CN107684441A - A kind of Raman microprobe device with fine needle aspiration biopsy's function - Google Patents
A kind of Raman microprobe device with fine needle aspiration biopsy's function Download PDFInfo
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- CN107684441A CN107684441A CN201710903285.3A CN201710903285A CN107684441A CN 107684441 A CN107684441 A CN 107684441A CN 201710903285 A CN201710903285 A CN 201710903285A CN 107684441 A CN107684441 A CN 107684441A
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- raman microprobe
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- condenser lens
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- syringe
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- 238000001069 Raman spectroscopy Methods 0.000 title claims abstract description 78
- 238000001574 biopsy Methods 0.000 title claims abstract description 25
- 239000013307 optical fiber Substances 0.000 claims description 9
- 230000035945 sensitivity Effects 0.000 claims description 5
- 230000005540 biological transmission Effects 0.000 claims description 3
- 230000001360 synchronised effect Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 210000001519 tissue Anatomy 0.000 abstract description 18
- 239000000523 sample Substances 0.000 abstract description 13
- 210000003205 muscle Anatomy 0.000 abstract description 4
- 210000000278 spinal cord Anatomy 0.000 abstract description 3
- 241000287828 Gallus gallus Species 0.000 description 8
- 238000001237 Raman spectrum Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
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- 238000004458 analytical method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 241000272201 Columbiformes Species 0.000 description 2
- 238000003841 Raman measurement Methods 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
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- 238000011160 research Methods 0.000 description 2
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- 102000016397 Methyltransferase Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
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- 238000010586 diagram Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
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- 235000013372 meat Nutrition 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/02—Instruments for taking cell samples or for biopsy
- A61B10/0233—Pointed or sharp biopsy instruments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/02—Instruments for taking cell samples or for biopsy
- A61B10/0233—Pointed or sharp biopsy instruments
- A61B10/0283—Pointed or sharp biopsy instruments with vacuum aspiration, e.g. caused by retractable plunger or by connected syringe
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- 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
Abstract
The invention discloses a kind of Raman microprobe device with fine needle aspiration biopsy's function, including：Fixed mount, travelling carriage, syringe, light source, collimation lens, bandpass filter, dichroic mirror, first condenser lens, Raman microprobe, long-length filter, second condenser lens and spectrometer, first condenser lens and the second condenser lens are arranged on the both sides of dichroic mirror, the bandpass filter is arranged on the front of dichroic mirror, the Raman microprobe extends to the second condenser lens through syringe needle and syringe piston axle, the long-length filter is arranged on the inside of the first condenser lens, the collimation lens is arranged on the outside of bandpass filter.By the above-mentioned means, the Raman microprobe device of the present invention with fine needle aspiration biopsy's function, when the different depth for probe being placed in tissue, the type of this tissue（That is muscle, fat, spinal cord etc.）It can be identified in probe tip.
Description
Technical field
The present invention relates to medical instruments field, more particularly to a kind of Raman with fine needle aspiration biopsy's function
Probe unit.
Background technology
Fine needle aspiration biopsy（FNAB）It is that one kind places fine needle first, then extracts necessary cell, finally provides biological disease
The technology of Neo-Confucianism/cytodiagnosis.FNAB is a kind of safety economy, has minimum complication and the treatment received by many patients
Process.FNAB is used to diagnose the tumour for being easy to discover in itself, for example those are grown on head and neck, chest, belly, thoracic cavity/lung
And the tumour of prostate.However, when extract is not diagnosable, it is usually because material is inadequate, FNAB needs to repeat
Go or indicated to consider excision according to clinic.Particularly, negative diagnostic can not exclude the possibility of malignant tumour completely, if
There is the doubt of any malignant tumour, it is necessary that tumor tissue biopsy is carried out in a manner of a kind of opening, but if can obtain
This process of more preferable diagnostic message can avoid.In view of the limitation above with respect to FNAB, it is desirable to related scientific research personnel
New Advanced Mode can be developed to guide FNAB.Introscope ultrasonic wave（EUS）The FNA of guiding is once once in clinic
Upper use.However, EUS sensitivity is not high, it is probably derived from FNAB sampling error or EUS paracentesis depth limitation causes
Deeper region in some tissues（Region immediately ahead of tracheae）It can not be observed well.
