CN105548102B - Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device - Google Patents

Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device Download PDF

Info

Publication number
CN105548102B
CN105548102B CN201510896712.0A CN201510896712A CN105548102B CN 105548102 B CN105548102 B CN 105548102B CN 201510896712 A CN201510896712 A CN 201510896712A CN 105548102 B CN105548102 B CN 105548102B
Authority
CN
China
Prior art keywords
calcium ion
optoacoustic
signal
fluorescence
software
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201510896712.0A
Other languages
Chinese (zh)
Other versions
CN105548102A (en
Inventor
邢达
覃欢
杨思华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China Normal University
Original Assignee
South China Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by South China Normal University filed Critical South China Normal University
Priority to CN201510896712.0A priority Critical patent/CN105548102B/en
Publication of CN105548102A publication Critical patent/CN105548102A/en
Application granted granted Critical
Publication of CN105548102B publication Critical patent/CN105548102B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6456Spatial resolved fluorescence measurements; Imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/1702Systems in which incident light is modified in accordance with the properties of the material investigated with opto-acoustic detection, e.g. for gases or analysing solids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/1702Systems in which incident light is modified in accordance with the properties of the material investigated with opto-acoustic detection, e.g. for gases or analysing solids
    • G01N2021/1706Systems in which incident light is modified in accordance with the properties of the material investigated with opto-acoustic detection, e.g. for gases or analysing solids in solids

Landscapes

  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Optics & Photonics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

The present invention, which discloses, a kind of utilizes optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device.This method can detect the variation of calcium ion concentration size by the variation of the photoacoustic signal power of detection calcium ion fluorescent.The device includes optoacoustic fluorescence signal excitaton source, bowl-shape hollow focusing ultrasonic detector, photomultiplier tube, reflecting mirror, spectroscope, extender lens group, microcobjective, ultrasonic coupling cup, sample stage, three dimensional scanning platform, optical filter, signal amplifier, binary channels parallel acquisition card, the computer with acquisition control software and image reconstruction software and motor control software.This method and device can realize that the calcium ion concentration of deep tissues monitors;Easy to operate, the sensitivity for monitoring calcium ion fluorescent can reach 0.15 μM, can monitor the variation of deep tissues calcium ion concentration.The present invention can real-time detection deep tissues calcium ion concentration situation of change, thus can be inferred to tissue pathologic change degree by the speed of the variation.

