10, and the signal amplification unit consisting of the integrated operational amplifier A1-A2, the capacitor C1-C4, the triode VT1-VT4 and the resistor R1-R10 has drift of only 1.25 muV/DEG C, drift within 2 muV, bias current of 100pA and noise of 2.25nV within a 0.1Hz to 10Hz broadband. The signal filtering unit uses resistors R11-R20, capacitors C5-C11 and an integrated operational amplifier A3-A6 to filter the amplified electric signals, so that the accuracy of conductivity detection is improved.
Specifically, the central processing unit converts the received conductivity signal into a conductivity value, draws a conductivity-time spectrum, transmits the conductivity-time spectrum to the display device for display, and transmits the conductivity-time spectrum to the monitoring platform through the wireless transmission device.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and are not limited. Although the present invention has been described in detail with reference to the embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (3)
1. A system for testing the controlled release performance of solid lipid nanoparticles is characterized by comprising an image acquisition device, an image processing module, a conductivity sensor, a signal processing circuit, a central processing device, a display device, a wireless transmission device and a monitoring platform;
the output end of the image acquisition device is connected with the input end of the image processing module, the output end of the conductivity sensor is connected with the input end of the signal processing circuit, the output end of the image processing module is connected with the input end of the central processing device, the output end of the signal processing circuit is connected with the input end of the central processing device, the output end of the central processing device is connected with the input end of the display device, and the central processing device is connected with the input end of the monitoring platform through the wireless transmission device;
during testing, at a preset temperature, a sodium chloride solution is wrapped in a lipoid core to prepare solid lipid nanoparticles, the solid lipid nanoparticles are placed in a phosphate solution, the solid lipid nanoparticles are dissolved in the phosphate solution, the sodium chloride solution is released during the dissolving process of the solid lipid nanoparticles, the image acquisition device is used for acquiring image information of the dissolving process of the solid lipid nanoparticles, the conductivity sensor is used for detecting a conductivity signal of the phosphate solution during the dissolving process of the solid lipid nanoparticles, the image acquisition device transmits the acquired image information of the dissolving process of the solid lipid nanoparticles to the image processing module for image processing, the image processing module transmits a processed image to the central processing device, and the conductivity sensor transmits the acquired conductivity signal to the signal processing circuit for signal processing, the signal processing circuit transmits the processed signals to the central processing device, the central processing device transmits the received conductivity signals and the image information to the display device for display, and the central processing device transmits the received conductivity signals and the image information to the monitoring platform through the wireless transmission device;
the image acquisition device is used for acquiring image information of the solid lipid nanoparticle dissolution process, the image acquisition device transmits the acquired image information of the solid lipid nanoparticle dissolution process to the image processing module for image processing, and the image processing module comprises an image filtering unit, an image smoothing unit and an image enhancement unit;
the output end of the image acquisition device is connected with the input end of the image filtering unit, the output end of the image filtering unit is connected with the input end of the image smoothing unit, the output end of the image smoothing unit is connected with the input end of the image enhancement unit, and the output end of the image enhancement unit is connected with the input end of the central processing device;
the image transmitted to the image processing module by the image acquisition device is defined as a two-dimensional function f (x, y), wherein x and y are space coordinates, the image filtering unit performs image filtering processing on the two-dimensional function f (x, y), and the two-dimensional function of the image after the image filtering processing is g (x, y), wherein,
for the filtering parameters, the filtering effect is passed
The adjustment is carried out, if at all,
the image smoothing unit performs image smoothing on an image two-dimensional function g (x, y), wherein the image two-dimensional function after the image smoothing is h (x, y), and q (x, y) is used as a smoothing function,
where ﹡ is a convolution symbol,
for self-defining adjustable constants, smoothing is effected by
To control;
the image enhancement unit carries out image enhancement processing on the two-dimensional image function h (x, y), if the two-dimensional image function after the image enhancement processing is k (x, y),
the image enhancement unit transmits the image two-dimensional function k (x, y) to the central processing device;
the conductivity sensor is used for acquiring a conductivity signal of a phosphate solution in the dissolving process of the solid lipid nanoparticles, the conductivity sensor converts the acquired conductivity signal into a current signal I0 and transmits the current signal I0 to the signal processing circuit, V1 is a voltage signal processed by the signal processing circuit, the signal processing circuit comprises a signal amplification unit and a signal filtering unit, the output end of the conductivity sensor is connected with the input end of the signal amplification unit, the output end of the signal amplification unit is connected with the input end of the signal filtering unit, and the output end of the signal filtering unit is connected with the input end of the central processing device;
the signal amplification unit comprises an integrated operational amplifier A1-A2, a capacitor C1-C4, a triode VT1-VT4 and a resistor R1-R10;