Spectroscopy technology（Such as fluorescence, diffusing reflection and Raman）In pre-cancer and internal organ（Such as esophagus, stomach, colon, bladder
And lung etc.）Cancer diagnosis in carried out comprehensive research, and result shows that it has sensitivity more than 90% and more than 90%
Specificity.Particularly, Raman spectroscopy is a kind of uniquely inelastic optical scattering technology based on molecular vibration, and this technology can
For detecting biochemistry and biomolecular science structure and converting configuration for disease.
The content of the invention
The present invention solves the technical problem of provide a kind of Raman spy with fine needle aspiration biopsy's function
Needle device, solve the problems, such as that biological tissue suction, detection and different depth tissue detect in real time.
In order to solve the above technical problems, one aspect of the present invention is：There is provided a kind of with FNA work
The Raman microprobe device of tissue examination function, including：Fixed mount, travelling carriage, syringe, light source, collimation lens, bandpass filtering
Device, dichroic mirror, the first condenser lens, Raman microprobe, long-length filter, the second condenser lens and spectrometer, the cunning
Moving frame and syringe are co-axially located on fixed mount, are provided with guide rail corresponding with travelling carriage on the fixed mount, described two to
Color speculum is arranged on travelling carriage, and first condenser lens and the second condenser lens are arranged on the two of dichroic mirror
Side, the bandpass filter are arranged on the front of dichroic mirror, are provided with the syringe and point to the second condenser lens
Syringe piston axle, the syringe end is provided with syringe needle, and the Raman microprobe passes through syringe needle and note
Emitter piston shaft and extend to the second condenser lens, the long-length filter is arranged on the inside of the first condenser lens, the spectrum
It is provided with the first optical fiber between instrument and the first condenser lens to be connected, the collimation lens is arranged on the outside of bandpass filter, institute
State and the second optical fiber is provided between collimation lens and light source is connected.
In a preferred embodiment of the present invention, the Raman microprobe is any type optical fiber, the Raman microprobe it is straight
Footpath is several microns ~ hundreds of microns.
In a preferred embodiment of the present invention, the wavelength of the light source is 785nm.
In a preferred embodiment of the present invention, the light source is near-infrared laser.
In a preferred embodiment of the present invention, the Raman microprobe rear end is fixed on travelling carriage and focused on second saturating
Mirror keeps synchronous.
In a preferred embodiment of the present invention, the feature cutoff wavelength of the long-length filter is 800nm.
In a preferred embodiment of the present invention, it is provided with sheath outside the Raman microprobe.
In a preferred embodiment of the present invention, the spectrometer is near-infrared sensitivity Raman spectrometer.
In a preferred embodiment of the present invention, the reflected wavelength range of the dichroic mirror is 450nm-800nm,
Transmission peak wavelength scope is 800nm-1400nm.
In a preferred embodiment of the present invention, the Raman microprobe is with slip of the travelling carriage on guide rail and in syringe
Needle stretches.
The beneficial effects of the invention are as follows：A kind of Raman with fine needle aspiration biopsy's function that the present invention points out is visited
Needle device, creating one kind both has FNAB functions, can realize " difunctional " probe of single structure biopsy again, can insert
Enter tissue（As skin, brain, spinal cord, blood vessel, joint, tooth, bone, head, neck, chest, lymph node, belly, liver, thoracic cavity/lung,
Bladder, kidney, prostate etc.）Middle progress abnormality is identified and is biological pathology/cell under the positive instruction of Raman Measurement
Learn to assess and collect tissue and cell, while the single needle for providing Raman spectrum analysis detection and suspected lesion tissue punctures live body inspection
Look into, when the different depth for probe being placed in tissue, the type of this tissue（That is muscle, fat, spinal cord etc.）Can be in probe tip
It is identified, it is truly realized not by the raman spectroscopy measurement of effect of depth.