Description

Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device
Technical field
It is the invention belongs to non-destructive testing field of measuring technique, in particular to a kind of to utilize optoacoustic-fluorescence complementary principle depth Layer calcium ion concentration monitoring method and device.
Background technique
Presently mainly the variation of calcium ion concentration is monitored by observing the fluorescence signal of calcium ion fluorescent.However Influence due to biological tissue to fluorescent scattering, the variation of fluorescence imaging method deep layer calcium ion concentration unable to monitor.And optoacoustic Signal (photic ultrasound) is influenced by tissue scatter much smaller than influence suffered by photon, therefore we are by lossless photoacoustic imaging technology It is combined together with deep penetration characteristic in pure optical imagery high sensitivity characteristic and pure ultrasonic imaging, overcomes light scattering limitation, Realize the high-resolution to living body deep tissues, high-contrast image.Calcium ion is that body items physiological activity is indispensable Ion.It maintains normal Nerve conduction for the biotic potential of maintenance cell membrane two sides, maintains normal muscle flexible With diastolic function and nerve, muscle conduction function, very important effect is played.Calcium ion, as in signal transduction pathway First messenger, it is most important for the presynaptic neuron and neuroglia of entire central nervous system.
Summary of the invention
In order to overcome the disadvantages and deficiencies of the prior art, the primary purpose of the present invention is that providing a kind of glimmering using optoacoustic- The deep layer calcium ion concentration monitoring method of light complementarity principle.
Another object of the present invention is to provide utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring dress It sets.
The purpose of the invention is achieved by the following technical solution:
It is a kind of using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method, include the following steps:
(1) using calcium ion fluorescent as optoacoustic calcium ion probe;
Since the fluorescence intensity of calcium ion fluorescent can enhance or weaken with the increase of the concentration of calcium ion.? Optoacoustic, the fluorescence signal generated in same excitation process is shifting, and there is complementary relationships.Therefore, calcium ion fluorescent Photoacoustic signal can with the concentration of calcium ion increase and reduce or enhancing.Therefore, it can be visited by detection calcium ion fluorescence The variation of the photoacoustic signal power of needle detects the variation of calcium ion concentration size.Again because of photoacoustic waves (photoacoustic signal) tissue The influence of scattering is small more than fluorescence, therefore utilizes optoacoustic-fluorescence complementary principle, and the optoacoustic by detecting calcium ion fluorescent is believed It number can monitor the variation of deep tissues calcium ion.
(2) calcium ion fluorescent is injected into the region of quasi- detection;
(3) pulse laser that optoacoustic fluorescence signal excitaton source issues focuses on detection zone after microcobjective, so that Calcium ion fluorescent generates photoacoustic signal and fluorescence signal;
(4) photoacoustic signal is received after passing through ultrasonic coupling liquid by bowl-shape hollow focusing ultrasonic detector, then passes through signal Amplifier amplification;Fluorescence signal is received after spectroscope and optical filter filter by photomultiplier tube;Two paths of signals is by binary channels Parallel acquisition card acquires simultaneously, then data are transmitted and are stored into the computer with acquisition control software and image reconstruction software In;
(5) it is placed on three dimensional scanning platform together with test sample and the ultrasonic coupling cup for holding ultrasonic coupling liquid, by filling There is the three-dimensional of the computer control sample of motor control software mobile;Every photoacoustic signal for having acquired a point, 3-D scanning are flat Platform horizontal direction is orderly moved and is moved a step;After scanning through a plane, platform vertically moves a step again;It is point-by-point to be carried out to sample Scanning, for rebuilding 3-D image;It is final to obtain three-dimensional photoacoustce signal intensity distribution, to obtain calcium ion concentration distribution;
(6) after the photoacoustic signal of calcium ion fluorescent is collected, calcium ion is reconstructed by maximum value projection algorithm and is visited Needle photoacoustce signal intensity distributed image judges that the concentration of calcium ion changes according to photoacoustce signal intensity;
(7) pass through the photoacoustce signal intensity of the calcium ion fluorescent of detection single-point, the real-time monitoring calcium ion concentration Variation.
