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1.发明申请Method for transferring molecules in vital cells by means of laser beams and arrangement for carrying out said method 有权用于通过激光束转移生物细胞中的分子的方法和用于执行所述方法的装置公开(公告)号：US20060141624A1
公开(公告)日：2006-06-29
申请号：US10515558
申请日：2003-05-22
申请人： Karsten Koenig , Uday Tirlapur
发明人： Karsten Koenig , Uday Tirlapur
IPC分类号： C12N15/00
摘要： The invention relates to an optical method for targeted transfer of molecules, preferably of DNA, RNA, peptides, amino acids and proteins, into vital cells by means of laser radiation and to an arrangement for implementing the method. The object of the invention, to find a novel possibility for targeted molecule transfer into the interior of vital cells, particularly the transfer of DNA, RNA, peptides, amino acids and proteins, which achieves a high transfer efficiency while extensively excluding destructive side effects such as a lethal effect on a treated cell, is met according to the invention in that cellular membranes are opened transiently for the molecule transfer by multiple laser pulses in the microjoule range or less and a pulsed, near-infrared laser beam with a pulse width in the femtosecond range is directed in each instance to a submicrometer spot of a membrane of the vital cell for an irradiation period of less than one second.
摘要翻译： 本发明涉及通过激光辐射将分子（优选DNA，RNA，肽，氨基酸和蛋白质）靶向转移到活细胞中的光学方法以及用于实施该方法的装置。 本发明的目的是为了找到靶向分子转移到活细胞内部的新型可能性，特别是DNA，RNA，肽，氨基酸和蛋白质的转移，其实现了高转移效率，同时广泛地排除了破坏性副作用 作为对经处理的细胞的致死作用，根据本发明，通过在微焦耳范围以内的多个激光脉冲和短脉冲的近红外激光束瞬时打开细胞膜以进行分子转移，脉冲宽度为 飞秒范围在每种情况下都被引导到生命细胞膜的亚微米点，其辐照时间小于1秒。
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公开(公告)号：US06528802B1
公开(公告)日：2003-03-04
申请号：US09806375
申请日：2001-06-01
IPC分类号： G01N2726
CPC分类号： C12Q1/6841 , C12Q2563/107
摘要： A method for optical excitation of fluorophore-labeled DNA and fluorophore-labeled RNA, particularly of specific localizations of DNA and RNA labeled by fluorescence in situ hybridization (FISH). It is the object of the method to make possible in a simple manner a high-contrast simultaneous excitation of a plurality of FISH fluorophores which have different fluorescence characteristics and are to be detected and displayed three-dimensionally. The excitation and detection of fluorophores at a depth of the biological material greater than 100 micrometers must be ensured. The FISH fluorophores and DNA markers are excited to fluorescence by a multiphoton excitation simultaneously by pulsed and non-pulsed radiation at a single wavelength in the range between 700 nm to 1000 nm, preferably between 760 nm and 820 nm. A total of 20 commercially available FISH fluorophores and DNA markers were tested. Fluorophores which were excited simultaneously by multiphoton excitation were detected in all tested cases.