wherein, the output end of the conductivity sensor is connected with one end of a resistor R1, the other end of a resistor R1 is connected with the inverting input end of an integrated operational amplifier A1, the non-inverting input end of the integrated operational amplifier A1 is grounded, the other end of a resistor R1 is connected with one end of a capacitor C1, one end of the parallel connection of the capacitor C2 and the resistor R2 is connected with the other end of a resistor R2, the other end of the parallel connection of the capacitor C2 and the resistor R2 is connected with the signal filtering unit, the other end of a capacitor C1 is connected with the output end of the integrated operational amplifier A1, the output end of the integrated operational amplifier A1 is connected with the input end of the integrated operational amplifier A2, one end of a capacitor C3 is grounded, the other end of the capacitor C3 is connected with a +15V power supply, one end of a capacitor C4 is grounded, the other end of the capacitor C4 is connected with a-15V power supply, the other end of a capacitor C4 is also connected with one end of a resistor R4, the other end of the resistor R4 is connected with the V-end of the integrated operational amplifier A2, the other end of the resistor R4 is further connected with a base of a triode VT4, one end of a resistor R3 is connected with a V + end of the integrated operational amplifier A2, one end of a resistor R3 is connected with a base of a triode VT3, one end of a resistor R3 is further connected with a collector of a triode VT1, the other end of a resistor R3 is connected with a +15V power supply, one end of a resistor R10 is connected with a collector of a triode VT2, a collector of the triode VT2 is further connected with a-15V power supply, the other end of a resistor R10 is connected with an emitter of a triode VT4, one end of a resistor R9 is connected with a base of a triode VT2, the other end of a resistor R9 is connected with the other end of a resistor R10, a collector of a triode VT2 is connected with a base of a triode VT4, one end of the resistor R8 is grounded, the other end of the resistor R8 is connected with an output end of the integrated operational amplifier A2, the other end of the resistor R8 is further connected with one end of a resistor R7, and the other end of the resistor R7 is connected with a collector 4, the collector of the triode VT4 is connected with the collector of the triode VT3, the base of the triode VT3 is connected with the collector of the triode VT1, one end of the resistor R6 is connected with the base of the triode VT1, the other end of the resistor R6 is connected with the collector of the triode VT3, one end of the resistor R5 is connected with the collector of the triode VT1, and the other end of the resistor R5 is connected with the other end of the resistor R6;
the signal filtering unit comprises resistors R11-R20, capacitors C5-C11 and an integrated operational amplifier A3-A6;
wherein, the output end of the signal amplification unit is connected with one end of a resistor R11, the other end of the resistor R11 is connected with one end of a capacitor C5, one end of a resistor R15 is grounded, the other end of a resistor R15 is connected with one end of a resistor R14, the other end of a resistor R15 is connected with the non-inverting input end of an integrated operational amplifier A3, the other end of a resistor R14 is connected with one end of a resistor R13, the other end of a resistor R14 is also connected with the output end of an integrated operational amplifier A4, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A3, the other end of a resistor R13 is connected with the inverting input end of an integrated operational amplifier A4, the other end of a resistor R13 is also connected with one end of a capacitor C7, the other end of a capacitor C7 is connected with the output end of an integrated operational amplifier A3, the other end of a capacitor C7 is connected with one end of a resistor R12, the other end of a resistor R12 is connected with one end of a capacitor C6, the other end of a resistor R12 is also connected with the non-inverting input end of an integrated operational amplifier R4, the other end of the capacitor C6 is connected with the other end of the capacitor C5, the other end of the capacitor C5 is further connected with one end of the capacitor C8, one end of the resistor R19 is grounded, the other end of the resistor R19 is connected with one end of the resistor R18, the other end of the resistor R19 is connected with the non-inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R18 is connected with one end of the resistor R17, the other end of the resistor R18 is further connected with the output terminal of the integrated operational amplifier a6, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier A5, the other end of the resistor R17 is connected with the inverting input terminal of the integrated operational amplifier a6, the other end of the resistor R17 is further connected with one end of the capacitor C10, the other end of the capacitor C10 is connected with the output terminal of the integrated operational amplifier A5, the other end of the capacitor C10 is connected with one end of the resistor R16, the other end of the resistor R16 is connected with the non-inverting input terminal of the capacitor C9, the integrated operational amplifier R16 is further connected with the non-inverting input terminal 6 of the integrated operational amplifier a6, the other end of the capacitor C9 is connected with the other end of the capacitor C8, the other end of the capacitor C8 is further connected with one end of the capacitor C11, one end of the resistor R20 is grounded, the other end of the resistor R20 is connected with the other end of the capacitor C11, the other end of the resistor R20 is connected with the input end of the central processing unit, and the signal filtering unit transmits the voltage signal V1 to the ADC port of the central processing unit.
2. The system for testing the controlled release performance of the solid lipid nanoparticles according to claim 1, wherein the conductivity sensor is configured to detect a conductivity signal of a phosphate solution during the dissolution process of the solid lipid nanoparticles, the conductivity sensor transmits the collected conductivity signal to the signal processing circuit for signal processing, the signal processing circuit sequentially performs signal amplification and signal filtering on the received conductivity signal, the signal processing circuit transmits the processed signal to the central processing unit, the central processing unit transmits the received conductivity signal to the display device for display, and the central processing unit transmits the received conductivity signal to the monitoring platform through the wireless transmission device.
3. The system for testing the controlled release performance of solid lipid nanoparticles of claim 1, wherein the central processing unit converts the received conductivity signal into a conductivity value, and plots the conductivity value to a conductivity-time spectrum, and transmits the conductivity-time spectrum to the display unit for displaying, and simultaneously transmits the conductivity-time spectrum to the monitoring platform through the wireless transmission unit.
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