Calcium ion fluorescent described in step (1) is preferably Rhod-2, but does not limit above-mentioned probe.
The absorption spectrum before and after with calcium binding of calcium ion fluorescent selected in the step (2) becomes without obvious Change.
Optoacoustic fluorescence signal excitaton source described in step (3) is pulse laser, and Output of laser wavelength is according to calcium ion The excitation wavelength of fluorescence probe selects.
Pulse laser described in step (3) be output laser pulse width be nanosecond or picosecond laser, it is defeated Wavelength is 532nm, 675~1000nm, repetition rate 20Hz~10KHz out.
Motor control software described in step (4) is Labview software, and program is voluntarily write.
Ultrasonic coupling liquid described in step (5) is water;
The bowl-shape hollow dominant frequency for focusing ultrasonic detector is 10MHz, hollow focusing probe described in step (5).
Acquisition control software described in step (5) and image reconstruction software are Labview software, and program is voluntarily compiled It writes;
Maximum value projection algorithm described in step (6) is voluntarily write by Matlab software.
Detection single-point described in step (7) utilizes the pulse laser and high sampling rate of high repetition frequency (10KHz) Capture card 200M/s.
It using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring device, is constructed according to the above method.Institute The detection device stated include optoacoustic fluorescence signal excitaton source, bowl-shape hollow focusing ultrasonic detector, photomultiplier tube, reflecting mirror, Spectroscope, extender lens group, microcobjective, ultrasonic coupling cup, sample stage, three dimensional scanning platform, optical filter, signal amplifier, Binary channels parallel acquisition card, the computer with acquisition control software and image reconstruction software and motor control software.
The optoacoustic fluorescence signal excitaton source be output laser pulse width be nanosecond or picosecond pulse laser, It is transmitted light on microcobjective after laser output by reflecting mirror, microcobjective focuses light on sample.
The bowl-shape hollow bowl-shape hollow ultrasonic probe for focusing ultrasonic detector is fixed below microcobjective, makes to show Speck mirror and ultrasonic probe are coaxial, and luminous energy passes through the focal point that probe focuses on ultrasonic probe from the intermediate aperture of probe, realize Light, sound are confocal.The photoacoustic signal that excitation generates is received by ultrasonic probe.
The microcobjective is fixed on inside bowl-shape hollow focusing ultrasonic detector, and guarantee microcobjective with it is bowl-shape hollow Focus the confocal point of ultrasonic detector;The ultrasonic coupling cup for holding ultrasonic coupling liquid is located at right above sample, bowl-shape hollow poly- Burnt ultrasonic detector and photomultiplier tube are placed in the surface of ultrasonic coupling cup, and wherein photomultiplier tube surpasses in bowl-shape hollow focus The top of detector of sound;
The optoacoustic fluorescence excitation light source, signal amplifier, photomultiplier tube, three dimensional scanning platform, binary channels are adopted parallel Truck is successively electrically connected with the computer with acquisition control software and image reconstruction software and motor control software;
The amplification factor of the signal amplifier is 70dB, and bandwidth is 50KHz~500MHz;
The signal amplifier is preferably multi-stage cascade amplifier;
The microcobjective is flat-field objective, and amplification factor is 4 times, 10 times, 20 times, 40 times, 100 times, image quality Only related with amplification factor, the more high then quality of multiple is better.
The model of the binary channels parallel acquisition card can be PCI2400 (production of NI company), but other models, such as Grinding magnificent capture card can also use.
The three dimensional scanning platform is made of two-dimentional electric platforms and lifting platform;The two-dimentional electric platforms are by stepping Motor and mobile platform are constituted, and are rotated by motor and mobile platform is driven to be moved forward and backward, two-dimentional electric platforms are by two this electricity It is mobile that four direction all around may be implemented in moving platform composition;It is mainly controlled by lifting platform in vertical direction to reach different The effect of plane.
The acquisition control software and image reconstruction software are Labview software, and program is voluntarily write;
The motor control software is Labview software, and program is voluntarily write;Imaging software can be compiled with Matlab software Voluntarily write.
