CN113633261A - Multichannel in-vivo pharmacokinetic analysis system based on fluorescence monitoring - Google Patents
Multichannel in-vivo pharmacokinetic analysis system based on fluorescence monitoring Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4866—Evaluating metabolism
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- A—HUMAN NECESSITIES
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- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
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- A—HUMAN NECESSITIES
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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- A—HUMAN NECESSITIES
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
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- A—HUMAN NECESSITIES
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
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- A—HUMAN NECESSITIES
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
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- A—HUMAN NECESSITIES
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- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
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- A—HUMAN NECESSITIES
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Abstract
The invention discloses a multi-channel in-vivo drug-induced analysis system based on fluorescence monitoring, which comprises: the system comprises a light source, a multi-path optical switch, a fluorescence spectrometer, a Y-shaped optical fiber probe group, a control circuit, an operating platform, a two-channel respiratory anesthesia machine and an upper computer. The invention can realize multi-channel real-time in-vivo monitoring and obtain more accurate biological data relative to in-vitro data; the optical fiber arrangement is designed according to a spectrometer slit, and the time-sharing multiplexing is carried out on the spectrometer by utilizing the switching of the optical switch, so that the monitoring of different tissues, organs, blood vessels and other parts of the small animal by six channels is realized; different physiological pharmacokinetic models are established on the upper computer aiming at the in-vivo data of a plurality of tissues for analysis, more accurate data is provided for new drug metabolism, and the clinical transformation and application of the new drug metabolism are promoted.
Description
Technical Field
The invention relates to the technical field of nano-drug medical detection, in particular to a multi-channel in-vivo drug-induced analysis system based on fluorescence monitoring.
Background
The transportation, distribution, release and the like of the nano-drug in vivo are closely related to the curative effect of the nano-drug, and are the key for evaluating the clinical transformation of the nano-drug. In recent years, in vivo pharmacokinetic studies of small animals by optical microscopy have become a popular topic for evaluating the potency of nano-drugs. The characteristics of high specific surface area, easy surface modification and the like of the nano-drug endow the nano-drug with various higher biological activities, including biological membrane barrier penetrability, tissue distribution selectivity, drug release controllability, membrane transport mechanism transition property and the like. Compared with the traditional medicine, the nano medicine has the advantages of long plasma half-life period, low clearance rate, targeted medicine delivery to pathological tissues and the like, and can effectively improve the treatment effect of the medicine and reduce toxic and side effects. Meanwhile, the change of the transmembrane mechanism can increase the permeability of the drug to a biological membrane, is beneficial to the absorption of drug tissues and plays the drug effect in cells, and further improves the treatment effect of drug-resistant diseases.
According to research statistics, however, only a very small amount of nano-drugs eventually enter clinical use compared to a large number of basic studies. In the rejected drugs in clinical research, about 40% of candidate drugs can not enter the clinic finally because the pharmacokinetic behavior does not meet the treatment requirement, and the drug property evaluation of the nano-drug, such as effectiveness, safety and quality controllability, is always the bottleneck problem limiting the conversion of the nano-drug to the clinic. The basic research of the kinetics characteristics in the clinical precursor of the nano-drug not only needs to examine the dynamic distribution characteristics in blood and blood in blood vessels, but also needs to reveal the dynamic distribution characteristics of the nano-drug in the accumulation of main metabolic organs (liver, kidney, etc.), the injury of organ tissues and the tumor tissues of target tissues. At present, the early preparation work of drug analysis is complex and tedious, a large number of small animals need to be dosed at the same time in one experiment, then, the plasma collection of the animals and the tissue homogenization of each part need to be carried out in batches in a specific time to detect the drug dosage contained in the animals, which is a huge and time-consuming work, and the problems of time difference, individual difference among the animals, in-vitro data collection and the like exist. The nuclide detection commonly used in the volume data analysis has the characteristics of low resolution, incapability of acquiring accurate data only by observing the aggregation state, and the like.
Disclosure of Invention
The invention aims to solve the technical problem of providing a multi-channel in-vivo drug-based analysis system based on fluorescence monitoring, which realizes multi-channel monitoring while ensuring the monitoring speed and provides more accurate and comprehensive in-vivo data for the metabolism of nano-drugs.
