WO2009022245A2 - Mechanical resonance detection system - Google Patents

Mechanical resonance detection system Download PDF

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Publication number
WO2009022245A2
WO2009022245A2 PCT/IB2008/052972 IB2008052972W WO2009022245A2 WO 2009022245 A2 WO2009022245 A2 WO 2009022245A2 IB 2008052972 W IB2008052972 W IB 2008052972W WO 2009022245 A2 WO2009022245 A2 WO 2009022245A2
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WO
WIPO (PCT)
Prior art keywords
mechanical vibration
sample holder
mechanical
vibration
lens
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Application number
PCT/IB2008/052972
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French (fr)
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WO2009022245A3 (en
Inventor
Dirk L. J. Vossen
Ruud Vlutters
Calina Ciuhu
Frederik J. De Bruijn
Original Assignee
Koninklijke Philips Electronics N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Koninklijke Philips Electronics N.V. filed Critical Koninklijke Philips Electronics N.V.
Publication of WO2009022245A2 publication Critical patent/WO2009022245A2/en
Publication of WO2009022245A3 publication Critical patent/WO2009022245A3/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01HMEASUREMENT OF MECHANICAL VIBRATIONS OR ULTRASONIC, SONIC OR INFRASONIC WAVES
    • G01H13/00Measuring resonant frequency

Definitions

  • An aspect of the invention relates to a mechanical resonance detection system for detecting a mechanical resonance of a physical object.
  • the physical object may be, for example, a biological sample.
  • the mechanical resonance may concern a natural frequency of an element in the physical object that constitutes a mass-spring- damper system.
  • Other aspects of the invention relate to a method of detecting a mechanical resonance, an optical imaging assembly, and a computer program product.
  • Mechanical resonance of a physical object can be detected in the following manner.
  • a mechanical vibration is applied to the physical object.
  • the mechanical vibration has a given frequency, which is referred to as vibration frequency hereinafter.
  • the physical object is exposed to a stroboscopic illumination, which is synchronized with the mechanical vibration.
  • An image of the physical object is captured during the stroboscopic illumination thereof.
  • the stroboscopic illumination prevents the image from being blurred due to the mechanical vibration, which the physical object undergoes.
  • the independent claims define various aspects of the invention.
  • the dependent claims define additional features for implementing the invention to advantage.
  • the invention takes the following points into consideration. Using stroboscopic illumination to form an image of an object requires a relatively long exposure time. This is because the object will receive less light energy over a given interval time compared with constant illumination. A detection process based on stroboscopic illumination may therefore be relatively slow, or may be relatively inaccurate, or both. What is more, providing a physical object with a reference mark, which is required for detection of relative motion, may be a delicate and cumbersome task. This is particularly true if the physical object is a biological sample.
  • a vibration applicator imposes a mechanical vibration at various different frequencies onto at least a portion of a physical object.
  • An imaging assembly captures images within an imaging frame that lies in at least a portion of the physical object, which undergoes the mechanical vibration. At least one element of the imaging assembly equally undergoes the mechanical vibration so that the imaging frame moves in synchronization with the mechanical vibration.
  • An analyzer analyzes the images so as to provide an indication of a frequency of the mechanical vibration whereby a relatively high degree of blur occurs in an image.
  • the physical object may be illuminated in a continuous fashion, while an image of the physical object is formed. There is no need for any stroboscopic illumination. Accordingly, relatively short exposure times may be used. What is more, the physical object need not be provided with a reference mark in order to determine of relative motion. This simplifies a detection process.
  • the images reveal a blur characteristic that provides information about mechanical properties of the physical object. More specifically, the frequency of the mechanical vibration whereby a relatively high degree of blur occurs indicates a mechanical resonance. For those reasons, the invention allows achieving a sufficiently accurate detection result in a cost-efficient manner.
  • An implementation of the invention advantageously comprises one or more of following additional features, which are described in separate paragraphs that correspond with individual dependent claims.
  • a sample holder for holding the physical object may be coupled to undergo the mechanical vibration.
  • the sample holder may be provided with a sample holder lens so that the sample holder lens moves in synchronization with the mechanical vibration.
  • the sample holder lens forms part of the imaging assembly, which may further comprise a capturing module with a capturing lens and an image sensor.
