KR101018635B1 - Ultrafast Laser Apparatus for Selective Ablation of Ocular Biosubstance - Google Patents

Abstract

Apparatus according to the present invention is a device for removing the biological material constituting the eyeball using a laser, the laser light source for generating a laser beam; An optical system that focuses the laser beam and irradiates the biological material; A stage for controlling the position of the biomaterial; And a laser controller configured to adjust fluence of the laser beam generated from the laser light source, wherein the laser controller adjusts the fluence of the laser beam according to Equation 1 below. It is characterized by controlling the removal depth of the.

(Equation 1)

If F _th (l _o ) ≤ F <F _th (l _t ): L = l _o ln (F / F _th (l _o ))

If F _th (l _t ) ≤ F: L = l _t ln (F / F _th (l _t ))

Where L is the removal depth in μm, F is the fluence of the laser beam in J / cm ² , l _o is 8.2 ± 2.2 μm, and F _th (l _o ) is 2.2 ± 0.9 J / cm ² , l _t is 69.7 ± 8.7㎛, and F _th (l _t ) is 25.3 ± 13.9 J / cm ² )

 Eyeball, retina, blood vessel, femtosecond laser, single pulse, removal

Description

Ultrafast Laser Apparatus for Selective Ablation of Ocular Biosubstance}

The present invention relates to a device for precisely and safely removing the biological material constituting the eye using a laser, and more particularly, by using a single pulse femtosecond laser by the relationship between the laser beam fluence and the removal depth. A device for removing a biological material.

Rapid advances in laser technology have resulted in the emergence of exciting and feasible new laser surgical techniques. In particular, high-tech lasers are easily used for tissue transaction, ablation and coagulation surgery by focusing lasers on small lesions. This potential characteristic of laser beams has already been carried out in multicenter clinical trials to ensure feasibility in vitreoretinal surgery.

Retinal resection using the first laser technique was attempted with a Nd: YAG laser, and resection of the vessel wall was not possible before the introduction of the 2940 nm: YAG laser wavelength.

Clinical trials with relatively long pulsed laser beams have been tried in a variety of retinal surgeries, but these systems have caused considerable damage to the retinal tissue and are not suitable for selective and regenerative excision of the Inner Limiting Membrane (ILM). Did.

In vitro experiments with Er: YAG laser surgery showed that retinal ablation was less than 4 microns, but thermal changes revealed more than 70 micron tissue damage from the surface of the ablation zone.

Epidermal retinal treatment on the normal retinal surface is stripped with microforceps. However, this technique is often not completely removed from the retina because the retina is strongly attached. During retinal resection, the contractile force of the retina causes the pigmented epithelial cells, the main cause of proliferative diabetic retinopathy, to be exposed to the vitreous, resulting in gaps in the retina.

A 193 nm ArF excimer laser has also been reported to cut accurately and reproducibly the formation of tissues in the fluid environment of the animal eye and the patient's eye, but limited precision and significant damage due to relatively long continuous laser pulses have been reported. Occurs and does not implement partial or selective retinal resection that requires a high degree of precision.

In order to overcome this damage, several experiments have been attempted through intraocular surgery in intraocular surgery using infrared laser sources such as carbon dioxide, Er: YAG, and Holmium: YAG. However, significant secondary thermal damage has been reported around tissues under the influence of significant thermal and mechanical shocks.

On the other hand, processing using ultrafast lasers amplified in the field of organic / inorganic materials has recently attracted much attention. These ultrafast lasers offer less thermal damage and provide higher precision than traditional tens of nanosecond long continuous wave lasers. Ultrafast lasers are known to be well suited for direct micromachining of materials because of the fast pulses of energy depletion and the non-contact nature of the materials and the micromachining of the material to minimize mechanical and thermal deformation.

The ablation threshold, F _th (J / cm ² ) in laser ablation, refers to the minimum thermal exposure required for effective material removal. The fluence threshold determines the appropriate precision of the laser used for tissue ablation and finer ablation. In general, it is necessary to lower the threshold for focusing ultrafast laser pulses on materials in order to minimize light damage in the immediate vicinity of the resected area.