摘要翻译： 用于光激发荧光团标记的DNA和荧光团标记的RNA的方法，特别是通过荧光原位杂交（FISH）标记的DNA和RNA的特异性定位的方法。 该方法的目的是以简单的方式使得具有不同荧光特性并将被三维检测和显示的多个FISH荧光团的高对比度同时激发成为可能。 必须确保在生物材料的深度大于100微米的荧光团的激发和检测。 通过在700nm至1000nm之间，优选760nm至820nm之间的范围内的单一波长的脉冲和非脉冲辐射同时通过多光子激发而将FISH荧光团和DNA标记激发至荧光。 共测试了20种市售的FISH荧光团和DNA标记。 在所有测试的情况下都检测到通过多光子激发同时激发的荧光团。
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3.发明申请METHOD AND ARRANGEMENT FOR HIGH-RESOLUTION MICROSCOPE IMAGING OR CUTTING IN LASER ENDOSCOPY 有权激光内窥镜中高分辨率显微镜成像或切割的方法和装置公开(公告)号：US20080081950A1
公开(公告)日：2008-04-03
申请号：US11861472
申请日：2007-09-26
申请人： KARSTEN KOENIG , Andrei TCHERNOOK
发明人： KARSTEN KOENIG , Andrei TCHERNOOK
CPC分类号： A61B5/415 , A61B1/00172 , A61B5/0068 , A61B5/0084 , A61B5/418 , A61B18/20 , G02B23/2423 , G02B23/2469 , G02B26/101
摘要： The invention is directed to a method and an arrangement for high-resolution microscopic imaging in laser endoscopy based on laser-induced object reaction radiation and for performing microscopic cuts in biological tissue. In using multiphoton processes for endoscopic applications in biological materials with an accuracy of under one millimeter, radiation of a pulsed femtosecond laser is focused into an object by means of a transmission focusing optics unit comprising a transmission system and miniature focusing optics having a high numerical aperture greater than 0.55 to trigger a local object reaction radiation in the micrometer to nanometer range, and the distal end of the transmission focusing optics unit is moved in at least two dimensions for highly spatially resolved scanning of the object and for transmitting object reaction radiation which is scanned in a locally progressive manner to an image-generating system with a photon detector. In an other embodiment the femtosecond laser radiation is energy enhanced is applied to the same transmission focusing optics unit to perform microendoscopic surgery in biological tissue.
摘要翻译： 本发明涉及一种基于激光诱导物体反应辐射和用于在生物组织中进行微观切割的激光内窥镜检查中的高分辨率显微成像的方法和装置。 在使用精密度在一毫米以下的生物材料内窥镜应用的多光子过程中，脉冲飞秒激光的辐射通过包括传输系统的传输聚焦光学单元和具有高数值孔径的微型聚焦光学器件聚焦到物体中 大于0.55以触发微米至纳米范围内的局部物体反应辐射，并且透射聚焦光学单元的远端在至少两个维度上移动，用于物体的高度空间分辨扫描并且用于传送物体反射辐射 以局部渐进的方式扫描到具有光子检测器的图像生成系统。 在另一实施例中，将飞秒激光辐射能量增强应用于相同的透射聚焦光学单元以在生物组织中执行微内窥镜手术。
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4.发明授权Method for the simultaneous dissection in specific positions of filiform organic molecular chains, in particular DNA 有权丝状有机分子链特别位置同时解剖的方法，特别是DNA公开(公告)号：US07263445B2
公开(公告)日：2007-08-28
申请号：US10450544
申请日：2001-12-12
CPC分类号： C12N15/10 , C12Q1/68 , Y10S977/81 , C12Q2563/155 , C12Q2523/313
摘要： The invention relates to a method for the simultaneous dissection in specific positions of filiform organic molecular chains, in particular DNA. The aim of the invention is to provided a method, by which a highly specific dissection can take place on certain sequences that can be freely selected and simultaneously on numerous filiform molecules. To achieve this, nanoparticles (1) are provided with a molecular chain (11) of any predeterminable sequence, which is selected to be complementary to a sequence of a molecule (2) that is to be dissected, said molecular chain(s) (11) is/are hybridised in the usual manner with the molecule, or specifically linked to said molecule in another manner and the nanoparticles (1) are subsequently subjected to a high-energy radiation of at least one wavelength, which can be absorbed by said nanoparticles (1).
