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WO2011028109A1 - Système et procédé pour réaliser une microscopie avec une lumière présentant un moment angulaire orbital - Google Patents

Système et procédé pour réaliser une microscopie avec une lumière présentant un moment angulaire orbital Download PDF

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Publication number
WO2011028109A1
WO2011028109A1 PCT/NL2010/050547 NL2010050547W WO2011028109A1 WO 2011028109 A1 WO2011028109 A1 WO 2011028109A1 NL 2010050547 W NL2010050547 W NL 2010050547W WO 2011028109 A1 WO2011028109 A1 WO 2011028109A1
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WIPO (PCT)
Prior art keywords
light beam
sample
microscopy
angular momentum
orbital angular
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English (en)
Inventor
Gert Wim 't Hooft
Gerhardus Wilhelmus Lucassen
Johannes Petrus Woerdman
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Universiteit Leiden
Koninklijke Philips NV
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Universiteit Leiden
Koninklijke Philips Electronics NV
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    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G02B21/08—Condensers
    • G02B21/14—Condensers affording illumination for phase-contrast observation
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes

Definitions

  • the invention relates to a system and a method for performing microscopy, and more particularly to a microscopy system comprising a light source for generating a first light beam, a sample area for accommodating a sample, a detector for detecting a second light beam generated by the sample in response to the first light beam and an optical assembly for focusing the first light beam on the sample area and for focusing the second light beam on the detector.
  • Collagen fibres are made of bundles of long collagen protein molecules. They can be found inside and outside of biological cells and provide structure to cells.
  • the collagen molecule or tropocollagen is about 300 nm long and 1.5 nm in diameter and comprises three polypeptide strands with a left-handed helix. Together these three helices form a right-handed coiled coil or a triple helix stabilized by numerous hydrogen bonds.
  • Collagen structures may have different three- dimensional structures and are identified by their so-called type number. Different collagen types may be found in different parts in the human body or in different phases of biological processes. For example, type I collagen can be found in skin, tendon, vascular, ligature, organs, and/or bones, while type IV collagen is found in the bases of the cell basement membranes.
  • Collagen may change its helical structure from one type to another type, for example during the process of scarring, wound healing or the formation of bones.
  • the structure of collagen may therefore be studied for diagnostic purposes, especially in the area of dermatology, ophthalmology and oncology.
  • the structure of molecules may be studied with a microscopy technique in which an excitation light beam is scattered by a sample and the scattered light is detected.
  • linear scattering also non-linear scattering processes may be used, such as the second harmonic generation process, in which the wavelength of the scattered light is half a wavelength of the excitation light.
  • the scattered light will be detected and measured during a sampling time and on the bases of these measurements an image of the sample may be constructed.
  • the efficiency of the scattering process may be defined as the ratio of the intensity of the scattered light beam and the intensity of the excitation light beam.
  • the scattering process may not be very efficient, and therefore the contrast of the images may be low and/or the sampling times may be long.
  • a microscopy system comprising a light source arranged for generating a first light beam, a sample area arranged for
  • the light source is arranged for generating the first light beam with an orbital angular momentum.
  • the light source, the sample area, the detector and the optical assembly may be arranged or placed on a frame.
  • the light generation processes in response to the first light beam are more efficient when the molecules of the sample receive a first light beam with an orbital angular momentum.
  • the contrast of the images improves and the sampling time decreases.
  • the characteristics of the first light beam preferably match more or less the characteristics of the molecules of the sample.
  • the second light beam is generated by scattering of the first light beam in the sample.
  • Another advantage of providing a first light beam with an orbital angular momentum may be that it enables the study of the characteristics of the sample, for example the pitch, the handedness and the direction of a helical structure in the sample.
  • the orbital angular momentum may be in the range of 1 -100 per photon.
  • the microscopy system comprises said sample to be examined, the sample comprising at least one molecular helical structure.
  • the microscopy system further comprises a sample holder arranged in the sample area, wherein the sample holder is holding said sample.