The light of a powerful ultrafast laser beam causes multiphoton stimulation on the target material, and since the duration of the laser pearl is shorter than a constant vibration relaxation time of approximately several picoseconds, the energy absorbed by the material does not thermally diffuse into the region of the adjacent material. Will be transported electronically. As a result, thermal damage around tissues is minimized, and biological tissues will not be affected by damage caused by photoacoustic shock waves. This effectively allows for a fs-laser surgical process non-thermal. High density free electrons form a local plasma of the target material. This heated plasma formation also causes permanent damage even in submicron internal cells. For this reason, ultrafast lasers can be used for precise tissue resection treatment by minimizing thermal damage or impact pressure to biological tissues such as retina and neovascularization very specifically.

An object of the present invention for solving the above problems is to significantly reduce the damage and surgical-induced disorders of the surrounding tissues compared to the conventional laser surgery or drug therapy to remove the ocular biomaterial, free from mechanical thermal damage In addition, the present invention provides a device capable of selectively and selectively removing only a region to be removed.

An apparatus for removing a biological material using a laser according to the present invention is a device for removing a biological material constituting an eye using a laser, the laser light source generating a laser beam; An optical system that focuses the laser beam and irradiates the biological material; A stage for controlling the position of the biomaterial; And a laser controller for adjusting fluence of the laser beam generated from the laser light source, wherein the laser controller adjusts the fluence of the laser beam according to Equation 1 below. It is characterized by controlling the removal depth of the.

(Equation 1)

If F _th (l _o ) ≤ F <F _th (l _t ): L = l _o ln (F / F _th (l _o ))

If F _th (l _t ) ≤ F: L = l _t ln (F / F _th (l _t ))

Where L is the removal depth in μm, F is the fluence of the laser beam in J / cm ² , l _o is 8.2 ± 2.2 μm, and F _th (l _o ) is 2.2 ± 0.9 J / cm ² , l _t is 69.7 ± 8.7㎛, and F _th (l _t ) is 25.3 ± 13.9 J / cm ^2. )

Equation 1 is a relationship between the laser beam fluence and the depth damaged by the laser beam (the depth removed and damaged, L) when removing the biological material constituting the eyeball, when irradiating the laser beam to the biological material.

In detail, Equation 1 shows that in removing the biological material constituting the eyeball, the main damage mechanism varies depending on the size of the fluence in the log plot of the removal depth L and the beam fluence F by the laser beam. It means that the removal depth (L) and the fluence (F) are divided into two regions with different dependencies, and the damage mechanism by the laser beam at the fluence of F _th (l _t ) = 25.3 ± 13.9 J / cm ² ( mechanism), and at low laser beam fluence (F _th (l _o ) ≤ F <F _th (l _t )), the removal depth (L) and fluence (F) are L = l _o ln (F / F _th (l _o )), l _o has a relation of 8.2 ± 2.2 μm, F _th (l _o ) is 2.2 ± 0.9 J / cm ² , and high laser beam fluence (F _th (l _t ) ≤ F) In the _equation , L = l _t ln (F / F _th (l _t )), l _t is 69.7 ± 8.7㎛, and F _th (l _t ) is 25.3 ± 13.9 J / cm ² .

At this time, the F _th (l _o ) = 2.2 ± 0.9 J / cm ² is the minimum fluence for damaging the biological material constituting the eye, characteristically damage to the inner limiting membrane (ILM; Inner Limiting Membrane) of the retina Minimum fluence to give.

As described above, the removal apparatus according to the present invention can selectively remove only a specific material layer without damaging the underlying layer of the biological materials constituting the eyeball by precisely controlling the removal depth according to Equation 1 above.

The removal device according to the present invention includes an external input device for receiving location-specific removal data that is location-specific removal depth of a biomaterial to be removed; A memory in which the location-specific removal data and the relation 1 are stored; A microprocessor interlocked with the laser controller, the memory, and the stage; And a monitoring unit for monitoring the biological material, wherein the microprocessor is configured to automatically control the laser control unit and the stage based on positional removal data stored in the memory and Equation 1 above. .

When the thickness of the material layer to be removed varies from place to place within the eyeball among biological materials constituting the eyeball, the microprocessor receives the positional removal data (stored in a computer-readable recording medium), which is the depth-specific removal depth information. The laser controller and the stage are automatically controlled to adjust the fluence according to the removal depth of the biomaterial to be removed and the position of the biomaterial to be precisely and safely removed.