  • the sample holder preferably comprises a substrate having two main faces, one for holding the physical object, the other main face being provided with the sample holder lens.
  • Such a sample holder may have a relatively low mass, which allows relatively high vibration frequencies.
  • Another embodiment may comprise a laser for providing a laser beam.
  • a focusing lens causes the laser beam to have a focusing point in the physical object.
  • the focusing lens forms part of the imaging assembly, and undergoes the mechanical vibration so that the focusing point and the imaging frame in moves in synchronization with the mechanical vibration.
  • Such an embodiment which may comprise a so-called optical tweezer, equally allows relatively high vibration frequencies.
  • FIG.1 is a block diagram that illustrates a mechanical resonance detection system.
  • FIG.2 is a block diagram that illustrates a portion of a first alternative mechanical resonance detection system.
  • FIG.3 is a block diagram that illustrates a second alternative mechanical resonance detection system.
  • FIG.4 is a flow chart diagram that illustrates a series of steps, which are carried out in the mechanical resonance detection system.
  • FIG.l illustrates a mechanical resonance detection system DSYl for detecting a mechanical resonance of a physical object.
  • the physical object which will be referred to as sample S hereinafter, is placed in a sample holder SHL.
  • the sample S may be, for example, of a biological nature.
  • the mechanical resonance detection system DSYl further comprises the following functional entities: a variable frequency oscillator VFO, an electromechanical transducer EMT, a capturing module CPM, a blur analyzer BLA, a data analyzer DTA, and a controller CTRL.
  • the controller CTRL may be in the form of, for example, a suitably programmed processor.
  • the blur analyzer BLA, the data analyzer DTA may also be in the form of a suitably programmed processor.
  • a single processor may comprise the controller CTRL, the blur analyzer BLA, and the data analyzer DTA, as well as other functional entities.
  • the capturing module CPM comprises an image sensor SN and a capturing lens LC.
  • the sample holder SHL is provided with a sample holder lens LS.
  • the sample holder lens LS, the capturing lens LC, and the image sensor SN form an imaging assembly IAS.
  • the imaging assembly IAS is capable of projecting a particular area that lies, at least partially, within the sample S onto the image sensor SN while achieving correct focus. That is, the imaging assembly IAS defines an imaging frame that confines the particular area, which is projected onto the image sensor SN.
  • the imaging frame has a spatial location that can be adjusted by displacing the sample holder lens LS or the capturing lens LC, or both.
  • the image sensor SN can be regarded as a matrix of pixels. Each pixel corresponds with a particular point within the imaging frame. Such a point will be referred to as pixel point hereinafter. Consequently, the imaging frame can be regarded as a matrix of pixel points.
  • the mechanical resonance detection system DSYl may be provided with an illumination assembly for illuminating the sample S.
  • the illumination assembly may comprise, for example, a beam splitting cube that is arranged between the capturing lens LC and the sample holder lens LS.
  • the beam splitting cube receives a light beam from a light source, which may have a side location, and projects this light beam onto the sample S.
  • the sample holder SHL may be provided with a substrate that has a main face on which the sample is placed, and an opposite main face that is provided with a condenser lens. The sample S is illuminated via the condenser lens, which forms part of the illumination assembly in this example.
  • the mechanical resonance detection system DSYl basically operates as follows.
  • the controller CTRL applies a frequency control signal FC to the variable frequency oscillator VFO.
  • the variable frequency oscillator VFO provides an oscillation signal OS that has a frequency, which is determined by the frequency control signal FC.
  • the electromechanical transducer EMT effectively transforms the oscillation signal OS into a mechanical vibration MV of the same frequency. This frequency will be referred to hereinafter as vibration frequency.
  • the vibration frequency may be, for example, comprised in a range between 1 kilohertz (kHz) and 1O kHz.
  • the sample holder SHL is subjected to the mechanical vibration MV, which the electromechanical transducer EMT provides in response to the oscillation signal OS.
  • the sample holder SHL transfers the mechanical vibration MV to the sample S.
  • the sample holder lens LS which forms part of the sample holder SHL, equally undergoes the mechanical vibration MV.
  • the sample holder SHL may be constructed so that the sample holder lens LS maintains a fixed position with respect to the sample S.
  • the image sensor SN captures light radiation that emanates from within the imaging frame during an exposure time.
