CN104007089B - Scattered opto-acoustic detection method and opto-acoustic detector - Google Patents

Abstract

The invention discloses a scattered opto-acoustic detector. The scattered opto-acoustic detector comprises a light source, a sample chamber and an acoustic sensor. The inner wall of the peripheral side wall of the sample chamber is coated with a light absorption material layer; the light source is arranged outside one side of the bottom surface of the sample chamber and is used for irradiating the sample chamber; the acoustic sensor is communicated with the side wall of the sample chamber. The scattered opto-acoustic detector provided by the invention can be used for detecting scattered opto-acoustic signals of weak-absorption high-scattering samples, overcomes the defect that a transmitting opto-acoustic technique only aims at high-absorption samples, has the characteristics of simple and compact structure, small size, high sensitivity, convenience in use and the like, can be widely applied to the fields of clinical medical treatment and diagnosis and the like, and provides a novel representation means.

Description

A kind of scattering optoacoustic detection method and optoacoustic detector

Technical field

The present invention relates to a kind of optoacoustic detection technology, particularly to a kind of optoacoustic detection method of the sample for weak absorbing And its optoacoustic detector.

Background technology

With the development of modern science and technology, medical imaging has great significance to the Clinics and Practices of various diseases. It is the important means of the biological lesion tissue of research that biological tissue is carried out being imaged.At present, it is widely used imaging medically Method mainly has: x-ray imaging, nuclear magnetic resonance (magnetic reso nance tomography, mrt), ultra sonic imaging Deng.In these above-mentioned imaging techniques, all because radiation youngster causes certain damage to human body.X-ray also known as roentgen radiation, it There is the ability of penetrating material, but different to its penetrating power of different material, there is perniciasm.X-ray imaging is root According to the density of tissue and the difference of thickness, enable tissue that image to be formed on fluorescent screen or film, therefore some tissue diseases Change cannot judge, and long term frequent be would detract from health of people using x-ray imaging.Mrt technology is using in tissue Hydrogen nuclei is activated in magnetic field and occurs nmr phenomena to produce a kind of imaging technique of magnetic phenomenon.It has radiation And the features such as apparatus expensive.Ultra sonic imaging is a kind of Non-Destructive Testing to biological tissue, but it imaging method rely on The acoustic impedance of biological tissue, due to the no obvious difference of the acoustic reactance of some tumor tissues, this just limits the fortune of ultrasonic imaging technique With scope and but the contrast of its reconstructed picture is relatively low.

Photoacoustic imaging technology is a kind of Non-Destructive Testing medical imaging technology developing in recent years, it combine optical imagery and The advantage of ultra sonic imaging, is progressively becoming a new research direction of medical science Non-Destructive Testing.Optoacoustic effect is medical science optoacoustic The basis of imaging research.During with the light beam irradiation absorption body of time-varying, absorber produces ultrasound wave because of expanded by heating, this phenomenon Referred to as optoacoustic effect, the ultrasound wave of generation is referred to as photoacoustic signal.Medically, with section pulse laser uniform irradiation in biological tissue Surface, biological tissue absorb luminous energy be converted into heat energy, and make tissue local heat up, occur thermal-elastic expansion, produce ultrasonic letter Number, carry out image reorganization using suitable algorithm, just can get the photoacoustic image of biological tissue.Because photoacoustic imaging is to utilize Luminous energy absorb distribution come response organization within structure, be a kind of unionized, radiationless Non-Destructive Testing.It is tied effectively The advantage having closed the high-penetration depth of the high-resolution, high-contrast and pure acoustics imaging of pure optical imagery, achievable micron amount The imaging precision of level and the investigation depth of centimetres, have complete Noninvasive, no ionizing radiation, the prominent characteristic such as lossless, Biomedicine has and is widely applied very much prospect, such as: the detection of melanoma, microvessel structure and functional imaging, interior peep The medical imaging detection fields such as mirror technology, visualization gene expression imaging, molecular imaging, brain function imaging.

Please refer to Fig. 1 and Fig. 2, wherein, Fig. 1 is the structural representation of traditional optoacoustic spectroscopy detection system, and Fig. 2 is Operating diagram during target sample optoacoustic detection.Light source produces short-pulse laser s1, is expanded by optical element, forms intensity Target sample to be detected is exposed to, this target sample quickly absorbs beam energy, target as absorbing sample after modulation light beam Tissue expanded by heating in sample, produces sound wave s2, and this sound wave s2 outwards will propagate through tissue, can be placed on around sample Microphone s3 detect, photoacoustic signal is converted to the signal of telecommunication by microphone, this signal of telecommunication again pass through signal processing system shape Become image.Rotary scanning mode can be adopted, or using complex array detector it is possible to obtain irradiating in undertissue not in laser Photoacoustic waves intensity of pressure distribution with region.The size of optoacoustic wave pressure direct phase of degree of absorption to laser energy with tissue Close, light absorbs are stronger, then the photoacoustce signal intensity at this is higher.Therefore, using the photoacoustic waves distribution receipt detecting, by filter Ripple back projection carries out image reconstruction it is possible to obtain the light absorbs distributed image of tissue.