The removal device according to the present invention monitors the eye tissue including a stage and a target for removing the focusing object (object to which the laser beam is focused and irradiated) including an optical system and an eye for focusing the laser beam from the light source. It is preferably configured to include a monitoring unit and a laser control unit connected to the light source to adjust the fluence of the laser beam generated from the light source.

Preferably, the light source is a femtosecond laser in the near infrared region, and the optical system is adopted to process and adjust a path of the laser beam generated from the light source, and may include all of the conventional laser beam optical systems. Optical filters, including dichroic mirrors, objective lenses, and notch filters that selectively reflect light according to the pulsed wavelength, can be used to control and focus paths of pure short wavelength laser beams, and to provide fast optical Only a single pulse can be extracted from the pulse train of the laser beam using the shutter.

The stage is adopted to control the irradiation position setting of the laser beam for accurate laser beam irradiation to the site where the object to be removed in the eye, the stage is a three-axis direction (X, Y, Z) perpendicular to each other Independently movable, the stage is preferably provided with a fixing portion for fixing the treatment target including the eye to a specific position of the stage.

In order to more precisely control the irradiation position setting of the laser beam, it is preferable to include a monitoring unit for observing the tissue including the object to be removed in real time in a real-time image. The monitoring unit may use a general confocal imaging device as a real-time imaging device, and may be provided with a charge coupled device (CCD) camera that detects a photoluminescence signal split by a beam splitter.

The laser control unit is employed to control the fluence of the laser beam, the laser control unit is used for the normal laser beam fluence control, the wavelength conversion device of the laser beam, the direction of the laser beam and It may include all the devices for controlling the size of the beam, for example, the intensity of the laser beam can be adjusted using a neutral density filter (neutral density filter).

The input device is a conventional input device connected to a computer readable medium (eg, an external storage memory, an optical disk, a magnetic recording medium, etc.) to provide data stored in the medium to the microprocessor.

In this case, the stage, the laser control unit, the monitoring unit, and the optical system is preferably controlled in conjunction with a control program driven in a microprocessor, the position-specific removal data stored in the memory and the equation 1 also loaded in the microprocessor Preferably used as data of the control program.

In order to perform precise removal according to Equation 1 without damaging the tissue which is not to be removed, the focus of the laser beam is preferably a biological material to be removed.

Characteristically, the laser beam is a laser beam in the near infrared (NIR) region and the laser beam is a femtosecond single pulse.

According to the present invention, a femtosecond single pulse laser beam is irradiated to a biomaterial to be removed, and thus thermal damage to the surrounding material to be removed is extremely small and has a very high precision when removing a long continuous wave laser of several tens of nanoseconds.

Preferably the pulse width of the femtosecond single pulse laser beam is between 100 and 200 fs.

The wavelength of the laser beam is 780 to 840 nm so as not to damage the biomaterial of the eye that exists in the movement path of the laser beam to the biological material to be removed upon irradiation of the laser beam.

The maximum value of the laser beam fluence controlled by the laser control unit is 99.4 (J / cm ² ), and the maximum value is the inner layer of the retina (IPL; inner plexiform layer) and the inner granule layer (INL). ), An outer retinal layer (OPL; Outer Plexiform Layer), an outer layer (ONL; Outer Nuclear Layer), and the outer layer (OLM: Outer Limiting Membrane) to remove the retinal layer.

Peeling or ablation is characterized by the removal of the biological material according to the invention.

The biological material to be removed includes intraocular blood vessels including choroidal capillaries and arterial branch blood vessels in the center of the retina; Or the retina, and when the object to be removed is the retina, the amacrine cell layer (ACL), inner limiting membrane (ILM), or ganglion cell layer (GCL) in the retina having a multilayer structure. Of course, you can selectively remove only up to a specific layer.

In particular, the laser beam fluence controlled by the laser controller is 12 to 16 J / cm ² , and the biomaterial to be removed is a ganglion cell layer (GCL) of the retina.

In particular, the laser beam fluence controlled by the laser controller is 90 to 99.4 J / cm ² , and the biomaterial to be removed is an outer limiting membrane (OLM) of the retina.