In order to solve the above technical problems, the present invention provides a multi-channel in vivo drug-induced analysis system based on fluorescence monitoring, comprising: the system comprises a light source, a multi-path optical switch, a fluorescence spectrometer, a Y-shaped optical fiber probe group, a control circuit, an operating platform, a two-channel anesthesia machine and an upper computer; the Y-shaped optical fiber probe group and the two-channel respiratory anesthesia machine are fixed on the operation platform, the mask and the experimental animal are connected, under the control of the upper computer and the control circuit, excitation light generated at a light source is transmitted to the Y-shaped optical fiber probe group through the multi-path optical switch, a medicine in the experimental animal is excited to generate fluorescence, the fluorescence is received and transmitted to the fluorescence spectrometer by the Y-shaped optical fiber probe group for processing, data of the fluorescence spectrometer is transmitted to the upper computer for further processing and displaying, the distribution conditions of the nano-medicine at the parts such as blood, tissues, organs and the like are reflected, and the action mechanism of the nano-medicine is revealed.
Preferably, the light source is a single-wavelength laser light source or a high-pressure mercury lamp equipped with a corresponding wavelength filter.
Preferably, the number of acquisition channels of the fluorescence spectrometer is from 1 channel up to 6 channels.
Preferably, the multi-channel optical switch performs switching of the number of channels from 2 channels to a maximum of 6 channels.
Preferably, the multi-path optical switch controls the optical path switching mode by a stepping motor, the control mode is TTL, the multi-path optical switch has the functions of controlling the optical path and converting the optical path, and the minimum switching time of adjacent optical paths is 80 ms.
Preferably, in the Y-shaped optical fiber probe group, an excitation optical fiber and a receiving optical fiber are arranged side by side at the probe end of each optical fiber probe group; the excitation optical fibers are respectively coupled with corresponding channels of the mechanical optical switch and used for transmitting excitation light sources; the receiving optical fibers are integrated into a bundle and collected into a receiving optical path to be connected with the spectrometer, and the optical fiber bundles are linearly arranged and matched with the shape of a slit at the entrance of the spectrometer; the core diameter of a representative optical fiber is 135 μm, the total length of the receiving optical fiber linear arrangement is 900 μm, the slit length is 1mm, and the width is 200 μm.
Preferably, the control circuit board comprises a voltage reduction module for reducing the voltage of the DC12V to DC5V and 3.3V; the microcontroller module is used for processing data by adopting a 32-bit microprocessor of a Cortex-M4 kernel; the TTL communication module is communicated with the optical switch; and the control circuit is used for realizing communication with the optical switch to control on-off switching of the optical switch.
The invention has the beneficial effects that: the multichannel real-time in-vivo monitoring can be realized, and more accurate biological data relative to in-vitro data can be obtained; the optical fiber arrangement is designed according to a spectrometer slit, and the time-sharing multiplexing is carried out on the spectrometer by utilizing the switching of the optical switch, so that the monitoring of different tissues, organs, blood vessels and other parts of the small animal by six channels is realized; different physiological pharmacokinetic models are established on the upper computer aiming at the in-vivo data of a plurality of tissues for analysis, more accurate data is provided for new drug metabolism, and the clinical transformation and application of the new drug metabolism are promoted.
Drawings
FIG. 1 is a schematic diagram of the system of the present invention.
Fig. 2 is a schematic structural diagram of the fiber probe set of the present invention.
FIG. 3 is a cross-sectional view of a fiber optic probe of the present invention.
FIG. 4 is a cross-sectional view of a fluorescence receiving fiber according to the present invention.
FIG. 5 is a cross-sectional view of a fluorescence excitation fiber according to the present invention.
Fig. 6 is a schematic diagram of the optical switch circuit of the present invention.
Wherein, 1, an upper computer; 2. a control circuit; 3. a light source; 4. a multi-path optical switch; 5. a fluorescence spectrometer; 6. a Y-shaped fiber probe group; 7. an operating platform; 8. a two-channel respiratory anesthesia machine; 9. a fiber optic probe; 10. a handle; 11. plastic-coated flexible pipes; 12. a beam splitter; 13. a shunt fluorescence receiving fiber; 14. a beam combiner; 15. a fluorescence receiving fiber; 16. a fluorescence excitation optical fiber; 17. a laser light source; 18. a first optical path; 19. a second optical path; 20. a third optical path; 21. a fourth optical path; 22. a fifth optical path; 23. and a sixth optical path.