The principle of the present invention is: only based on the optoacoustic-fluorescence complementary principle i.e. process of calcium ion fluorescent stimulated radiation There are two approach: radiation transistion and nonradiative transition.Fluorescence imaging and photoacoustic imaging are exactly to the energy generated in the two approach It measures the detection of reformulations (fluorescence and optoacoustic) and realizes.What fluorescence imaging detected is the energy (fluorescence) of radiation transistion, and What photoacoustic imaging detected is the energy (photoacoustic signal) of nonradiative transition.For general calcium ion fluorescent, it is excited Radiation transistion and nonradiative transition process afterwards be all simultaneously occur and there is the mechanism of vying each other, actually occurring for the two is several Rate is then determined by the concentration of calcium ion.Usual calcium ion concentration is characterized by fluorescence signal intensity.Since optoacoustic, fluorescence are deposited In shifting complementary relationship, photoacoustic signal equally also can reflect the concentration variation of calcium ion.And photoacoustic signal is in group Transmission depth in knitting is firmly got than fluorescence up to arrives 1cm.Therefore, it may be implemented using optoacoustic-fluorescence complementary principle to deep layer The monitoring of calcium ion concentration.This method will be used for the research of Neuscience.
The present invention compared with the existing technology, have following advantages and effects
The calcium ion concentration monitoring of deep tissues may be implemented in method and apparatus of the invention;It is easy to operate, monitoring calcium from The sensitivity of sub- fluorescence probe can achieve 0.15 μM, can monitor the variation of deep tissues calcium ion concentration.The present invention can be real When detect deep tissues calcium ion concentration situation of change, it is possible thereby to be inferred to lesion tissue journey by the speed of the variation Degree.
Detailed description of the invention
Fig. 1 is the structural schematic diagram using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring device;Wherein, 1 For the computer with acquisition control software and image reconstruction software and motor control software;2 be three dimensional scanning platform;3 are Optoacoustic fluorescence signal excitaton source;4 be reflecting mirror;5 be the sample stage for placing sample;6 be ultrasonic coupling cup;7 be bowl-shape hollow poly- Burnt ultrasonic detector;8 be microcobjective;9 be spectroscope;10 be optical filter;11 be photomultiplier tube;12 be signal amplifier; 13 be extender lens group.
Fig. 2 is the relational graph of the optoacoustic of calcium ion concentration and calcium ion probe, fluorescence signal intensity.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited In this.
Embodiment 1
Structural schematic diagram using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring device is as shown in Figure 1.
It is the meter with acquisition control software and image reconstruction software and motor control software that the monitoring device, which includes: 1, Calculation machine;2 be three dimensional scanning platform;3 be optoacoustic fluorescence signal excitaton source;4 be reflecting mirror;5 be the sample stage for placing sample;6 are Ultrasonic coupling cup;7 be bowl-shape hollow focusing ultrasonic detector;8 be microcobjective;9 be spectroscope;10 be optical filter;11 be light Electric multiplier tube;12 be signal amplifier;13 be extender lens group.
Wherein, it optoacoustic fluorescence excitation light source 3, signal amplifier 12, photomultiplier tube 11, three dimensional scanning platform 2 and has The computer 1 of acquisition control software and image reconstruction software and motor control software is successively electrically connected;
The microcobjective 8 is fixed on inside bowl-shape hollow focusing ultrasonic detector 7, and guarantee microcobjective 8 with it is bowl-shape The confocal point of hollow focusing ultrasonic detector 7;The ultrasonic coupling cup 6 for holding ultrasonic coupling liquid is located at the sample stage for placing sample 5 surface, the two are an entirety, are fixed on three dimensional scanning platform 2, and three dimensional scanning platform 2 drives the sample for placing sample Sample platform 5 and ultrasonic coupling cup 6 are moved together and are scanned;Ultrasonic coupling liquid water is packed into ultrasonic coupling cup 6 to pass for photoacoustic signal It broadcasts;Bowl-shape hollow focusing ultrasonic detector 7 and photomultiplier tube 11 are placed in the surface of ultrasonic coupling cup 6, wherein photomultiplier transit Pipe 11 is in the bowl-shape hollow top for focusing ultrasonic detector 7;