The device according to the present invention can selectively and precisely remove the biological material constituting the eyeball, and has an advantage of having extremely low thermal damage and very high precision when removing the surrounding biological material. In addition, by precisely controlling the removal depth using the removal depth relationship according to the laser beam fluence, there is an advantage in that only a specific material layer can be selectively removed without damaging the underlying layer of the biological materials constituting the eye.

Hereinafter, a removal apparatus of the present invention will be described in detail with reference to the accompanying drawings. The drawings introduced below are provided by way of example so that the spirit of the invention to those skilled in the art can fully convey. Accordingly, the present invention is not limited to the drawings presented below and may be embodied in other forms. Also, throughout the specification, like reference numerals designate like elements.

At this time, if there is no other definition in the technical terms and scientific terms used, it has a meaning commonly understood by those of ordinary skill in the art to which the present invention belongs, the gist of the present invention in the following description and the accompanying drawings Descriptions of well-known functions and configurations that may be unnecessarily blurred are omitted.

Hereinafter, the relationship between the laser beam fluence and the removal depth according to the present invention will be described using the extracted pig eye.

1 is a diagram showing an experimental device for removing blood vessels in the retina or eye of a pig, wherein the light source is Regenerative-amplified Ti: Sapphire (810 nm) having a pulse width of about 150 fs at a repetition rate of 1 kHz (Quantronix, USA). It consisted of a laser. The laser beam was focused on the retina surface using an objective lens (NA = 0.4). The diameter of the laser beam is about 1.3 micrometers. The retinal tissue was fixed to an automatic XY translation stage, which was used to position the sample to focus new areas of tissue at each laser pulse. An optical shutter with a response speed of less than 0.6 ms was used to accurately focus a single laser pulse on the sample. The laser fluence used in this experiment ranges from 0.7 J / cm ² to 99.4 J / cm ² on the surface of the tissue.

A total of 13 pig eyes were used, each eye was resected with 20-25 lasers, and the retinal surface and retinal vessels were irradiated at 100 micrometer intervals. All experiments used a single laser pulse.

Pig eyes were harvested from slaughterhouses and stored in HBSS (Hank's Balanced Salt Solution, Welgene Inc. Korea) at 4 ° C. In cold HBSS, the eyeballs immediately behind the ora-serrata, cornea, iris and lens were incised and the viscous vitreous humour was removed. After removing the retina from the pigment epithelial cells, a retinal piece of about 3 × 5 mm ² size was prepared by placing it on a filter paper (Whatman, UK). During the experiment, all the retinal fragments were covered with 100 microliters of vitreous fluid to prevent the retina from drying out and bring it closer to in vivo. And all experiments were completed within 3 hours after slaughter.

To obtain a scanning electron microscopy (SEM) picture, a retinal tissue of about 10 x 10 mm ² was placed on the cover glass and then resected by laser. solution was fixed for 1 hour, 30 minutes in 0.5% fixative, 30 minutes in 1.0% fixative, 30 minutes in 1.5% fixative and 1 hour at 2.0%. The fixed tissues were completely dried within 4-6 hours at room temperature and then thinly coated with platinum.

Immediately after excision using a laser, the retinal fragments were fixed for 1 hour in a 2% fixative solution at 4 ° C. The fixed sample was placed in Jung's Tissue Freezing medium for 1 hour at room temperature. And then stored frozen at -20 ℃ 4-6 hours. Transverse sections were made to a thickness of 15 to 20 micrometers using a cold sectioning device (Leica, CM1850, Germany). More than 20-25 sections in each retinal sample were characterized by laser damage. In order to observe the inner membrane and blood vessel wall of the retina damaged by the laser, hematoxylin and eosin-red (Haemotoxylin & Eosin Red, H & E) were stained as shown in FIG. 2.

Stained tissue sections were observed using an optical microscope (Zeiss, Axioscope) at high resolution, and then photographed. To determine the percentage of retinal damage, three replicates were performed with at least 100 samples in each fluence range.

Similarly, the retinal vessel wall was subjected to five replicates of 874 samples in the laser beam fluence range of 1.4 J / cm ² to 99.4 J / cm ² .

The depth of retinal resection was measured by using a single pulse of ultrafast laser.

Removal of the retina

Experiment to confirm retinal ablation and ablation and subsequent secondary damage and other side effects by irradiating ultrafast laser beam to the retina in a wide pulse fluence of 0.7 J / cm ² to 99.4 J / cm ² in a single pulse. Was performed.