But, traditional opto-acoustic microscopic imaging technology is all produced for target sample itself or label absorption at present The detection of photoacoustic signal.However, in microbiological cell sample, not all samples are all to a certain specific wavelength pulse laser There is heat absorption, have many biological cell sample itself pulse laser cannot be absorbed and produce photoacoustic waves, thus light cannot be passed through Acoustic imaging technology detects the image of this type of sample.

Content of the invention

It is an object of the invention to overcoming the deficiencies in the prior art, providing and a kind of light weak absorbing sample can be detected Optoacoustic detector, realizes to unmarked weak absorbing biological cell sample opto-acoustic microscopic imaging.

In order to achieve the above object, the present invention employs the following technical solutions: a kind of optoacoustic detector, including light source, sample Room and sonic transducer；The inwall of four the week side of boss walls of this sample room is coated with light-absorbing material layer；Light source is arranged on sample room bottom surface one The external irradiation sample room of side, this sonic transducer is connected with the side wall of sample room.

Further, also include the coupled cavity that a pair of sound wave is amplified, the side wall of the input of this coupled cavity and sample room Connection, outfan is connected with sonic transducer.

Further, also include leading sound passage, the side wall of this one end and sample room of leading sound passage connects, the other end and coupling Close the input connection in chamber.

Further, described light-absorbing material layer is black oxidation iron layer.

Further, described sonic transducer is piezoelectric type sonic transducer, including piezoelectric membrane and peripheral circuit, this piezoelectric membrane So that acoustic signals are converted to voltage signal, the input of this peripheral circuit connects this pressure to the outfan being arranged on coupled cavity respectively The two poles of the earth of conductive film, and the voltage signal that it produces is amplified and filters.This piezoelectric membrane is pvdf thin film.

Further, this peripheral circuit includes sequentially concatenating charge amplifier, band filter, voltage amplifier and low Bandpass filter.

Compared to prior art, the scattering optoacoustic letter of the optoacoustic detector detectable weak absorbing strong scattering sample of the present invention Number, compensate for transmitting optoacoustic detection technology just for the strong defect absorbing sample；Meanwhile, achievable micro- with general laser scanning Mirror slitless connection, the scattering photoacoustic signal of detectable sample arbitrfary point, rebuild the scattering optoacoustic micro-image of sample, there is structure The features such as simply compact, small volume, sensitivity are high and easy to use, can be widely applied to the fields such as clinical treatment diagnosis, provides A kind of new characterization method.

Meanwhile, the present invention also provides a kind of scattering optoacoustic detection method.Its technical scheme is: a kind of scattering optoacoustic detection side Method, makes the target sample that laser irradiates weak absorbing produce scattered light, makes scattered light expose to light absorbent, this light absorbent absorbs Photon simultaneously produces corresponding sound wave, then obtains the image of target sample by detecting this sound wave.

Further, this light absorbent is the ferrum oxide of black.

The scattering photoacoustic signal of the scattering optoacoustic detection method detectable weak absorbing strong scattering sample of the present invention, compensate for passing Pass optoacoustic detection technology just for the strong defect absorbing sample.

Brief description

Fig. 1 is the structural representation of traditional optoacoustic spectroscopy detection system.

Fig. 2 is operating diagram during target sample optoacoustic detection.

Fig. 3 is a kind of structural representation of scattering optoacoustic detector of the present invention.

Fig. 4 is the circuit diagram of the peripheral circuit in Fig. 2.

Fig. 5 is the traditional optoacoustic microgram using prior art to a sample (oral cavity upper table chrotoplast).

Fig. 6 is the scattering optoacoustic microgram to same sample for a kind of scattering optoacoustic detector using the present invention.

Referring to drawings and the specific embodiments, the invention will be further described.