Brief description of the drawings
Technical scheme in order to illustrate the embodiments of the present invention more clearly, make required in being described below to embodiment
Accompanying drawing is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the present invention, for
For those of ordinary skill in the art, on the premise of not paying creative work, it can also be obtained according to these accompanying drawings other
Accompanying drawing, wherein：
Fig. 1 is a kind of structure of the preferred embodiment of Raman microprobe device one with fine needle aspiration biopsy's function of the present invention
Schematic diagram；
The Raman light for illustrating pigeon breast, heart and the chicken lung by being obtained during Raman microprobe progress 1.5mm punctures exemplary Fig. 2
Spectrogram；
The Raman spectrum detection figure for illustrating different depth undertissue exemplary Fig. 3.
Embodiment
The technical scheme in the embodiment of the present invention will be clearly and completely described below, it is clear that described implementation
Example is only the part of the embodiment of the present invention, rather than whole embodiments.It is common based on the embodiment in the present invention, this area
All other embodiment that technical staff is obtained under the premise of creative work is not made, belong to the model that the present invention protects
Enclose.
Fig. 1 ~ Fig. 3 is referred to, the embodiment of the present invention includes：
A kind of Raman microprobe device with fine needle aspiration biopsy's function, including：Fixed mount 20, travelling carriage 13, injection
Device 5, light source 12, collimation lens 10, bandpass filter 19, dichroic mirror 3, the first condenser lens 2, Raman microprobe 15, length
Ripple filter plate 18, the second condenser lens 4 and spectrometer 9, the travelling carriage 13 and syringe 5 are co-axially located on fixed mount 20,
Guide rail 17 corresponding with travelling carriage 13 is provided with the fixed mount 20, the dichroic mirror 3 is arranged on travelling carriage 13,
The condenser lens 4 of first condenser lens 2 and second is arranged on the both sides of dichroic mirror 3, is provided with the syringe 5
The syringe piston axle 6 of the second condenser lens 4 is pointed to, Raman microprobe 15 can be carried out along moving for guide rail 17 using travelling carriage 13
Dragging, synchronism is good.
The bandpass filter 19 is arranged on the front of dichroic mirror 3, and the end set of syringe 5 has syringe
Syringe needle 7, the Raman microprobe 15 extends to the second condenser lens 4 through syringe needle 7 and syringe piston axle 6, described
The rear end of Raman microprobe 15 is fixed on travelling carriage 13 and keeps synchronous with the second condenser lens 4.
The long-length filter 18 is arranged on the inner side of the first condenser lens 2, the condenser lens 2 of spectrometer 9 and first it
Between be provided with the first optical fiber 1 and be connected, the collimation lens 10 is arranged on the outside of bandpass filter 19, the collimation lens 10 with
The second optical fiber 11 is provided between light source 12 to be connected.The output of the light source 12 is oriented to bandpass filter by collimation lens 10
19, and the second condenser lens 4 is oriented to by dichroic mirror 3, second condenser lens 4 is beaten light by Raman microprobe 15
To sample 8, the reflected light of sample 8 is successively back through Raman microprobe 15, the second condenser lens 4 and dichroic mirror 3, immediately
And the first condenser lens 2 is entered by the long-length filter 18, most reflected light is sent into spectrometer 9 at last.
The Raman microprobe 15 is any type optical fiber, a diameter of several microns ~ hundreds of microns of the Raman microprobe 15, is fitted
Answering property is good.The wavelength of the light source 12 is 785nm, using near-infrared laser, the feature cutoff wavelength of the long-length filter 18
It is 800nm, the spectrometer 9 is near-infrared sensitivity Raman spectrometer.