3 is an optical image of a laser treated tissue section observed by H & E staining by irradiating a single femtosecond laser pulse to the retina. In FIG. 3, the horizontal photographs are photographs of consecutive sections of the same sample, and the photographs of the springs where higher fluences are irradiated downward on the vertical lines, in which the scale bar is 100 micrometers. 3 clearly shows high precision retinal layer ablation by single pulse femtosecond laser beam irradiation.

The breakdown of the internal boundary membrane occurred at a visual probability of about 20% in the 3.6 J / cm ² laser fluence, but the retinal surface was also changed in the 1.4 J / cm ² laser fluence. These experiments showed that the minimum laser fluence (Fth (l _o )) for retinal tissue resection was 2.2 ± 0.9 J / cm ² .

The laser fluence of selectively resecting the ganglion cell layer (GCL) without any damage under the amacrine cell layer (IPL) was 12-16 J / cm ² , in detail 13-15 J / cm ² . In more detail, it was 14-14.5 J / cm <^2> .

Furthermore, the laser fluence of a high single femtosecond laser pulse of 90 to 99.4 J / cm ² is in detail a fluence of 95 to 99.4 J / cm ² , more specifically a fluence of 98 to 99.4 99.4 J / cm ² . Inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and outer limiting membrane (OLM) It was found that the retinal layer consisting of) is excised.

These experimental results indicate that even though the laser beam focuses on the surface of the retina, it is possible to selectively remove a specific layer by using a single pulse of the ultrafast laser on various layers of the retinal tissue.

All sections of resected retinal tissues using ultrafast laser showed two aspects: randomly unchanged sections and clearly resected sections. 4 is a graph showing the probabilities shown in each group. It can be seen that there is a positive correlation between the level of laser fluence and the probability of damage to the retinal layer, and the difference between the secondary damaged section and the excised tissue section by the ultrafast laser beam is measured to determine the Excision depth of porcine ocular retina was measured.

FIG. 5 is a half log equation plot between the fluence of the irradiated single pulse femtosecond laser beam and the measured ablation depth. As can be seen in FIG. 5, Equation 1 above is mainly used to remove the biological material constituting the eyeball, depending on the fluence size in the log plot of the removal depth (L) and the beam fluence (F) by the laser beam. It can be seen that the damage mechanism is divided so that the removal depth (L) and the fluence (F) are divided into two regions with different dependencies, and the boundary flu with F _th (l _t ) = 25.3 ± 13.9 J / cm ² It can be seen that the damage mechanism caused by the laser beam in the Earth is different.

After dividing the result of FIG. 5 into two regions and linearizing, at a low laser beam fluence (F _th (l _o ) ≤ F <F _th (l _t )), the removal depth L and the fluence F are L = l _o ln (F / F _th (l _o )), l _o is 8.2 ± 2.2 μm, F _th (l _o ) is 2.2 ± 0.9 J / cm ² , and high laser beam fluence (F _th For (l _t ) ≤ F), L = l _t ln (F / F _th (l _t )), l _t has a relationship of 69.7 ± 8.7㎛, and F _th (l _t ) has 25.3 ± 13.9 J / cm ² It can be seen.

In this case, F _th (l _o ) = 2.2 ± 0.9 J / cm ² is the minimum fluence for damaging the inner limiting membrane (ILM) of the retina or the inner limiting membrane (ILM) of the blood vessel.

L _o is the optical transmission depth obtained experimentally and l _t is the electronic heating depth obtained experimentally. Relatively, the heating depth of the retinal tissue was about 8.5 times higher than the depth of optical ablation.

The above relation is obtained on the basis of accurate experimental results, and serves as a reference for controlling the laser beam fluence according to the removal depth when the biological material constituting the eye such as the retina and blood vessel constituting the eye is removed.

As can be seen from the above derived relationship, the high laser fluence retinal ablation mechanism cannot be explained by the optical penetration depth. As shown in FIG. 6, the surface of the retina irradiated with high laser fluence of 99.4 J / cm ² (FIG. 6 (a)) is the surface of the retina irradiated with low fluence of 7.1 J / cm ² (FIG. 6 (b). Compared to)) it was quite rough. Based on the change in the slope of the semi-logograph with the depth of ablation, it can be seen that the electronic thermal diffusion method plays an important role in ultrafast laser ablation at high laser fluences above 25.3 J / cm ² . This high laser fluence region has an electronic thermal depth (l _t ) rather than an optical penetration depth (l _o ), and with Fth (l _t ) a laser fluence threshold corresponding to the electronic thermal depth (l _t ) is obtained. To remove phosphorus, very accurate laser fluence must be adjusted.