Detailed Description
As shown in fig. 1, a multi-channel in vivo drug-induced analysis system based on fluorescence monitoring comprises: the system comprises a multi-wavelength laser light source 3, a multi-path optical switch 4, a Y-shaped optical fiber probe group 6, a fluorescence spectrometer 5, a control circuit 2, an operating platform 7, a two-channel anesthesia machine 8 and an upper computer 1. The optical fiber probe and the anesthesia machine are fixed on the operating platform 7 and are connected with the mask and the experimental animal, under the control of the upper computer 1 and the control circuit 2, the excitation light generated by the light source 3 is transmitted to the optical fiber probe group 6 through the optical switch 4 to excite the drug in the experimental animal to generate fluorescence, the fluorescence is received by the optical fiber probe and is transmitted to the spectrometer 5, and the spectrometer data is transmitted to the upper computer 1 for further processing and displaying.
The laser light source 3 is a multi-wavelength laser and can be used for a wider fluorescent dye spectrum, so that the selection range of the fluorescent dye is widened; six channels of the multi-path optical switch 4 are coupled with six excitation optical fibers, and different optical paths are controlled to select corresponding optical fiber probe groups 6 to transmit laser; the fiber core of the excitation fiber and the fiber core of the receiving fiber are arranged in parallel in the fiber probe, and the six receiving fibers are integrated into a bundle and collected into a receiving light path to be connected with the spectrometer 5; the integrated receiving optical fibers are arranged in a linear mode, the shape of the slit at the entrance of the spectrometer is matched, and the time-sharing multiplexing spectrometer 5 is used for effectively collecting the fluorescence data of the six channels; the spectrometer is an ocean optical high-sensitivity fluorescence spectrometer, and the high performance of the spectrometer provides higher accuracy for fluorescence detection; the two-channel anesthesia machine 8 ensures that the small animal on the operation platform 7 is in an anesthesia state with stable respiration for a long time; the software of the upper computer 1 selects different channels according to requirements to control signal acquisition, analyzes the acquired data in a physiological pharmacokinetic model, simultaneously displays the fluorescence information of the nano-drugs of each channel, reflects the distribution condition of the nano-drugs in blood, tissues, organs and other parts, and reveals the action mechanism of the nano-drugs.
Fig. 2 is a schematic structural diagram of a fiber-optic probe group according to the present invention. The system selects 6 groups of Y-shaped optical fiber probe groups to transmit excitation light and fluorescence, and comprises an optical fiber probe 9, a handle 10, a plastic-coated hose 11, a beam splitter 12, a shunt fluorescence receiving optical fiber 13, a beam combiner 14, a fluorescence receiving optical fiber 15 and a fluorescence excitation optical fiber 16. The six paths of laser are transmitted to the corresponding optical fiber probes 9 through the fluorescence excitation optical fibers 16 under the control of the optical switch 4. The fluorescence of the drug is excited by the corresponding optical fiber probe 9, and a fluorescence signal is collected. The six fluorescence receiving optical fibers 13 are combined into a receiving optical fiber 15 at the beam combiner 14, and the slit of the spectrometer is adapted to transmit the collected signals into the spectrometer 5.
Fig. 3 is a schematic cross-sectional view of a fiber optic probe according to the present invention. According to the arrangement in the figure, the excitation optical fiber and the receiving optical fiber are arranged side by side for exciting fluorescence and collecting fluorescence signals.
Fig. 4 is a schematic cross-sectional view of a receiving fiber 15 according to the present invention. The six receiving optical fiber cores are linearly arranged in a line and are suitable for a spectrometer slit.
Fig. 5 is a schematic cross-sectional view of excitation fiber 16 according to the present invention. The inner part is an excitation optical fiber core.
Fig. 6 is a diagram showing an internal optical path of the optical switch according to the present invention. After the laser light of the laser light source 17 enters the optical switch, the six optical paths 18 to 23 are switched back and forth. Six channels of the optical switch are coupled with six excitation fibers. The minimum switching time of the adjacent optical paths is 80ms, and the purpose of simultaneously monitoring six positions is met.