  • the sample holder may be arranged or placed on the frame.
  • the wave front of a light beam with an orbital angular momentum has a helical structure, it may be advantageous to use a first light beam with an orbital angular momentum to excite one or more molecules with a helical structure, since their
  • the detector is arranged for selectively detecting a wavelength of the second light beam, being equal to half a wavelength of the first light beam or being equal to the wavelength of the first light beam.
  • the scattering process may be a linear or a non-linear process, for example second harmonic generation.
  • a linear scattering process the wavelength of the second light beam equals the wavelength of the first light beam.
  • the wave length of the second light beam equals half the wavelength of the first beam.
  • the first light beam comprises electromagnetic radiation with wavelengths in the range of 700 - 1000 nm
  • the detector is arranged for selectively detecting the second light beam with wavelengths in the range of 700 - 1000 nm and/or of 350-500 nm.
  • Light with a wavelength in the range of 700 - 1000 nm provides deep penetration of biological tissue.
  • especially collagen can be examined very well with wavelengths in the range of 700 - 1000 nm for the first light beam.
  • a wavelength of about 800 nm for the first light beam appears very advantageous for amongst others collagen.
  • the microscopy system further comprises an orbital angular momentum adjuster for adjusting the orbital angular momentum of the first light beam, and/or a propagation direction adjuster for adjusting a mean propagation direction of the first light beam with respect to the sample area. Since the light generation processes in sample in response to the first light beam appear to be more efficient when the characteristics of the first light beam match the characteristics of the molecules of the sample, it is advantageous to be able to change the characteristics of the first light beam depending on the sample to be examined.
  • the detector is arranged for providing a detection signal in response to the detection of the second light beam.
  • this detection signal is representative for the second light beam.
  • the microscopy system further comprises a control unit arranged for receiving the detection signal and controlling the orbital angular momentum adjuster in response to the detection signal and/or controlling the propagation direction adjuster in response to the detection signal.
  • the advantage of such a control unit may be that it enables looking for the optimal characteristics of the first light beam with respect to the efficiency of the second light beam generating process. This process may be executed automatically when the control unit comprises a computer or manually, when a human acts as control unit.
  • control unit is arranged for adjusting in response to the detection signal: the orbital angular momentum of the first light beam to the pitch of the helical structure of the sample; and/or the handedness of the first light beam to the handedness or the opposite handedness of the helical structure of the sample.
  • control unit is arranged for adjusting in response to the detection signal the mean propagation direction of the first light beam to the direction of the helix axis of the helical structure of the sample.
  • the detector is arranged for providing a detection signal
  • control unit is arranged to vary one of three characteristics of the first light beam, the three characteristics being: the pitch of its wave front, the handedness of its wave front, and the mean propagation direction, on the basis of the detection signal, by controlling the orbital angular momentum adjuster or by controlling the propagation direction adjuster.
  • control unit is arranged to receive said detection signal and to control the orbital angular momentum adjuster and/or by controlling the propagation direction adjuster in response to the detection signal, such that detection signal achieves a predetermined criterion.
  • said predetermined criterion corresponds to a maximum light intensity of the detected second light beam.
  • control unit is arranged to determine a matching value for said one characteristic, wherein the matching value is a value of said one characteristic at which the detection signal achieves said predetermined criterion.
  • the control unit may vary one of three characteristics of the first light beam (i.e. the pitch or the handedness of its wave front or the mean propagation direction of the first light beam) by controlling the orbital angular momentum adjuster and/or by controlling the propagation direction adjuster. On the basis of the detection signals during the variation of this one characteristic, the control unit may determine that the detection signal has achieved a predetermined criterion, for example that a maximum intensity of light is detected at a certain value for said characteristic.