The pulse laser that the optoacoustic fluorescent exciting source generator 3 issues is reflected by reflecting mirror 4, then passes through micro- object Mirror 8 is radiated on sample after focusing, i.e., the point hot spot that pulse laser is formed after over-focusing is fallen on sample, the optoacoustic letter of generation It number first passes through and to be received by bowl-shape hollow focusings ultrasonic detector 7 after ultrasonic coupling liquid, then by the amplification of signal amplifier 12; The fluorescence signal of generation is received after spectroscope 9 and optical filter 10 by photomultiplier tube 11, and fluorescence signal and photoacoustic signal are same When acquired by the computer 1 with acquisition control software and image reconstruction software and motor control software (Labview).
Three dimensional scanning platform 2 is mobile by the three-dimensional of the computer control sample with motor control software;It is every to have acquired one The photoacoustic signal of a point, 2 horizontal direction of three dimensional scanning platform, which is orderly moved, to move a step;After scanning through a plane, platform is indulged again It moves a step to shifting;To carry out point by point scanning to sample, for rebuilding 3-D image;It is final to obtain three-dimensional photoacoustce signal intensity point Cloth, to obtain calcium ion concentration distribution;After photoacoustic signal is collected, by maximum value projection algorithm (to pass through Matlab software Voluntarily write) the photoacoustce signal intensity distributed image that reconstructs sample, judge that the concentration of calcium ion becomes according to photoacoustce signal intensity Change;
Calcium ion fluorescent (present invention is by taking Rhod-2 as an example) is injected into the quasi- detection on the sample stage 5 for placing sample Region.Optoacoustic fluorescence signal excitaton source 3 exports pulse laser and is reflected by reflecting mirror 4, impinges perpendicularly in extender lens group 13. After expanding, the laser scattered is detected by photomultiplier tube 9 to calibrate the shake of laser energy light beam.Laser beam passes through aobvious Speck mirror 8 focuses on monitoring region.Calcium ion fluorescent is generated photoacoustic signal and fluorescence signal, optoacoustic letter after laser excitation It is then ultrasonic by bowl-shape hollow focusings of 8 lower section of microcobjective number by the super coupling liquid water coincidence of the inside of ultrasonic coupling cup 6 Detector 7 receives.Test sample is placed on three dimensional scanning platform 2, by the computer control sample equipped with motor control software Three-dimensional is mobile.Every photoacoustic signal for having acquired a point, 2 horizontal direction of three dimensional scanning platform, which is orderly moved, to move a step.When scanning through After one plane, platform vertically moves a step again.It is final to obtain three-dimensional photoacoustce signal intensity distribution, to reflect calcium ion concentration point Cloth.Photoacoustic signal passes through signal amplifier 12, the collected card acquisition of data, and is transferred to acquisition control software and image weight The computer 1 for building software and motor control software, handles data, be shown to reflection calcium ion concentration figure or Person's image.
Embodiment 2
Detection device described in Application Example 1 is realized to be monitored using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration.
(1) calcium ion fluorescent of same concentrations (by taking Rhod-2 as an example) is placed on molten equipped with different calcium ion concentrations In the ware of liquid, the fluorescence signal detected at this time enhances with the increase of calcium ion concentration.When covering one layer of 1mm thickness on ware After chicken-breasted (imitated biological tissue), fluoroscopic imaging systems can't detect fluorescence signal.
(2) the optoacoustic fluorescence signal excitaton source of Rhod-2 use semiconductor pumped laser, output wavelength 532nm, Pulsewidth is 10ns, and repetition rate is 100Hz~10KHz.The pulse laser that above-mentioned laser generates, focuses on by microcobjective On Rhod-2, photoacoustic signal and fluorescence signal are generated.Photoacoustic signal is by bowl-shape hollow focusing ultrasonic detector (dominant frequency 10MHz) It receives.Photoacoustic signal is transmitted after signal amplifier amplifies and is stored into computer.It is dense that calcium ion is analyzed by software The variation of degree.
(3) after handling the data of acquisition, the optoacoustic and fluorescence of sample are reconstructed by the algorithm of maximum value projection Then image passes through the available photoacoustce signal intensity value relevant with calcium ion concentration of peak-to-peak value for the number of winning the confidence, can obtain such as Fig. 2 photoacoustic signal and calcium ion concentration relational graph, and then can reflect the concentration variation of calcium ion.From figure 2 it can be seen that light Sound, fluorescence signal are shifting, and there is complementary relationships.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention, It should be equivalent substitute mode, be included within the scope of the present invention.