Specific embodiment

Because the weak absorbing biological cell sample as target sample cannot have enough heat absorption intensity to pulse laser, Thus the sound wave of sufficient intensity cannot be produced.In order that pulse laser can produce sound wave after target sample, inventor exists Increase in light path and there is the light absorbent of high absorption coefficient to produce sound wave.Obtain after light path order repeatedly adjusts, The light absorbent of light source, target sample and high absorption coefficient is sequentially placed on light path, the pulse laser being produced by light source is passing through After target sample, original optical path scatters, then via the material of high absorption coefficient after, create detectable sound wave, and this sound wave Carry the structural information of this target sample.Thus, there is provided a kind of scattering optoacoustic detector of detectable weak absorption sample.

Refer to Fig. 3, it is the structural representation of the optoacoustic detector of the present invention.This optoacoustic detector include light source 12, Sample room 14, lead sound passage 16, coupled cavity 18 and sonic transducer 19, the inwall of this sample room 14 is coated with a high absorption coefficient Light-absorbing material layer 15.Target sample a to be detected is arranged on coverslip 13, and is placed at the bottom centre of sample room 14 On window, light source detects to it after irradiating target sample a.This sample room 14, lead sound passage 16 and sequentially connect with coupled cavity 18, should Sonic transducer 19 is connected to one end of this coupled cavity 18, and is connected with signal processing apparatus or image processing apparatus (not shown). This sample room 14, lead sound passage 16, coupled cavity 18 and sonic transducer 19 and be arranged in a matrix case and be integrated into an entirety.

Specifically, this light source 12 is the pulsed light beam producing after continuous light source (400-2500nm) is subject to chopper modulation, its Form focus on light beam through microcobjective (not shown).

This sample room 14 is the chamber of closing, and it is symmetrical structure.In the present embodiment, this sample room 14 is cylinder, The inwall of its side coats the light-absorbing material layer 15 of high absorption coefficient, produces sound wave in order to absorb photon.And in this sample room Upper bottom surface is not coated by light-absorbing material layer, to avoid for the not trajectory light absorbs through sample being converted to sound wave.This light absorbent The material of layer can be: ferrum oxide, white carbon black, pine soot are idle, graphite, nigrosine, sulfuration nigrosine etc..In the present embodiment, this suction Optical material layer 15 is the iron oxide layer of black, and its thickness is between 0.05mm-0.3mm.

This leads sound passage 16 is superfine strip channel, and it connects the side wall of this sample cavity 14 and coupled cavity 18, using non- The material of sound absorption is made, and makes the sound wave edge producing in sample cavity 14 lead sound passage 16 and conducts to coupled cavity 18.In the present embodiment, This leads sound passage 16 is cylindrical channel, and its aperture is between 0.2mm-0.5mm.It should be noted that, this is led sound passage and is only biography Lead the passage of sound, be not the necessary structure of the present invention.

This coupled cavity 18 is similarly the chamber of closing, and the material using non-sound absorption is made, in the present embodiment, this coupled cavity For cylindrical structural.The volume of this coupled cavity 18 is matched with the volume leading sound passage 16, according to last of the twelve Earthly Branches nurse hertz resonance principle, sound Ripple produces resonance through multiple reflections in this coupled cavity 18, makes the amplitude of sound wave reach maximum, thus sonic transducer 19 can be made more Plus easily sense this acoustic signals.

This sonic transducer 19 includes piezoelectric membrane 192 and peripheral circuit 194.This piezoelectric membrane 192 is in the present embodiment Highly sensitive pvdf (polyvinylidene fluoride) piezoelectric membrane, in order to sense sound wave.In the present embodiment, this piezoelectric membrane 192 It is vertically arranged with the direction of vibration of sound wave, can farthest sense sound wave.In the present embodiment, this peripheral circuit 194 includes Charge amplifier 1942, band filter 1944, voltage amplifier 1946 and low pass filter 1948.This peripheral circuit has Input i1, i2 and outfan o1, o2.Wherein, input i1, i2 connects the two poles of the earth of piezoelectric membrane, outfan 01,02 respectively With the image processing apparatus (not shown) outside connection.The sound wave that coupled cavity 18 amplifies makes this piezoelectric membrane 192 produce respective tones The vibration of rate, due to there is positive piezoelectric effect, this piezoelectric membrane 192 converts mechanical energy into the signal of telecommunication, just produces and sound wave Frequency identical voltage.Then filtered by peripheral circuit 194 and by voltage amplification, show figure finally by image processing apparatus Picture.