  • said characteristic of the first light beam matches the corresponding characteristic of the sample (i.e. the pitch of wave front of the first light beam corresponds to the pitch of the helical structure of the sample, the handedness of the wave front of the first light beam corresponds to the handedness or the opposite of the handedness of the helical structure of the sample or the mean propagation direction of the first light beam corresponds to the direction of the helix axis of the helical structure of the sample).
  • the detector will detect a maximum light intensity (as is explained below). As a consequence, information about the characteristics of the helical structure of the sample is obtained, because the characteristics of the helical structure of the sample may follow from the matching values.
  • the intensity of the light detected on the detector will be lower than in the case that the characteristics of the first light beam match the characteristics of the helical structure of the sample.
  • the matching value of a characteristic of the first light beam provides information about the sample, i.e. about the value of the corresponding characteristic of helical structure of the sample.
  • the detector comprising one of more filters for selectively detecting a part of the second light beam, wherein the part of the second light beam comprises an orbital angular momentum within a predefined orbital angular momentum range and/or wavelength within a predefined wavelength range.
  • the predefined orbital angular momentum range may be in the range of 1 -100 per photon and/or the predefined wavelength range in the range of 700 - 1000 nm.
  • the advantage of such a detector may be that it prevents spurious light to be detected that, for example, is generated by molecular structures or light generation processes that are not to be studied.
  • This light may have a different orbital angular momentum and/or wavelength than the light generated by the molecular structures or processes to be studied.
  • the light source may comprise, in another embodiment of the microscopy system according to the invention, a light generator for generating a light beam and a mode converter for filtering the light beam to generate a first light beam with an orbital angular momentum.
  • the sample comprises biological tissue, especially collagen. Details of the structure of collagen - as well as other biological tissue - might provide important information for research, therapy or diagnostic purposes. Up to now biological tissue having a molecular helical structure was difficult to examine.
  • one or more characteristics of the first light beam are adjusted in order to match one of more characteristics of the sample, comprising at least one of molecular helical structure.
  • the characteristics of the first light beam may comprise the orbital angular momentum of the first light beam, the handedness of the first light beam, and the mean propagation direction of the first light beam.
  • the characteristics of the sample may comprise the pitch of the helical structure, the handedness of the helical structure and the direction of a helix axis of the helical structure.
  • a use of a light beam exhibiting an orbital angular momentum is provided for performing microscopy on a sample comprising a at least one or a plurality of molecular helical structures.
  • the sample comprises biological tissue, especially biological tissue of a mammal like a human. Collagen can be examined very well with the microscopy system according to the invention and/or method according to the invention.
  • Figure 1 shows a helical structure
  • Figure 2 shows an embodiment of a microscopy system according to the invention
  • Figure 3 shows an embodiment of a microscopy system arranged to use a light beam exhibiting an orbital angular momentum light.
  • a helical structure has been depicted.
  • the helical structure may be characterized by its direction, indicated by arrow a and its pitch, indicated by distance b.
  • Helical structures have an orientation or handedness, indicated by arrow c and a helix is either left-handed or right-handed.
  • Figure 1 shows a right-handed helix.
  • the wave front of the electromagnetic radiation has a helical structure.
  • the orbital angular momentum is expressed in a multiple of per photon.
  • I the pitch is decreased proportionally.
  • a light beam can be scattered in a material both by linear scattering and by non-linear scattering.
  • the wavelength of the scattered light beam equals the wavelength of the excitation light beam.
  • the wavelength of the scattered light beam equals half the wavelength of the excitation light beam.
  • Other non-linear scattering processes may also occur, when an excitation light beam is scattered in a sample.
  • Light source 1 1 is arranged for generating a first light beam or excitation light beam which exhibits an orbital angular momentum.
  • Light source 1 1 may comprise a light generator 1 for generating a light beam and a mode converter 3 for filtering the light beam to generate a first light beam with an orbital angular moment.
  • the mode convertor may be a spiral phase plate, a (holographic) grating with a dislocation or a spatial phase modulator, for example a pixelated LCD screen with spatially variant phase. These types of mode convertors are well known in the art.