Claims (6)

1. a kind of with the monitoring method for utilizing optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring device, feature It is to include the following steps:
(1) using calcium ion fluorescent as optoacoustic calcium ion probe;
(2) calcium ion fluorescent is injected into the region of quasi- detection;
(3) after the pulse laser that optoacoustic fluorescence signal excitaton source issues crosses microcobjective, detection zone is focused on, so that calcium ion Fluorescence probe is generated photoacoustic signal and fluorescence signal after laser excitation;
(4) photoacoustic signal is received after passing through ultrasonic coupling liquid by bowl-shape hollow focusing ultrasonic detector, then amplifies by signal Device amplification;Fluorescence signal is received after spectroscope and optical filter filter by photomultiplier tube;Two paths of signals is parallel by binary channels Capture card acquires simultaneously, then data are transmitted and are stored into the computer with acquisition control software and image reconstruction software;
(5) it is placed in three-dimensional together with test sample and the ultrasonic coupling cup for holding ultrasonic coupling liquid to put down on platform, by being equipped with motor The three-dimensional for controlling the computer control sample of software is mobile;The photoacoustic signal of a point, three dimensional scanning platform level side are acquired It moves a step to orderly shifting;After scanning through a plane, platform vertically moves a step again;To carry out point by point scanning to sample, use In reconstruction 3-D image;
(6) after the photoacoustic signal of calcium ion fluorescent is collected, calcium ion probe light is reconstructed by maximum value projection algorithm Acoustic signal intensity distributed image judges that the concentration of calcium ion changes according to photoacoustce signal intensity;
(7) pass through the photoacoustce signal intensity of the calcium ion fluorescent of detection single-point, the change of the real-time monitoring calcium ion concentration Change;
The calcium ion fluorescent is Rhod-2;
The bowl-shape hollow dominant frequency for focusing ultrasonic detector is 10MHz, hollow focusing probe;
Maximum value projection algorithm described in step (6) is voluntarily write by Matlab software;
Detection single-point described in step (7) utilizes the pulse laser of high repetition frequency 10KHz and the capture card of high sampling rate 200M/s;Described includes that optoacoustic fluorescence signal swashs using optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring device It rises, bowl-shape hollow focusing ultrasonic detector, photomultiplier tube, reflecting mirror, spectroscope, extender lens group, microcobjective, ultrasound Couple cup, sample stage, three dimensional scanning platform, optical filter, signal amplifier, binary channels parallel acquisition card, with acquisition control it is soft The computer of part and image reconstruction software and motor control software;The microcobjective, which is fixed on bowl-shape hollow focusing ultrasound, to be visited It surveys inside device, and guarantees microcobjective and the bowl-shape hollow confocal point of focusing ultrasonic detector;It is described to hold the super of ultrasonic coupling liquid Acoustical coupling cup is located at right above sample, it is bowl-shape it is hollow focus ultrasonic detector and photomultiplier tube be placed in ultrasonic coupling cup just on Side, wherein photomultiplier tube is in the bowl-shape hollow top for focusing ultrasonic detector;
The optoacoustic fluorescence excitation light source, signal amplifier, photomultiplier tube, three dimensional scanning platform, binary channels parallel acquisition card It is successively electrically connected with the computer with acquisition control software and image reconstruction software and motor control software.
2. according to right ask 1 described in monitoring method, it is characterised in that: the optoacoustic fluorescence signal excitaton source be pulse laser Device, for output laser pulse width be nanosecond or picosecond laser, output wavelength 532nm, 675~1000nm, repeatedly Frequency 20Hz~10KHz.
3. monitoring method according to claim 1, it is characterised in that: the amplification factor of the signal amplifier is 70dB, bandwidth are 50KHz~500MHz.
4. monitoring method according to claim 1, it is characterised in that: the signal amplifier is multi-stage cascade amplification Device.
5. monitoring method according to claim 1, it is characterised in that: the three dimensional scanning platform is by two-dimentional electric platforms It is constituted with lifting platform;The two-dimentional electric platforms are made of stepper motor and mobile platform, are rotated by motor and are driven movement Platform is moved forward and backward, and two-dimentional electric platforms are made of two this electric platforms, realizes that all around four direction is mobile;Perpendicular Histogram is controlled to by lifting platform to achieve the effect that Different Plane.
6. monitoring method according to claim 1, it is characterised in that: the acquisition control software and image reconstruction software It is Labview software;
The motor control software is Labview software.
CN201510896712.0A 2015-12-07 2015-12-07 Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device Expired - Fee Related CN105548102B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510896712.0A CN105548102B (en) 2015-12-07 2015-12-07 Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510896712.0A CN105548102B (en) 2015-12-07 2015-12-07 Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device

