CN107684441A - A kind of Raman microprobe device with fine needle aspiration biopsy's function - Google Patents

Abstract

The invention discloses a Raman probe device with the function of fine-needle aspiration biopsy, comprising: a fixed frame, a sliding frame, a syringe, a light source, a collimating lens, a band-pass filter, a dichroic mirror, a second A focusing lens, a Raman probe, a long-wave filter, a second focusing lens and a spectrometer, the first focusing lens and the second focusing lens are arranged on both sides of the dichroic mirror, and the bandpass filter is arranged on In front of the dichroic mirror, the Raman probe passes through the syringe needle and the syringe piston shaft and extends to the second focusing lens, the long-wave filter is arranged inside the first focusing lens, and the collimating lens is arranged on the inside of the first focusing lens. outside the bandpass filter. Through the above method, the Raman probe device with the function of fine needle aspiration biopsy according to the present invention, when the probe is placed at different depths of the tissue, the type of the tissue (ie muscle, fat, spinal cord, etc.) Can be identified at the tip of the probe.

Description

A Raman probe device capable of fine-needle aspiration biopsy

technical field

The invention relates to the field of medical devices, in particular to a Raman probe device with the function of fine needle aspiration biopsy.

Background technique

Fine Needle Aspiration Biopsy (FNAB) is a technique in which a fine needle is first placed, the necessary cells are withdrawn, and finally a biopathological/cytological diagnosis is given. FNAB is a safe and economical procedure with minimal complications and accepted by most patients. FNAB itself is used to diagnose easily detectable tumors, such as those in the head and neck, chest, abdomen, chest/lung, and prostate. However, when the aspirate is nondiagnostic, usually because of insufficient material, FNAB needs to be repeated or resection considered as clinically indicated. In particular, a negative diagnosis does not completely exclude the possibility of malignancy. If there is any suspicion of malignancy, a biopsy of the mass in an open manner is necessary, but this procedure can be avoided if better diagnostic information can be obtained. . Considering the above limitations regarding FNAB, it is hoped that relevant researchers can develop new and advanced ways to guide FNAB. Endoscopic ultrasound (EUS)-guided fine-needle aspiration was once in clinical use. However, the sensitivity of EUS is not high, which may be due to the sampling error of FNAB or the limitation of the puncture depth of EUS, so that some deeper areas in the tissue (the area directly in front of the trachea) cannot be well observed.

Spectroscopy techniques such as fluorescence, diffuse reflectance, and Raman have been thoroughly studied in the diagnosis of precancerous and visceral cancers such as esophagus, stomach, colon, bladder, and lung, and have been shown to have greater than 90% sensitivity and specificity greater than 90%. In particular, Raman spectroscopy is the only inelastic light scattering technique based on molecular vibrations that can be used to probe biochemical and biomolecular structures and transform configurations for disease.

Contents of the invention

The technical problem mainly solved by the present invention is to provide a Raman probe device with the function of fine-needle aspiration biopsy, which solves the problems of biopsy aspiration, detection and real-time detection of tissues of different depths.

In order to solve the above-mentioned technical problems, a technical solution adopted by the present invention is to provide a Raman probe device with the function of fine needle aspiration biopsy, including: a fixed frame, a sliding frame, a syringe, a light source, a collimating lens, Band-pass filter, dichroic mirror, first focusing lens, Raman probe, long-wave filter, second focusing lens and spectrometer, the sliding frame and the injector are coaxially arranged on the fixed frame, and the fixed frame There are guide rails corresponding to the slide frame, the dichroic reflector is set on the slide frame, the first focusing lens and the second focus lens are set on both sides of the dichroic reflector, the bandpass filter The syringe is arranged in front of the dichroic mirror, the syringe piston axis pointing to the second focusing lens is arranged in the syringe, the syringe needle is arranged at the end of the syringe, and the Raman probe passes through the syringe needle and the syringe piston The axis extends to the second focusing lens, the long-wave filter is arranged inside the first focusing lens, the first optical fiber is arranged between the spectrometer and the first focusing lens to connect, and the collimating lens is arranged on the bandpass filter Outside the device, a second optical fiber is provided between the collimating lens and the light source to connect.

In a preferred embodiment of the present invention, the Raman probe is any type of optical fiber, and the diameter of the Raman probe is several micrometers to hundreds of micrometers.

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 a near-infrared laser.

In a preferred embodiment of the present invention, the rear end of the Raman probe is fixed on a sliding frame and kept in sync with the second focusing lens.

In a preferred embodiment of the present invention, the characteristic cut-off wavelength of the long-wave filter is 800 nm.

In a preferred embodiment of the present invention, the Raman probe is provided with a sheath outside.