  • the light generator 1 may be a laser, for example an ultra-fast laser source with a pulse width of 100 fs or smaller and a wavelength in the range of 700-1000 nm.
  • the light source 1 1 may comprise a beam cleaning device 2 comprising lenses and/or pinholes in order to create a collimated first light beam with a beam waist adjusted to the entrance pupil of lens 6.
  • the optical assembly 15 for focusing the first light beam on the sample area 14 containing a sample 7 and for focusing a second light beam on the detector comprises lenses 4,5,6, 8 and 9. It also possible that a separate lens or a separate set of lenses is arranged to focus the first light beam on the sample and a different lens or a different set of lenses is arranged to focus the second light beam on the detector.
  • the optical assembly 15 may also comprise pinholes.
  • the microscopy system according to the invention may be a scanning microscopy system or a confocal microscopy system or a confocal scanning microscopy system.
  • the detector is a point detector and the optical assembly is arranged for focusing the second light beam on the point detector.
  • the microscopy system according to the invention may also be a second harmonic generation microscopy system.
  • the second harmonic light that is generated in the sample is used to study the sample.
  • the detector detects the light intensity of the second light beam that is focused on the detector.
  • the detector may provide a detection signal, being representative of the detected light intensity.
  • the sample area might be provided with a sample holder 12 holding the sample 7.
  • a dichroic mirror 4 is provided, which separates the excitation light from the second harmonic generated scattered light.
  • a scanning mirror 5 may be provided to scan the sample with the first light beam and to de-scan the second light beam.
  • Detector 10 may be a standard detector know in art of the scanning optical microscopy and may be provided with one of more filters for selectively detecting a part of the second light beam. In this manner only light will be detected which has an orbital angular momentum within a predefined orbital angular momentum range and/or a wavelength within a predefined wavelength range. This will decrease the detection of spurious light coming from other sources than the scattering process in the sample.
  • the filter for filtering out light having an orbital angular momentum outside a predefined range may comprise of the same elements as the mode converter.
  • the microscopy system may comprise an orbital angular momentum adjuster for adjusting the orbital angular momentum of the first light beam.
  • the orbital angular momentum of the first light beam or excitation light beam may be adjusted in various ways.
  • the mode converter may comprise an adjuster which acts on the working of the mode converter, for example on the working of the pixelated LCD screen with spatially variant phase. It also possible to provide an extra mode convertor in the light path of the first light beam.
  • the microscopy system may comprise a propagation direction adjuster for adjusting a mean propagation direction of the first light beam with respect to the sample area.
  • This adjuster can act on various elements of the microscopy system. It may, for example, change the direction of light which is sent out by the light source. It may also change the position of the lenses in the optical arrangement and/or the sample holder and thereby change the position of the sample with respect to the first light beam.
  • the microscopy system may comprise a control unit 13 that controls the orbital angular momentum adjuster in order to adjust the orbital angular momentum in response to a detection signal, and/or the propagation direction adjuster in order to adjust the mean propagation direction in response to the detection signal.
  • This control unit may be an integrated circuit or computer, programmed to execute this function. It may also be a human, who receives information about the detection of the second light beam from the detector, for example on a display, and then controls one or both adjusters. In Figure 2 the control unit 13 controls the light source 1 1 and the optical assembly 15.
  • control unit 13 may also control the sample holder 12 and/or mode convertor 3.
  • the microscopy system may comprise a sample with one or more helical structures, for example collagen molecules, but also other materials, for example biological tissue or tissue found in mammals, may be used.
  • the scattering process in the microscopy system will be more efficient when the characteristics of the first light beam or excitation light beam more or less match the characteristics of the molecular structures in the sample.
  • the characteristics of the sample may comprise the pitch of the helical structure, the handedness of the helical structure and the direction of a helix axis of the helical structure. By changing the orbital angular momentum of the first light beam, the pitch and the handedness of its wave front may be adjusted in order to match these characteristics of the sample.