Publications (2)

Publication Number Publication Date
CN105548102A CN105548102A (en) 2016-05-04
CN105548102B true CN105548102B (en) 2019-06-28

Family

ID=55827442

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510896712.0A Expired - Fee Related CN105548102B (en) 2015-12-07 2015-12-07 Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device

Country Status (1)

Country Link
CN (1) CN105548102B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113576415A (en) * 2021-08-04 2021-11-02 广东光声医疗科技有限公司 Four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system
CN117030621A (en) * 2023-09-11 2023-11-10 深圳大学 Marking-free laser histological imaging system and imaging method

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102621115A (en) * 2012-02-27 2012-08-01 华南师范大学 Confocal simultaneous opto-acoustic imaging and fluorescence imaging method and device
CN102928346A (en) * 2012-10-18 2013-02-13 中国科学院深圳先进技术研究院 Dual-module imaging system
CN103389273A (en) * 2013-08-01 2013-11-13 中国科学院自动化研究所 Photo-acoustic and optical integrated multi-mode imaging system
CN103393408A (en) * 2013-08-20 2013-11-20 中国科学院自动化研究所 Photoacoustic and fluorescent circulation mutual promotion imaging method

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140271475A1 (en) * 2013-03-12 2014-09-18 The Board Of Trustees Of The Leland Stanford Junior University Cellulose nanoparticle biodegradable photoacoustic contrast agents

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102621115A (en) * 2012-02-27 2012-08-01 华南师范大学 Confocal simultaneous opto-acoustic imaging and fluorescence imaging method and device
CN102928346A (en) * 2012-10-18 2013-02-13 中国科学院深圳先进技术研究院 Dual-module imaging system
CN103389273A (en) * 2013-08-01 2013-11-13 中国科学院自动化研究所 Photo-acoustic and optical integrated multi-mode imaging system
CN103393408A (en) * 2013-08-20 2013-11-20 中国科学院自动化研究所 Photoacoustic and fluorescent circulation mutual promotion imaging method

Also Published As

Publication number Publication date
CN105548102A (en) 2016-05-04

Similar Documents

Publication Publication Date Title
US8289502B2 (en) Measurement apparatus and measurement method
EP1303756B1 (en) Apparatus and method for probing light absorbing agents in biological tissues
CN104883965B (en) Subject information obtaining device, display methods, program and processing unit
CN100446730C (en) Photoacoustic imaging and chromatographic imaging method based on acoustic lens and apparatus thereof
CN102621115B (en) Confocal simultaneous opto-acoustic imaging and fluorescence imaging method and device
WO2007088709A1 (en) 3d acoustic imaging device and 3d acoustic imaging method
CN100366227C (en) Photoacoustic blood vessel imaging method and equipment for monitoring photodynamic tumor treating effect
CN106560160A (en) Object Information Acquiring Apparatus And Control Method Thereof
US9357928B2 (en) Vibrational photoacoustic tomography using Raman laser
JP2012135368A (en) Photoacoustic imaging apparatus
CN109363645A (en) A kind of human vas detection method based on Laser Photoacoustic Spectroscopy
CN109363644A (en) A kind of detection system for differentiating photoacoustic imaging based on coaxial time domain
CN101336832A (en) Pulse type optical acoustic scanning soft-tissue imaging method and device
CN105548102B (en) Utilize optoacoustic-fluorescence complementary principle deep layer calcium ion concentration monitoring method and device
Karagoz et al. Terahertz pulsed imaging study of dental caries
CN109497964A (en) A kind of human vas detection system based on Laser Photoacoustic Spectroscopy
US20160051149A1 (en) Photoacoustic Probe for Burn Injury Diagnosis
CN103018171B (en) Wide-frequency-band optical-acoustic and fluorescent double-imaging device without energy converter and detection method thereof
CN109856082A (en) The detection method and detection device of quick-fried pearl in cigaratte filter
CN105699295B (en) Utilize the quantitative detecting method and device of optoacoustic fluorescence signal ratio measurement pH value
JP2013195176A (en) Electromagnetic wave pulse measuring device, electromagnetic wave pulse measuring method, and application device using electromagnetic wave pulse measuring device
Pilatou et al. Analysis of three-dimensional photoacoustic imaging of a vascular tree in vitro
CN109363636A (en) A kind of detection method for differentiating photoacoustic imaging based on coaxial time domain
CN107647852B (en) System and method for imaging in organism tissue
Daoudi et al. Handheld probe for portable high frame photoacoustic/ultrasound imaging system

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20190628

Termination date: 20201207

CF01 Termination of patent right due to non-payment of annual fee