摘要翻译： 本发明涉及一种用于在丝状有机分子链，特别是DNA的特定位置同时解剖的方法。 本发明的目的是提供一种方法，通过该方法可以在可以自由选择并同时存在于许多丝状分子上的某些序列上发生高度特异性的解剖。 为了实现这一点，纳米颗粒（1）被提供有任何可预定序列的分子链（11），其被选择为与被解剖的分子（2）的序列互补，所述分子链（ 11）以通常的方式与分子杂交，或以另一种方式特异性连接到所述分子，并且纳米颗粒（1）随后经受至少一个波长的高能辐射，其可被所述 纳米粒子（1）。
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公开(公告)号：US20160184135A1
公开(公告)日：2016-06-30
申请号：US14420619
申请日：2012-08-22
摘要： The invention relates to an eye-surgical laser apparatus, a use of said apparatus, and to a method for scanning the corneal tissue of an eye before or during eye surgery. The apparatus comprises optics that are adapted to focus a laser beam at a focus within a corneal tissue of an eye, and a detection element adapted to detect light that is formed, at the focus, as a frequency multiple and backscattered or forward emitted. Image information about the inner corneal tissue is then produced from the detected light.
摘要翻译： 本发明涉及一种眼外科激光装置，所述装置的使用以及在眼外手术之前或期间扫描眼睛的角膜组织的方法。 该装置包括适于将激光束聚焦在眼睛的角膜组织内的光学元件，以及适于检测在焦点处形成的作为频率倍数和反向散射或向前发射的光的检测元件。 然后从检测到的光产生关于内部角膜组织的图像信息。
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6.发明授权Method for transferring molecules in vital cells by means of laser beams and arrangement for carrying out said method 有权用于通过激光束转移生物细胞中的分子的方法和用于执行所述方法的装置公开(公告)号：US07892837B2
公开(公告)日：2011-02-22
申请号：US10515558
申请日：2003-05-22
IPC分类号： C12N15/87
摘要： The invention relates to an optical method for targeted transfer of molecules, preferably of DNA, RNA, peptides, amino acids and proteins, into vital cells by means of laser radiation and to an arrangement for implementing the method. The object of the invention, to find a novel possibility for targeted molecule transfer into the interior of vital cells, particularly the transfer of DNA, RNA, peptides, amino acids and proteins, which achieves a high transfer efficiency while extensively excluding destructive side effects such as a lethal effect on a treated cell, is met according to the invention in that cellular membranes are opened transiently for the molecule transfer by multiple laser pulses in the microjoule range or less and a pulsed, near-infrared laser beam with a pulse width in the femtosecond range is directed in each instance to a submicrometer spot of a membrane of the vital cell for an irradiation period of less than one second.
摘要翻译： 本发明涉及通过激光辐射将分子（优选DNA，RNA，肽，氨基酸和蛋白质）靶向转移到活细胞中的光学方法以及用于实施该方法的装置。 本发明的目的是为了找到靶向分子转移到活细胞内部的新型可能性，特别是DNA，RNA，肽，氨基酸和蛋白质的转移，其实现了高转移效率，同时广泛地排除了破坏性副作用 作为对经处理的细胞的致死作用，根据本发明，通过在微焦耳范围以内的多个激光脉冲和短脉冲的近红外激光束瞬时打开细胞膜以进行分子转移，脉冲宽度为 飞秒范围在每种情况下都被引导到生命细胞膜的亚微米点，其辐照时间小于1秒。
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公开(公告)号：US20090171325A1
公开(公告)日：2009-07-02
申请号：US12345412
申请日：2008-12-29
申请人： Karsten Koenig
发明人： Karsten Koenig
CPC分类号： A61F9/007
摘要： The invention relates to a process for minimally invasive to non-invasive optical treatment of tissues of the eye and also for diagnosis thereof and to a device for implementing this process. The object underlying the invention is to create a process and a laser arrangement for minimally invasive to non-invasive optical treatment in the interior of the eye, particularly of cases of defective vision, by ablation of tissue, said treatment being distinguished by a hitherto unattained high precision, with possible widths of incision in the range less than 2 μm, without a significant mechanical impairment of the surrounding tissue occurring that has been generated by photodisruption. The process and the arrangement are to be inexpensive and easy to operate. In addition, at the same time the arrangement is to enable a three-dimensional imaging of the tissue. This object is achieved by virtue of a process in which the ablation is effected by focused planar or spatial scanning while adhering to equal, in order of magnitude, focusing-point diameters and point spacings below 5 μm with a radiation within the spectral range from 500 nm to 1200 nm, whereby, by virtue of a pulse duration in the order of femtoseconds and an energy of the individual pulse in the order of nanojoules and below, the destruction of the tissue is substantially limited to the diameter of the point, and permanent changes by virtue of propagation of energy beyond this diameter are avoided. The invention can be applied in opthalmology.