  • propagation direction of the first light beam may also be adjusted to match the direction of the helix axis of the helical structure of the sample. The more these characteristics are matched, the more efficient the scattering process will take place and the more light will be detected by the detector.
  • the detector is a point detector and the second light beam will be focussed on the point detector .
  • the detector detects a higher light intensity of the second light beam if the second light beam comprises more light that does not possess an orbital angular momentum. It appears that light that possesses an orbital angular momentum can not be focussed on a point detector.
  • the second light beam may comprise light that does not possess an orbital angular momentum. In that case, a maximum light intensity may be detected by the detector.
  • the second light beam When the microscopy system is a second harmonic generation microscopy system, the second light beam will normally not be focussed on a point detector. Therefore, light may be detected by the detector irrespective of its orbital angular momentum. Generation of the second harmonic light in the sample will be most efficient when the handedness of the wave front of the first light beam corresponds to the handedness of the helical structure of the sample. In that case, a maximum of light intensity of the second light beam may be detected.
  • a maximum light intensity may be detected when the handedness of the wave front of the first light beam corresponds to the opposite of the handedness of the helical structure of the sample.
  • a maximum light intensity may be detected when the handedness of the wave front of the first light beam corresponds to the handedness of the helical structure of the sample.
  • handedness of the wave front of the first light beam corresponds to the handedness of the helical structure of the sample.
  • the detected light intensity may be less than when the characteristics of the first light beam do completely match the characteristics of the helical structure of the sample. This effect may be used to study the characteristics of the helical structure of the sample.
  • the control unit may vary one of three characteristics of the first light beam (i.e. the pitch or the handedness of its wave front or the mean propagation direction of the first light beam) by controlling the orbital angular momentum adjuster or by controlling the propagation direction adjuster. In the meantime, the other two characteristics of the first light beam may be kept constant. On the basis of the detection signal during the variation of this
  • control unit may determine that the detection signal achieves a
  • predetermined criterion for example that a maximum intensity of light is detected at a certain value for said characteristic.
  • said characteristic of the first light beam matches the corresponding characteristic of the sample (i.e. the pitch of wave front of the first light beam corresponds to the pitch of the helical structure of the sample, the handedness of the wave front of the first light beam corresponds to the handedness or the opposite of the handedness of the helical structure of the sample, or the mean propagation direction of the first light beam corresponds to the direction of the helix axis of the helical structure of the sample).
  • the matching values provide information about the sample, i.e. about the value of the corresponding characteristics of helix structure of the sample.
  • the varying of one of three characteristics may be achieved by controlling the orbital momentum adjuster and/or the propagation direction adjuster such that said one
  • characteristic of the first light beam successively has a value from a predetermined range.
  • the detection signal associated with each of these values may be stored by the control unit and the control unit may be arranged to select the value (referred to as matching value) at which the light intensity to which the detection signal is representative of, achieves the predetermined criterion, for example: the light intensity of the second light beam is at its maximum (this may be case when the detection signal is also at its maximum). In this way the control unit may determine a matching value for a characteristic.
  • the control unit may then proceed to vary another of the three characteristics of the first beam, while one or more of the previous varied characteristics may be held at their respective matching value.
  • the process of finding the set of matching values for one or more characteristics may be performed in different ways with different iteration steps.
  • the process may be optimized in the relation to the sample to be studied, i.e. the process may start with the values that are expected to match the characteristics of the sample.
  • the one or more matching values provide information about the helical structure of the sample, with respect to the pitch and the handedness of helical structure of the sample and the direction of the helix axis of the helical structure of the sample.
  • the pitch of the wave front of the first light beam will correspond to the pitch of the helical structure of the sample
  • the handedness (in the case of second generation microscopy) or the opposite of the handedness (in case of confocal (scanning) microscopy) of the wave front of the first light beam will correspond to the handedness of the helical structure of the sample and/or the mean propagation direction of the first light beam will correspond to the direction of the helix axis of the helical structure of the sample.