Claims (7)
1. A multi-channel in vivo pharmacokinetic analysis system based on fluorescence monitoring, comprising: the system comprises a light source, a multi-path optical switch, a fluorescence spectrometer, a Y-shaped optical fiber probe group, a control circuit, an operating platform, a two-channel anesthesia machine and an upper computer; the Y-shaped optical fiber probe group and the two-channel respiratory anesthesia machine are fixed on the operation platform, the mask and the experimental animal are connected, under the control of the upper computer and the control circuit, excitation light generated at a light source is transmitted to the Y-shaped optical fiber probe group through the multi-path optical switch, a medicine in the experimental animal is excited to generate fluorescence, the fluorescence is received and transmitted to the fluorescence spectrometer by the Y-shaped optical fiber probe group for processing, data of the fluorescence spectrometer is transmitted to the upper computer for further processing and displaying, the distribution conditions of the nano-medicine at the parts such as blood, tissues, organs and the like are reflected, and the action mechanism of the nano-medicine is revealed.
2. The multi-channel in-vivo pharmacokinetic analysis system based on fluorescence monitoring of claim 1, wherein the light source is a single wavelength laser light source or a high pressure mercury lamp equipped with a corresponding wavelength color filter.
3. The fluorescence monitoring based multichannel in vivo drug analysis system of claim 1, wherein the number of acquisition channels of the fluorescence spectrometer is from 1 channel up to 6 channels.
4. The fluorescence monitoring based multichannel in vivo drug analysis system of claim 1, wherein the multi-channel optical switch performs switching of the number of channels from 2 channels to at most 6 channels.
5. The fluorescence monitoring-based multi-channel in-vivo drug-induced analysis system of claim 1, wherein the multi-channel optical switch is controlled by a stepping motor in a way of switching optical paths, wherein the multi-channel optical switch is TTL and has functions of controlling the optical paths and switching the optical paths, and the minimum switching time of adjacent optical paths is 80 ms.
6. The multi-channel in-vivo pharmacokinetic analysis system based on fluorescence monitoring as claimed in claim 1, wherein, in the Y-shaped optical fiber probe set, an excitation optical fiber and a receiving optical fiber are arranged side by side at each probe end; the excitation optical fibers are respectively coupled with corresponding channels of the mechanical optical switch and used for transmitting excitation light sources; the receiving optical fibers are integrated into a bundle and collected into a receiving optical path to be connected with the spectrometer, and the optical fiber bundles are linearly arranged and matched with the shape of a slit at the entrance of the spectrometer; the core diameter of a representative optical fiber is 135 μm, the total length of the receiving optical fiber linear arrangement is 900 μm, the slit length is 1mm, and the width is 200 μm.
7. The fluorescence monitoring-based multichannel in vivo drug analysis system according to claim 1, wherein the control circuit board comprises a voltage reduction module for reducing DC12V to DC5V and 3.3V; the microcontroller module is used for processing data by adopting a 32-bit microprocessor of a Cortex-M4 kernel; the TTL communication module is communicated with the optical switch; and the control circuit is used for realizing communication with the optical switch to control on-off switching of the optical switch.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6377842B1 (en) * | 1998-09-22 | 2002-04-23 | Aurora Optics, Inc. | Method for quantitative measurement of fluorescent and phosphorescent drugs within tissue utilizing a fiber optic probe |
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| US20090043296A1 (en) * | 2004-06-30 | 2009-02-12 | University Of Rochester | Photodynamic therapy with spatially resolved dual spectroscopic monitoring |
| CN104458587A (en) * | 2014-12-11 | 2015-03-25 | 上海交通大学 | Multichannel unmarked biosensing optical fiber system |
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| CN111795955A (en) * | 2020-06-22 | 2020-10-20 | 天津大学 | Multilayer perception neural network-based fluorescence pharmacokinetic tomography method |
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2021
- 2021-08-11 CN CN202110917877.7A patent/CN113633261A/en active Pending
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| US6377842B1 (en) * | 1998-09-22 | 2002-04-23 | Aurora Optics, Inc. | Method for quantitative measurement of fluorescent and phosphorescent drugs within tissue utilizing a fiber optic probe |
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| US20090043296A1 (en) * | 2004-06-30 | 2009-02-12 | University Of Rochester | Photodynamic therapy with spatially resolved dual spectroscopic monitoring |
| CN104458587A (en) * | 2014-12-11 | 2015-03-25 | 上海交通大学 | Multichannel unmarked biosensing optical fiber system |
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