Specifically, refer to Fig. 4, this charge amplifier 1942 includes operational amplifier a1, resistance r1, resistance r2, resistance R3, electric capacity c1 and electric capacity c2.The normal phase input end of described operational amplifier a1 passes through the input of resistance r1 and peripheral circuit I1 concatenates；The inverting input of described operational amplifier is electrically connected with the input i2 of this peripheral circuit；The two of described resistance r2 End is electrically connected with reverse input end with the normal phase input end of operational amplifier a1 respectively；Described electric capacity c1 is in parallel with this resistance r2； The two ends of described resistance r3 are electrically connected with outfan with the normal phase input end of operational amplifier a1 respectively；Described electric capacity c2 and this electricity Resistance 43 is in parallel.The outfan of operational amplifier a1 is as the outfan of charge amplifier.Charge amplifier is a kind of output voltage The preamplifier being directly proportional to input charge amount, makees the high-gain amplifier of the profound and negative feedbck of feedback element using electric capacity.Pressure Electric-type sensor internal impedance itself is very high, and the output signal of telecommunication is very faint, generally first sensor signal is first input into high input resistance In anti-preamplifier, after impedance exchanges, instruction can be input a signal into again with general amplification demodulatoring circuit In instrument or recorder.

This band filter 1944 includes operational amplifier a2, resistance r4, resistance r5, resistance r6, electric capacity c3 and electric capacity c4.The outfan of described operational amplifier a1 passes sequentially through the normal phase input end string of resistance r4, electric capacity c4 and operational amplifier a2 Connect；The negative-phase input of described operational amplifier a2 is electrically connected with the input i2 of peripheral circuit；Described resistance r5 two ends are respectively The input i2 of be electrically connected contact and peripheral circuit between resistance r4 and electric capacity c4 electrically connects；The two ends of described resistance r6 are divided Do not electrically connect with the normal phase input end of operational amplifier a2 and outfan；The two ends of described electric capacity c4 respectively with resistance r4 with electricity Hold the outfan electrical connection of be electrically connected contact and the operational amplifier a2 between c4.The outfan of operational amplifier a2 is as band logical The outfan of wave filter.This band filter is used for the signal of the Mid Frequency in filtered electrical signal.

This voltage amplifier 1946 includes operational amplifier a3, resistance r7, resistance r8 and resistance r9；Operational amplifier a2's Outfan is concatenated with the normal phase input end of operational amplifier a3 by resistance r7；The two ends of resistance r8 respectively with operational amplifier a3 Negative-phase input and peripheral circuit negative-phase input electrical connection；The two ends of described resistance r9 respectively with operational amplifier a3 Normal phase input end and outfan electrical connection.The outfan of described operational amplifier a3 is as the outfan of the anti-big device of voltage.

This low pass filter 1948 include operational amplifier a4, resistance r10, resistance r11, resistance r12, resistance r13 and Electric capacity c5.The outfan of operational amplifier a3 passes sequentially through the positive input of resistance r10 and resistance r12 and operational amplifier a4 End concatenation；The input of the two ends of resistance r11 be electrically connected contact and the peripheral circuit and resistance r10 and resistance r12 between respectively I2 electrically connects；The two ends of resistance r13 are electric with the negative-phase input of operational amplifier a4 and the input i2 of peripheral circuit respectively Connect；The two ends of resistance r14 are electrically connected with the normal phase input end of operational amplifier a4 and outfan respectively；Electric capacity c5 and resistance R14 is in parallel.The outfan of operational amplifier a4, as the outfan of low pass filter, is also the outfan of peripheral circuit simultaneously o1.This low pass filter is used for the low frequency signal in filtered electrical signal.

The optoacoustic detector of the present invention all can detect, its operation principle is as follows to the target sample of strong and weak light absorbs:

What light source produced washes bundle off through microcobjective formation focus on light beam, then passes through coverslip and is focused at target sample In the certain point of a.

When the sample that target sample a is strong light absorption, light beam is absorbed by target sample a, and target sample a is as absorption sample Product quickly absorb beam energy, the tissue expanded by heating in target sample a, produce sound wave.Due to the suction on the inwall of sample room 14 Optical material layer 15 only absorbs to light, and the sound wave that therefore target sample a produces will not be subject to this extinction material in sample room 14 The impact of the bed of material 15.The sound wave that sample a produces is exaggerated after leading sound passage 16 in coupled cavity 18, is then sensed by sound Device 19 is converted to the signal of telecommunication.