  • microscopy system enables the study of the
  • the intensity of the second light beam may decrease or increase when collagen in the sample changes its structure.
  • the microscopy system may have the dimension for being placed inside a hand held scanner or inside a
  • Figure 3 shows an embodiment of a microscopy system according to another aspect of the invention, which is not within the scope of claims as originally filed.
  • This microscopy system is arranged to use a light beam exhibiting an orbital angular momentum light.
  • the first light beam does not exhibit an orbital angular momentum but the second light beam does.
  • Mode converter 3 is placed in the light path of the second light beam or scattered light beam and in front of the detector.
  • the mode converter may act as a filter for the detector i.e. as an orbital angular momentum filter, enabling a selective detection of a part of the second light beam.
  • Further embodiments of this embodiment may comprise the features of the microscopy system described above.
  • the microscopy system may be a confocal (scanning) microscopy system or a second harmonic generation microscopy system, as is explained above.
  • the light intensity detected by the detector depends on whether and/or to what extend the characteristics of the orbital angular momentum filter match the characteristics of the helical structure of the sample.
  • the characteristics of the orbital angular momentum filter may refer to change in orbital angular momentum of a light beam that passes through the orbital angular momentum filter or to the characteristics of the light (with respect to its orbital angular momentum) that will orbital angular momentum filter filters out.
  • the microscopy system may comprise an orbital angular momentum adjuster for adjusting the orbital angular momentum filter and thus for adjusting the characteristics of the orbital angular momentum filter.
  • the characteristics of the orbital angular momentum filter may be adjusted by a control unit which is controlling the orbital angular momentum adjuster.
  • the control unit may vary one or more characteristics of the orbital angular momentum filter and determine the matching values of said one or more characteristics.
  • One or more matching values provide information about the helical structure of the sample, for example with respect to the pitch and the handedness of the sample.
  • the sample can be examined in vivo as well.
  • in vitro examination one may place the sample in a sample holder arranged in the sample area.
  • in vivo examination one will, in general, not place the sample in a sample holder, but arrange the microscopic system such that the first light beam impinges upon the sample - which is here a part of the patient - to be examined.
  • Microscopy system comprising:
  • a light source for generating a first light beam
  • a sample area for accommodating a sample to be examined
  • a detector for detecting a second light beam generated by the sample in response to the first light beam
  • an optical assembly for focusing the first light beam on the sample area and for focusing the second light beam on the detector
  • the light source is arranged for generating the first light beam with an orbital angular momentum.
  • Microscopy system according to clause 1 , further comprising a said sample to be examined, the sample comprising one or more molecular helical structures.
  • Microscopy system according to one of clauses 1 -3, wherein the detector is arranged for selectively detecting a wavelength of the second light beam, the wavelength of the second light beam being equal to half a wavelength of the first light beam or being equal to the wavelength of the first light beam.
  • the detector comprises electromagnetic radiation with wavelengths in the range of 700 - 1000 nm, and/or the detector is arranged for selectively detecting the second light beam comprising wavelengths in the range of 700 - 1000 nm and/or in the range of 350-500 nm.
  • Microscopy system according to one of clauses 1 -5, further comprising an orbital angular momentum adjuster for adjusting the orbital angular momentum of the first light beam, and/or a propagation direction adjuster for adjusting a mean propagation direction of the first light beam with respect to the sample area.
  • Microscopy system according to clause 6, wherein the detector is arranged for providing a detection signal in response to the detection of the second light beam - the detection signal preferably being representative for the second light beam -, the system further comprising a control unit arranged for:
  • - the handedness of the first light beam to - preferably to correspond essentially to - the handedness or the opposite of the handedness of the helical structure of the sample;
  • the mean propagation direction of the first light beam to - preferably to correspond essentially to - the direction of the helix axis of the helical structure of the sample.
  • Microscopy system according to one of clauses 1 -8, the detector comprising one of more filters for selectively detecting a part of the second light beam, wherein the part of the second light beam:
  • - comprises a wavelength within a predefined wavelength range.