摘要翻译： 本发明涉及一种用于微创光学治疗眼组织的微创方法，也涉及用于诊断眼科组织和用于实施该过程的装置的方法。 本发明的目的是为了通过消融组织创建一种用于在眼内部进行非侵入性光学治疗的最小侵入性的方法和激光装置，特别是缺损视力的情况下，所述治疗由迄今为止未知的 高精度，可能的切口宽度在小于2μm的范围内，而没有由光破坏产生的周围组织的显着的机械损伤。 该方法和装置应该便宜并且易于操作。 此外，同时该装置能够进行组织的三维成像。 该目的是通过以下过程来实现的：其中通过聚焦的平面或空间扫描来实现消融，同时按照等级，大小等于5微米的聚焦点直径和点间距等于500μm的光谱范围内的辐射 通过脉冲持续时间以毫秒以下的单位脉冲的次数和单个脉冲的能量，组织的破坏基本上限于点的直径，并且永久地 避免了超过该直径的能量传播的变化。 本发明可应用于眼科学。
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8.发明授权Method and arrangement for high-resolution microscope imaging or cutting in laser endoscopy 有权用于激光内窥镜检查的高分辨率显微镜成像或切割的方法和装置公开(公告)号：US08496579B2
公开(公告)日：2013-07-30
申请号：US11861472
申请日：2007-09-26
申请人： Karsten Koenig , Andrei Tchernook
发明人： Karsten Koenig , Andrei Tchernook
CPC分类号： A61B5/415 , A61B1/00172 , A61B5/0068 , A61B5/0084 , A61B5/418 , A61B18/20 , G02B23/2423 , G02B23/2469 , G02B26/101
摘要： The invention is directed to a method and an arrangement for high-resolution microscopic imaging in laser endoscopy based on laser-induced object reaction radiation and for performing microscopic cuts in biological tissue. In using multiphoton processes for endoscopic applications in biological materials with an accuracy of under one millimeter, radiation of a pulsed femtosecond laser is focused into an object by means of a transmission focusing optics unit comprising a transmission system and miniature focusing optics having a high numerical aperture greater than 0.55 to trigger a local object reaction radiation in the micrometer to nanometer range, and the distal end of the transmission focusing optics unit is moved in at least two dimensions for highly spatially resolved scanning of the object and for transmitting object reaction radiation which is scanned in a locally progressive manner to an image-generating system with a photon detector. In an other embodiment the femtosecond laser radiation is energy enhanced is applied to the same transmission focusing optics unit to perform microendoscopic surgery in biological tissue.
摘要翻译： 本发明涉及一种基于激光诱导物体反应辐射和用于在生物组织中进行微观切割的激光内窥镜检查中的高分辨率显微成像的方法和装置。 在使用精密度在一毫米以下的生物材料内窥镜应用的多光子过程中，脉冲飞秒激光的辐射通过包括传输系统的传输聚焦光学单元和具有高数值孔径的微型聚焦光学器件聚焦到物体中 大于0.55以触发微米至纳米范围内的局部物体反应辐射，并且透射聚焦光学单元的远端在至少两个维度上移动，用于物体的高度空间分辨扫描，并用于传送物体反射辐射 以局部渐进的方式扫描到具有光子检测器的图像生成系统。 在另一实施例中，将飞秒激光辐射能量增强应用于相同的透射聚焦光学单元以在生物组织中执行微内窥镜手术。
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