Sheath 16 is provided with outside the Raman microprobe 15, strengthens the protection of Raman microprobe 15, the bottom of syringe piston axle 6
Piston 14 on drill and be that sheath 16 is oriented to, installation facility, supportive is good.Syringe piston axle 6 is using progress manually
Regulation, or slide rail and pushing meanss, the regulation of auxiliary syringe piston shaft 6 corresponding to increase on fixed mount 20.
The reflected wavelength range of the dichroic mirror 3 is 450nm-800nm, and transmission peak wavelength scope is 800nm-
1400nm。
The Raman microprobe 15 stretches with slip of the travelling carriage 13 on guide rail 17 in the end of syringe needle 7, convenient
Aspirated or detected in insertion test serum or sample 8, depth adjustment is flexible.
In vivo in real time in detection, this system can be in a large amount of organs（Including lung, esophagus, stomach, colon, uterine neck, oral cavity
And skin）In admirably tell benign and malignant tissue, present higher accuracy in detection, can provide and continuously examine in real time
Break, illustrate the ability that Raman spectroscopy realizes optical biopsy.
It can realize that real-time biological tissue is extracted and detected, pathology evaluation is carried out to cell and tissue.Specifically
It is exactly that, when incident light irradiation histocyte, histiocytic molecular vibration can cause incident light that non-resilient optical scattering occurs,
Cause the wavelength of reflected light that stokes shift and anti-Stokes skew occurs.
Assuming that incident light frequency is v, Raman frequency shift p, the then stokes light reflected is vstokes=v-p, it is anti-this
Lentor light is vanti-stokes=v+p.Stokes light light is stronger, and anti-Stokes light is weaker.Because Raman spectrum
Frequency shift (FS) is solely dependent upon the structure of scattering molecule, unrelated with input light frequency, therefore Raman spectrum can be used as molecular vibration
The Fingerprint of energy level, huge effect can be played in histocyte detection.
The technical scheme of the application can realize that biological tissue extracts and optical texture cell detection function simultaneously.Raman pin
Type probe can be used for primary clinical in live body detects in real time and study, ripe Raman needle-like probe Ying Yuxian in organizations
Some FNAB Clinical Processings processes are consistent as far as possible.
The operating process of Raman microprobe is as follows：
（1）Initial position：When syringe needle 7 enters suspicious region in the Conducted Puncture of ultrasonic wave, the end of Raman microprobe 15
Portion remains stationary as in the syringe needle 7 and at several millimeters of the end of syringe needle 7.
（2）Raman spectroscopy measurement：The elongation of Raman microprobe 15 is carried out at several millimeters of 7 end of syringe needle
Raman spectroscopy measurement.
（3）Raman microprobe is withdrawn：Raman microprobe 15 is retreated from syringe needle 7 to the bottom of syringe 5.
（4）Suction：Syringe piston axle 6 retreats with piston 14 so that keeps vacuum to be inhaled for cell in syringe 5
Enter.
（5）Go out pin：Syringe needle 7 is removed from the end of syringe 5.
（6）Take out：Syringe 5 is extruded to take out and be positioned on a microslide sample, for further
Histopathology/cytological analysis.
The drawing for illustrating pigeon breast, heart and the chicken lung by being obtained during Raman microprobe progress 1.5mm punctures exemplary Fig. 2
Graceful spectrogram.
Raman peaks in Raman spectrogram can be identified by biomolecular science, for example, at 2855/cm and 2885/cm
（Symmetrical and asymmetric methylene fat stretching vibration（symmetric and asymmetric CH2 stretching of
lipids））And at 2935/cm（Methyltransferase protein stretching vibration（CH3 stretching of proteins））.Shown in Fig. 2
As a result confirm that Raman microprobe has and realize optical biopsy and further to realize that histopathology/cytological analysis is entered
The dual-use function of capable FNA.
The Raman spectrum detection figure for illustrating different depth undertissue exemplary Fig. 3.