In a preferred embodiment of the present invention, the spectrometer is a near infrared sensitive Raman spectrometer.

In a preferred embodiment of the present invention, the reflection wavelength range of the dichroic mirror is 450nm-800nm, and the transmission wavelength range is 800nm-1400nm.

In a preferred embodiment of the present invention, the Raman probe expands and contracts at the end of the syringe needle as the carriage slides on the guide rail.

The beneficial effect of the present invention is: a kind of Raman probe device that has the function of fine needle aspiration biopsy pointed out by the present invention, has created a kind of " double function that has FNAB function, can realize single structure biopsy again. "Probes that can be inserted into tissues (such as skin, brain, spinal cord, blood vessels, joints, teeth, bones, head, neck, chest, lymph nodes, abdomen, liver, chest cavity/lungs, bladder, kidneys, prostate, etc.) for abnormal lesions Identify and collect tissues and cells for biopathology/cytology evaluation as positively indicated by Raman measurements, while providing Raman spectroscopic detection and single needle biopsy of suspected diseased tissue when probes are placed in different regions of the tissue Depth, the type of tissue (i.e. muscle, fat, spinal cord, etc.) can be identified at the tip of the probe, truly realizing Raman spectroscopy measurements that are not affected by depth.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings that need to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative work, wherein:

Fig. 1 is the structural representation of a preferred embodiment of a Raman probe device with fine needle aspiration biopsy function of the present invention;

Figure 2 exemplarily shows the Raman spectra of chicken breast, chicken heart and chicken lung obtained when a Raman probe is punctured at 1.5 mm;

Fig. 3 exemplarily shows the Raman spectrum detection images of tissues at different depths.

detailed description

The following will clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

Please refer to Fig. 1 ~ Fig. 3, the embodiment of the present invention comprises:

A Raman probe device with the function of fine needle aspiration biopsy, comprising: a fixed frame 20, a sliding frame 13, a syringe 5, a light source 12, a collimating lens 10, a bandpass filter 19, and a dichroic mirror 3. The first focusing lens 2, the Raman probe 15, the long-wave filter 18, the second focusing lens 4 and the spectrometer 9, the sliding frame 13 and the syringe 5 are coaxially arranged on the fixed frame 20, and the fixed frame 20 A guide rail 17 corresponding to the sliding frame 13 is arranged on the top, the dichroic mirror 3 is arranged on the sliding frame 13, and the first focusing lens 2 and the second focusing lens 4 are arranged on two sides of the dichroic reflecting mirror 3 On the side, the syringe 5 is provided with a syringe piston shaft 6 pointing to the second focusing lens 4, and the Raman probe 15 can be dragged by the movement of the carriage 13 along the guide rail 17, and the synchronization is good.

The bandpass filter 19 is arranged in front of the dichroic mirror 3, the syringe needle 7 is arranged at the end of the syringe 5, and the Raman probe 15 extends through the syringe needle 7 and the syringe piston shaft 6 to The second focusing lens 4 , the rear end of the Raman probe 15 is fixed on the carriage 13 to keep in sync with the second focusing lens 4 .

The long-wave filter 18 is arranged inside the first focusing lens 2, the first optical fiber 1 is arranged between the spectrometer 9 and the first focusing lens 2 to connect, and the collimator lens 10 is arranged outside the bandpass filter 19 , A second optical fiber 11 is provided between the collimator lens 10 and the light source 12 to connect. The output of the light source 12 guides the bandpass filter 19 through the collimating lens 10, and guides the second focusing lens 4 through the dichroic mirror 3, and the second focusing lens 4 directs the light to the Sample 8, the reflected light of sample 8 reversely passes through the Raman probe 15, the second focusing lens 4 and the dichroic mirror 3 in turn, then enters the first focusing lens 2 through the long-wave filter 18, and finally reflects The light is sent to a spectrometer 9 .

The Raman probe 15 is any type of optical fiber, and the diameter of the Raman probe 15 is several micrometers to hundreds of micrometers, and has good adaptability. The wavelength of the light source 12 is 785nm, using a near-infrared laser, the characteristic cut-off wavelength of the long-wave filter 18 is 800nm, and the spectrometer 9 is a near-infrared sensitive Raman spectrometer.

The Raman probe 15 is provided with a sheath 16 outside to strengthen the protection of the Raman probe 15. The piston 14 at the bottom of the syringe piston shaft 6 guides the sheath 16 by drilling a hole, which is convenient for installation and has good support. The syringe piston shaft 6 is adjusted manually, or a corresponding slide rail and a pushing device are added on the fixed frame 20 to assist the adjustment of the syringe piston shaft 6 .

The reflection wavelength range of the dichroic mirror 3 is 450nm-800nm, and the transmission wavelength range is 800nm-1400nm.