  • Microscopy system according to one of clauses 1 -9, wherein the light source comprises: a light generator for generating a light beam;
  • a mode converter for filtering the light beam to generate the first light beam with an orbital angular moment.
  • Microscopy system according to one of the clauses 1 -1 1 , further comprising a sample holder arranged in the sample area.
  • Microscopy system according to one of the clauses 1 -12, wherein the microscopy system is a scanning microscopy system or a confocal scanning microscopy system
  • 12b Microscopy system according to one of clauses1 -12 and 12a, wherein the light source is a point source of light and the detector is a point detector and the optical assembly is arranged for focusing the first light beam on a point of the sample area (or the sample) and for focusing the second light beam from said point on the detector.
  • Method for performing microscopy comprising of steps a) generating a first light beam
  • the first light beam exhibits an orbital angular momentum.
  • Method for performing microscopy according to one of clauses 13-16, further comprising adjusting one or more characteristics of the first light beam, the characteristics of the first light beam comprising one or more of: the orbital angular momentum of the first light beam, the handedness or the opposite of the handedness of the first light beam; and the mean propagation direction of the first light beam.
  • the handedness of the first light beam to - preferably to correspond essentially to the handedness or the opposite of the handedness of the helical structure of the sample; and/or - the mean propagation direction of the first light beam to - preferably to correspond essentially to - the direction of the helix axis of the helical structure of the sample.
  • step d) comprises filtering and selectively detecting a part of the second light beam, wherein the part of the second light beam
  • - comprises a wavelength within a predefined wavelength range.
  • step f) Method for performing microscopy according to clause 24a or 24b wherein step f) further comprises keeping the other two characteristics of the first light beam constant.
  • the matching value of said one characteristic is a value at which the detector detects a maximum light intensity of the second light beam.
  • step f) comprises keeping one or more of the other two characteristics of the first light beam at their respective matching value.
  • Microscopy system comprising:
  • a light source for generating a first light beam
  • a detector for detecting a second light beam generated by the sample in response to the first light beam
  • an optical assembly for focusing the first light beam on the sample area and for focusing the second light beam on the detector, characterized in that
  • the detector comprises an orbital angular momentum filter for selectively detecting a part of the second light beam, wherein the part of the scattered light beam exhibits an orbital angular momentum within a predefined orbital angular momentum range, the predefined orbital angular momentum range preferably being 1 -100 h per photon.
  • Microscopy system according to clause 25 further comprising a sample comprising one or more molecular helical structures.
  • the sample is arranged for generating the second light beam by scattering of the first light beam.
  • Microscopy system according to one of clauses 25-27, wherein the detector is arranged for selectively detecting a wavelength of the second light beam, the wavelength of the second light beam being equal to half a wavelength of the first light beam or being equal to the wavelength of the first light beam.
  • Microscopy system according to one of clauses 25-28, wherein the first light beam comprises electromagnetic radiation with wavelengths in the range of 700 - 1000 nm; and/or the detector is arranged for selectively detecting the second light beam comprising wavelengths in the range of 700 - 1000 nm and/or in the range of 350-500 nm.
  • Microscopy system according to one of clauses 25-29, further comprising an orbital angular momentum adjuster for adjusting the orbital angular momentum filter, and/or a propagation direction adjuster for adjusting a mean propagation direction of the first light beam with respect to the sample area.
  • Microscopy system according to clause 30, wherein the detector is arranged for providing a detection signal in response to the detection of the second light beam - the detection signal preferably being representative for the second light beam -, the system further comprising a control unit arranged for:
  • Microscopy system according to one of clauses 25-31 , the detector comprising one or more filters for selectively detecting a part of the second light beam, wherein the part of the second light beam comprises a wavelength within a predefined wavelength range.
  • the sample comprises biological tissue, such as collagen.