Test model is made up of upper and lower two layers of tissue, and upper strata is 2mm chicken muscle, and lower floor is 2mm chicken fat group
Knit.Fig. 3 a are when Raman needle-like Fine needle biopsy depth is respectively 1mm and 3mm Raman spectrum.Fig. 3 b are typical top layer chicken flesh
The typical Raman spectrum of meat tissue and bottom chicken adipose tissue.Obviously, when paracentesis depth is 1mm, the Raman signal that detects
The overwhelming majority shows as top layer musculature；Conversely, when paracentesis depth is 3mm, the Raman signal overwhelming majority table that detects
It is now bottom adipose tissue.For the Raman spectrum obtained from two layers of tissue model, we are with least-squares regression approach pair
Its further quantitative analysis, as a result show has 86% to be shown as top layer for the Raman signal obtained when all paracentesis depths are 1mm
（That is chicken muscle）, and all Raman signals to being obtained when paracentesis depth is 3mm, wherein thering is 91% to be shown as bottom（That is chicken
Adipose tissue）.Experimental result above confirms that Raman needle-like probe is realized in double-layered structure's model not by paracentesis depth
The Raman Measurement of influence.
In summary, a kind of Raman microprobe device with fine needle aspiration biopsy's function that the present invention points out, behaviour
Facilitate, the active somatic cell of different depth can be aspirated and detected, is truly realized not by the Raman light of effect of depth
Spectrometry.
Embodiments of the invention are the foregoing is only, are not intended to limit the scope of the invention, it is every to utilize this hair
The equivalent structure or equivalent flow conversion that bright description is made, or directly or indirectly it is used in other related technology necks
Domain, it is included within the scope of the present invention.
Claims (10)
- A kind of 1. Raman microprobe device with fine needle aspiration biopsy's function, it is characterised in that including：Fixed mount, cunning Moving frame, syringe, light source, collimation lens, bandpass filter, dichroic mirror, the first condenser lens, Raman microprobe, long wave Filter plate, the second condenser lens and spectrometer, the travelling carriage and syringe are co-axially located on fixed mount, on the fixed mount Guide rail corresponding with travelling carriage is provided with, the dichroic mirror is arranged on travelling carriage, first condenser lens and Two condenser lenses are arranged on the both sides of dichroic mirror, and the bandpass filter is arranged on the front of dichroic mirror, institute The syringe piston axle for being provided with syringe and pointing to the second condenser lens is stated, the syringe end is provided with syringe needle Head, the Raman microprobe extend to the second condenser lens through syringe needle and syringe piston axle, the long wave filtering Piece is arranged on the inside of the first condenser lens, and the first optical fiber is provided between the spectrometer and the first condenser lens and is connected, institute State collimation lens to be arranged on the outside of bandpass filter, the second optical fiber is provided between the collimation lens and light source and is connected.
- 2. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The Raman microprobe is any type optical fiber, a diameter of several microns ~ hundreds of microns of the Raman microprobe.
- 3. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The wavelength of the light source is 785nm.
- 4. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The light source is near-infrared laser.
- 5. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The Raman microprobe rear end is fixed on travelling carriage and synchronous with the holding of the second condenser lens.
- 6. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The feature cutoff wavelength of the long-length filter is 800nm.
- 7. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that Sheath is provided with outside the Raman microprobe.
- 8. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The spectrometer is near-infrared sensitivity Raman spectrometer.
- 9. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, it is characterised in that The reflected wavelength range of the dichroic mirror is 450nm-800nm, and transmission peak wavelength scope is 800nm-1400nm.
- 10. the Raman microprobe device according to claim 1 with fine needle aspiration biopsy's function, its feature exist Stretched in, the Raman microprobe with slip of the travelling carriage on guide rail in syringe needle cephalic par.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113899727A (en) * | 2021-09-18 | 2022-01-07 | 中山大学 | Device and method for detecting vertical change of concentration of target object in sediment pore water |
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