The Raman probe 15 expands and contracts at the end of the syringe needle 7 as the carriage 13 slides on the guide rail 17, so that it can be easily inserted into the tissue to be tested or the sample 8 for suction or detection, and the depth can be adjusted flexibly.

In real-time detection in vivo, this system can excellently distinguish benign and malignant tissues in a large number of organs, including lung, esophagus, stomach, colon, cervix, oral cavity, and skin, demonstrating high detection accuracy, reliable Provides continuous real-time diagnostics, demonstrating the ability of Raman spectroscopy to enable optical biopsy.

Real-time living tissue extraction and detection can be realized, and pathological evaluation of cells and tissues can be performed. Specifically, when the incident light irradiates the tissue cells, the molecular vibration of the tissue cells will cause inelastic optical scattering of the incident light, resulting in Stokes shift and anti-Stokes shift of the reflected light wavelength.

Assuming that the incident light frequency is v, and the Raman frequency shift is p, the reflected Stokes light is v _stokes =vp, and the anti-Stokes light is v _anti-stokes =v+p. Stokes light is stronger and anti-Stokes light is weaker. Because the frequency shift of the Raman spectrum only depends on the structure of the scattering molecules and has nothing to do with the frequency of the input light, the Raman spectrum can be used as a fingerprint spectrum of the molecular vibrational energy level, which can play a huge role in the detection of tissue cells.

The technical scheme of the present application can simultaneously realize the functions of living tissue extraction and optical tissue cell detection. Raman needle probes can be used in primary clinical research in live real-time detection, and mature Raman needle probes should be consistent with the existing FNAB clinical treatment process in tissue applications.

The operation process of the Raman probe is as follows:

(1) Initial position: when the syringe needle 7 punctures into the suspected area under the guidance of ultrasound, the end of the Raman probe 15 is inside the syringe needle 7 and a few millimeters away from the end of the syringe needle 7 and remains motionless.

(2) Raman spectrum measurement: the Raman probe 15 is extended to a few millimeters beyond the end of the syringe needle 7 to perform Raman spectrum measurement.

(3) Retraction of the Raman probe: the Raman probe 15 retreats from the syringe needle 7 to the bottom of the syringe 5 .

(4) Inhalation: The syringe piston shaft 6 drives the piston 14 to retreat, so that the vacuum in the syringe 5 is maintained for cell inhalation.

(5) Needle ejection: remove the syringe needle 7 from the end of the syringe 5 .

(6) Retrieval: Squeeze the syringe 5 to remove the sample and place it on a microscope slide for further histopathological/cytological analysis.

Figure 2 exemplarily shows the Raman spectra of chicken breast, chicken heart and chicken lung obtained when the Raman probe is punctured at 1.5mm.

Raman peaks in the Raman spectrum can be identified biomolecularly, for example, at 2855/cm and 2885/cm (symmetric and asymmetric CH2 stretching of lipids) and 2935/cm cm (CH3 stretching of proteins). The results shown in Figure 2 demonstrate the dual functionality of the Raman probe for optical biopsy and fine-needle aspiration for further histopathological/cytological analysis.

Fig. 3 exemplarily shows the Raman spectrum detection images of tissues at different depths.

The test model consists of upper and lower layers of tissue, the upper layer is 2mm chicken muscle tissue, and the lower layer is 2mm chicken adipose tissue. Figure 3a is the Raman spectra when the penetration depth of the Raman needle probe is 1mm and 3mm respectively. Figure 3b is a typical Raman spectrum of typical top chicken muscle tissue and bottom chicken fat tissue. Obviously, when the puncture depth is 1 mm, most of the detected Raman signals appear as the top muscle tissue; on the contrary, when the puncture depth is 3 mm, most of the detected Raman signals appear as the underlying fat tissue. For the Raman spectra obtained from the two-layer tissue model, we used the least squares regression method to further quantify it, and the results showed that 86% of the Raman signals obtained when the puncture depth was 1 mm were displayed in the top layer (that is, chicken muscle Tissue), while 91% of all Raman signals obtained at a puncture depth of 3 mm were shown as the underlying layer (ie, chicken adipose tissue). The above experimental results confirm that the Raman needle probe can achieve Raman measurement not affected by the puncture depth in the double-layer tissue model.

In summary, the Raman probe device with the function of fine needle aspiration biopsy pointed out by the present invention is easy to operate, can aspirate and detect living cells at different depths, and truly realizes that it is not affected by depth. Raman spectroscopy measurements.

The above descriptions are only examples of the present invention, and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process conversion made by using the content of the description of the present invention, or directly or indirectly used in other related technical fields, shall be The same reasoning is included in the patent protection scope of the present invention.

Claims (10)

1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.