When target sample a is weak absorption or when not absorbing light, it is scattered when light beam is by target sample a, thus light Bundle changes the direction of conduct.The scattered light of different angles carries the structural information of the correspondence position of this target sample a.Light beam After being scattered during by target sample a, beat on the light-absorbing material layer 15 of the side wall coating of sample room 14, light-absorbing material layer 15 is inhaled It is converted into corresponding sound wave after receiving photon；And light beam is directed to the upper bottom surface of sample room 14 by the part of target sample a, by In the uncoated light absorbent in bottom surface of sample room 14, therefore, light beam is not translate across by the trajectory light part of target sample a Become sound wave.After sample a scattering, it is exaggerated in coupled cavity 18 through leading sound passage 16 through the sound wave that light absorbent produces, then The signal of telecommunication is converted to by sonic transducer 19.

Acoustic signals are converted to the signal of telecommunication by sonic transducer 19, and through charge amplifier, band filter, voltage amplification The voltage amplification of device and low pass filter and filter action, can carry out slitless connection with general laser scanning microscope, can visit The scattering photoacoustic signal of test sample product arbitrfary point, rebuilds the scattering optoacoustic micro-image of sample.

Refer to as Fig. 5 and Fig. 6.Wherein, Fig. 5 is the tradition using prior art to a sample (oral cavity upper table chrotoplast) Optoacoustic microgram, Fig. 6 is the scattering optoacoustic microgram to same sample for the optoacoustic detector using the present invention.Relatively two figures can Know, the scattering optoacoustic microgram in Fig. 6 is apparent, has higher resolution and contrast, and the resolution of imaging can reach about 0.3μm.

Compared to prior art, the scattering photoacoustic signal of the present invention detectable weak absorbing strong scattering sample, compensate for transmitting Optoacoustic detection technology is just for the strong defect absorbing sample；Meanwhile, can achieve and general laser scanning microscope slitless connection, can Detect the scattering photoacoustic signal of sample arbitrfary point, rebuild the scattering optoacoustic micro-image of sample, there is simple and compact for structure, volume The features such as little, sensitivity is high and easy to use, can be widely applied to the fields such as clinical treatment diagnosis, provides a kind of new sign handss Section.

The above is only the preferred embodiment of the present invention it is noted that above-mentioned preferred implementation be not construed as right The restriction of the present invention, protection scope of the present invention should be defined by claim limited range.For the art For those of ordinary skill, without departing from the spirit and scope of the present invention, some improvements and modifications can also be made, these change Enter and retouch also to should be regarded as protection scope of the present invention.

Claims (9)

1. a kind of scattering optoacoustic detector it is characterised in that: include light source, sample room and sonic transducer；The surrounding of this sample room The inwall of side wall is coated with light-absorbing material layer, and on sample room, the inwall of bottom surface is not coated by light-absorbing material layer；Light source is arranged on The external irradiation sample room of sample room bottom surface side；Described sonic transducer is piezoelectric type sonic transducer, including piezoelectric membrane with outward Enclose circuit, this sonic transducer is connected with the side wall of sample room.

2. optoacoustic detector according to claim 1 it is characterised in that: also include the coupling that sound wave is amplified a pair of Chamber, the input of this coupled cavity is connected with the side wall of sample room, and outfan is connected with sonic transducer.

3. optoacoustic detector according to claim 2 it is characterised in that: also include leading sound passage, this leads sound passage One end is connected with the side wall of sample room, and the other end is connected with the input of coupled cavity.

4. optoacoustic detector according to claim 3 it is characterised in that: described light-absorbing material layer be black oxidation iron layer.

5. optoacoustic detector according to claim 4 it is characterised in that: described sonic transducer be piezoelectric type sonic transducer, Including piezoelectric membrane and peripheral circuit, this piezoelectric membrane is arranged on the outfan of coupled cavity so that acoustic signals are converted to voltage letter Number, the input of this peripheral circuit connects the two poles of the earth of this piezoelectric membrane respectively, and the voltage signal that it is produced be amplified and Filtering.

6. optoacoustic detector according to claim 5 it is characterised in that: this piezoelectric membrane be pvdf thin film.

7. optoacoustic detector according to claim 6 it is characterised in that: the electric charge that this peripheral circuit includes sequentially concatenating is put Big device, band filter, voltage amplifier and low pass filter.

8. a kind of based on described in claim 1 scattering optoacoustic detector scattering optoacoustic detection method it is characterised in that: make to swash The target sample of light irradiation weak absorbing produces scattered light, makes to carry the scattering of the structural information of this weak absorbing sample correspondence position Illumination is incident upon the light-absorbing material layer of sample room four the week side of boss wall, and this light-absorbing material layer absorbs photon and produces corresponding sound wave, then leads to Cross sonic transducer and detect that this sound wave obtains the image of target sample.

9. according to claim 8 scattering optoacoustic detection method it is characterised in that: this light-absorbing material layer be black oxidation Ferrum.