Ablation and ablation thresholds along the laser pulse width are well known for materials such as transparent and soft biological tissues, such as silicon substrates and corneal stromas. The ablation threshold decreases with decreasing pulse width, with little change between 100 fs and 1 ps for corneal interstitial (D. Gigu┰re, G. Olivi┰, F. Vidal, S. Toetsch, G). Girard, T. Ozaki, JC Kieffer, O. Nada, and I. Brunette, "Laser ablation threshold dependence on pulse duration for fused silica and corneal tissues: experiments and modeling," J. Opt. Soc. Am. A 24, 1562-68 (2007)). Therefore, the ablation threshold of the ultrafast laser beam is increased and the dissolved silicon dioxide and calcium fluoride (CaF ₂ ) have a constant wavelength of about 3 J / cm ² at 1000 nm (TQ Jia, HX Chen, M). Huang, FL Zhao, XX Li, SZ Xu, HY Sun, DH Feng, CB Li, XF Wang, RX Li, ZZ Xu, XK He, and H. Kuroda, "Ultraviolet-infrared femtosecond laser-induced damage in fused silica and CaF ₂ crystals, "Phys. Rev. B 73, 054105 (2006)). In other biological tissues, such as corneal stroma, the outer layer of the retina is transmitted at 810 nm rather than under the photosensitive layer (PD Brazitikos, DJ D'Amico, MT Bernal, and AW Walsh, "Erbium: YAG laser surgery of the vitreous and retina, "Opthalmology 102, 278-290 (1995)). The chemical composition of the retina, therefore, may be quite similar to biological tissues, for example, with 70% water and 30% organic matter (A. Vogel, and V. Venugopalan, "Mechanism of pulsed laser ablation of biological tissues", Chem). Rev. 103, 577-644 (2003). This supports that the retinal ablation mechanism and ablation threshold are similar to corneal stroma.

Various microresections, which are increasing in macular degeneration, require the development of accuracy, safety, and versatile instrumentation with minimal invasion. Traditional methods of removing the internal limiting membrane cause staining of the retina by staining Indocyanine Green, which is known to cause damage to the retina itself, but the present invention does not damage the lower and surrounding tissues. Only the inner boundary layer can be selectively removed.

The thickness of the inner boundary membrane, which is essentially the lowermost layer of the Muller cells of the retina, is 6 μm to 10 μm. The internal border thickness is the thinnest in the center and fovea region of the retina. However, the thickness increases toward the retina of the retina (H. Hoerauf, A. Brix, J. Winkler, G. Droege, C. Winter, R. Birngruber, H. Laqua, and A. Vogel, "A Photoablation of inner limiting membrane and inner retinal layers using the Erbium: YAG-laser: An in vitro study, "Lasers in Surgery and Medicine 38 (1), 52-61 (2006)). In addition, the internal limiting membrane also appears above the blood vessels of the retina. In order to selectively ablate only the inner boundary membrane without any change underneath the layer, the energy delivered by the laser beam must be localized in a thin layer without a pronounced dispersion of the energy deposited in other retinal areas, and the femtosecond single pulse laser according to the invention This can be achieved by investigating a specific biomaterial layer (e.g., internal boundary membrane) whose thickness varies according to location very precisely by deriving the removal (ablation) depth relation according to the fluence to a transparent material such as retinal tissue. The bay can be selectively and safely removed completely.

In the relation derived as described above, l _o means the optical penetration depth, Fth (l _o ) means the ablation threshold of the laser fluence. If multiphoton absorption plays an important role in the steric stimulation of the material, the optical penetration depth would have been controlled by nonlinear absorption rather than linear optical absorption. Therefore, the optical penetration depth l _o derived from the present invention differs from the optical absorption range of the retinal tissue at a wavelength of 810 nm in the literature. Comparing the thickness of the internal boundary membrane of the porcine retina with the optical penetration depth derived from the present invention, the femtosecond monolithic membrane according to the present invention is similar because the optical penetration depth (l _o ) of 8.2 ± 2.2 μm is similar to the thickness of the internal boundary membrane of the retina. It can be seen that by irradiating the pulsed laser beam and adjusting the laser fluence, only the internal boundary membrane can be selectively excised without damaging the underlying or surrounding tissue.