  • Microscopy system according to one of the clauses 25 - 33, further comprising a sample holder arranged in the sample area. 36] Method for performing microscopy, comprising of steps
  • the part of the second light beam exhibits an orbital angular momentum within a predefined orbital angular momentum range, the predefined orbital angular momentum range preferably being 1 -100 per photon.
  • the orbital angular momentum filter and/or a mean propagation direction of the first light beam are adjusted in response to the detection of the second light beam.
  • step d) comprises filtering and selectively detecting a part of the second light beam, wherein the part of the second light beam comprises a wavelength within a predefined wavelength range.

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  • Physics & Mathematics (AREA)
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  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
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  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention porte sur un système de microscopie qui comprend une source lumineuse pour générer un premier faisceau lumineux, une zone d'échantillon pour recevoir un échantillon devant être examiné, un détecteur pour détecter un second faisceau lumineux généré par l'échantillon en réponse au premier faisceau lumineux et un ensemble optique pour focaliser le premier faisceau lumineux sur la zone d'échantillon et pour focaliser le second faisceau lumineux sur le détecteur. La source lumineuse est agencée pour générer le premier faisceau lumineux avec un moment angulaire orbital. Le système peut comprendre un échantillon avec une ou plusieurs structures hélicoïdales, par exemple des structures moléculaires de collagène. Le procédé de dispersion sera plus efficace lorsque les caractéristiques du premier faisceau lumineux correspondent aux caractéristiques des structures moléculaires dans l'échantillon. Par modification du moment angulaire orbital du premier faisceau lumineux, le pas et l'aptitude à la manipulation de son front d'onde peuvent être réglés afin de correspondre aux caractéristiques de l'échantillon.
PCT/NL2010/050547 2009-09-01 2010-09-01 Système et procédé pour réaliser une microscopie avec une lumière présentant un moment angulaire orbital Ceased WO2011028109A1 (fr)

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US11906722B2 (en) * 2017-02-17 2024-02-20 Osaka University Electromagnetic wave determining device, flow cytometer, electromagnetic wave determining method, and electromagnetic wave determining program
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US12339217B2 (en) 2020-04-01 2025-06-24 Thinkcyte K.K. Flow cytometer

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150260650A1 (en) * 2014-03-12 2015-09-17 Solyman Ashrafi System and method for making concentration measurements within a sample material using orbital angular momentum
US9267877B2 (en) * 2014-03-12 2016-02-23 Nxgen Partners Ip, Llc System and method for making concentration measurements within a sample material using orbital angular momentum
US20170322152A1 (en) * 2014-03-12 2017-11-09 Nxgen Partners Ip, Llc System and method for making concentration measurements within a sample material using orbital angular momentum
US10082463B2 (en) * 2014-03-12 2018-09-25 Nxgen Partners Ip, Llc System and method for making concentration measurements within a sample material using orbital angular momentum
US9500586B2 (en) 2014-07-24 2016-11-22 Nxgen Partners Ip, Llc System and method using OAM spectroscopy leveraging fractional orbital angular momentum as signature to detect materials
US11002677B2 (en) 2015-10-05 2021-05-11 Nxgen Partners Ip, Llc System and method for multi-parameter spectroscopy
US12230023B2 (en) 2015-10-28 2025-02-18 The University Of Tokyo Analysis device
US11906722B2 (en) * 2017-02-17 2024-02-20 Osaka University Electromagnetic wave determining device, flow cytometer, electromagnetic wave determining method, and electromagnetic wave determining program
US12259311B2 (en) 2018-06-13 2025-03-25 Thinkcyte K.K. Methods and systems for cytometry
US12235202B2 (en) 2019-12-27 2025-02-25 Thinkcyte K.K. Flow cytometer performance evaluation method and standard particle suspension
US12298221B2 (en) 2020-04-01 2025-05-13 Thinkcyte K.K. Observation device
US12339217B2 (en) 2020-04-01 2025-06-24 Thinkcyte K.K. Flow cytometer

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