In the present invention as described above has been described by specific embodiments and limited embodiments and drawings, but this is only provided to help a more general understanding of the present invention, the present invention is not limited to the above embodiments, the present invention Those skilled in the art can make various modifications and variations from this description.

Therefore, the spirit of the present invention should not be limited to the described embodiments, and all of the equivalents or equivalents of the claims as well as the claims to be described later will belong to the scope of the present invention. .

1 is a view showing an experimental apparatus for removing the retina or intraocular blood vessels for the pig eye,

2 is a retinal cross-sectional photograph of intraocular blood vessels and multilayer structure,

Figure 3 is a slice photograph of the retina according to the irradiated femtosecond single-pulse laser beam fluence,

4 is a diagram showing the probability of damage to the internal boundary film (ILM) of the retina according to the irradiated femtosecond single-pulse laser beam fluence,

5 is a diagram showing the removal depth of the retina according to the irradiated femtosecond single pulse laser beam fluence,

Figure 6 is a scanning electron micrograph of (in FIG. 6 (a) In the case of ^{99.4 J / cm 2, 6 (} b Fig.) 7.1J / cm ²⁾ is irradiated single femtosecond pulsed laser beam fluence retina corresponding to the surface.

Claims (12)

A device for removing the biological material constituting the eyeball using a laser, A laser light source for generating a laser beam; An optical system that focuses the laser beam and irradiates the biological material; A stage for controlling the position of the biomaterial; And A laser controller configured to adjust fluence of the laser beam generated from the laser light source; It is configured to include, The apparatus of claim 1, wherein the laser controller controls the removal depth of the biomaterial by adjusting the fluence of the laser beam by Equation 1 below. (Equation 1) If F _th (l _o ) ≤ F <F _th (l _t ): L = l _o ln (F / F _th (l _o )) If F _th (l _t ) ≤ F: L = l _t ln (F / F _th (l _t )) Where L is the removal depth in μm, F is the fluence of the laser beam in J / cm ² , l _o is 8.2 ± 2.2 μm, and F _th (l _o ) is 2.2 ± 0.9 J / cm ² , l _t is 69.7 ± 8.7㎛, and F _th (l _t ) is 25.3 ± 13.9 J / cm ^2. ) The method of claim 1, The removal device is An external input device for receiving location-specific removal data that is a location-specific removal depth of a biomaterial to be removed; A memory in which the location-specific removal data and the relation 1 are stored; A microprocessor interlocked with the laser controller, the memory, and the stage; And A monitoring unit for monitoring the biomaterial; Consists of more, And the microprocessor automatically controls the laser controller and the stage based on the positional removal data stored in the memory and the equation 1. The method of claim 1, The focus of the laser beam is a biological material removal apparatus using a laser, characterized in that the biological material to be removed. The method of claim 1, And the laser beam is a laser beam in a near infrared region. The method of claim 4, wherein And the laser beam is a femtosecond single pulse. The method of claim 5, Pulse width of the laser beam is 100 to 200 fs apparatus for removing a biological material using a laser. The method of claim 6, The wavelength of the laser beam is a biological material removal apparatus using a laser, characterized in that 780 to 840nm. The method of claim 1, And a maximum value of the laser beam fluence controlled by the laser controller is 99.4 (J / cm ² ). The method of claim 1, Apparatus for removing a biological material using a laser, characterized in that the peeling or ablation occurs by the removal of the biological material. The method according to any one of claims 1 to 9, The biological material removal apparatus using a laser, characterized in that the biological material to be removed is the retina. The method of claim 10, The laser beam fluence controlled by the laser controller is 12 to 16 J / cm ² , and the biological material to be removed is a Ganglion cell layer (GCL) of the retina. Device. The method of claim 10, The laser beam fluence controlled by the laser controller is 90 to 99.4 J / cm ² , and the biomaterial to be removed is an outer limiting membrane (OLM) of the retina. Removal device.

Images