  • the exposure time preferably comprises several periods of the mechanical vibration MV.
  • the exposure time may be adjusted by means of, for example, the controller CTRL. Accordingly, the image sensor SN within the capturing module CPM provides an image IM, which represents a portion of the sample S that is within the imaging frame.
  • the imaging frame moves in synchronization with the mechanical vibration MV that is applied to the sample holder SHL. This is because the sample holder SHL transfers the mechanical vibration MV to the sample holder lens LS.
  • the imaging frame can be regarded as a matrix of pixel points. Each pixel point follows a trajectory back- and-forth with a frequency that corresponds to the vibration frequency. The trajectory depends on the respective optical properties of the sample holder lens LS and the capturing lens LC, the respective distances of these lenses with respect to the image sensor SN, and the mechanical vibration MV in terms of amplitude.
  • the image IM that the image sensor SN provides may be blurred to a certain extent due to motion of the imaging frame. That is, the image IM may comprise a certain degree of motion blur.
  • the image IM may be blurred in case the sample S comprises one or more elements that constitute a mass-spring-damper system. Such an element will be referred to as resonating element hereinafter. Each resonating element has a natural frequency. Let it be assumed that the exposure time comprises several periods of the mechanical vibration MV. Let it further be assumed that the sample S comprises a resonating element whose natural frequency is different from the vibration frequency.
  • the resonating element will exhibit a vibration that differs to a certain extent, in terms of phase and magnitude, from the mechanical vibration MV that the sample holder lens LS exhibits.
  • the resonating element may therefore have a somewhat blurry appearance in the image IM. This is because a point of the resonating element will be smeared out, as it were, over several pixels.
  • the vibration frequency is equal to the natural frequency of the resonating element concerned.
  • the resonating element is particularly sensitive to the mechanical vibration MV that is applied to the sample holder LS.
  • the resonating element will exhibit a vibration of relatively large magnitude, which may differ in phase from the mechanical vibration MV that the sample holder lens LS exhibits.
  • the resonating element will typically have a more blurry appearance in the image IM than in images captured at vibration frequencies that are substantially different from the natural frequency. That is, the closer the vibration frequency is to the natural frequency of the resonating element concerned, the blurrier the image will be. Accordingly, it is possible to detect a mechanical resonance on the basis of a blur versus frequency characteristic.
  • the blur analyzer BLA processes the image IM, which the image sensor
  • the blur characteristic BL may be in the form of a matrix of blur metrics, whereby a blur metric provides a measure of blur for a particular pixel position.
  • the blur analyzer BLA may operate in accordance with a technique described in the article "Low Cost Blur Estimator” by H. Hu and G. de Haan, published in the proceedings of the IEEE International Conference on Image IM Processing (ICIP), October 2006, pages 617-620. Another technique, which may be used, is described in the article "Local Scale Control for Edge Detection and Blur Estimation” by J.H. Elder and S. W. Zucker, published in IEEE Transactions on Pattern Analysis and Machine Intelligence, Vol.20, No.7, July 1998.
  • FIG.2 illustrates a portion of a first alternative system DS Y2, which comprises an alternative sample holder SHLA.
  • the first alternative system DSY2 may comprise further functional entities similar to those of the mechanical resonance detection system DSYl illustrated in FIG. 1. That is, the first alternative system DSY2 may be obtained by replacing the sample holder SHL illustrated in FIG.1 by the alternative sample holder SHLA illustrated in FIG. 2.
  • FIG.2 illustrates the alternative sample holder SHLA and the capturing module CPM, but not the other functional entities of the first alternative system DS Y2, for the sake of simplicity.
  • the alternative sample holder SHLA comprises a substrate SUB that has two main faces MFl, MF2.
  • the sample S is present on one of the two main faces MFl.
  • the other main face MF2 of the substrate SUB is provided with the sample holder lens LS.
  • the capturing module CPM faces the main face MF2 that is provided with the sample holder lens LS.
  • the sample holder lens LS, the capturing lens LC, and the image sensor SN constitute the imaging assembly IAS in a fashion similar to that in the mechanical resonance detection system DSYl illustrated in FIG.l.
  • the substrate SUB receives the mechanical vibration MV that the electromechanical transducer EMT provides and transfers this vibration to the sample S and the sample holder lens LS.
  • the alternative sample holder SHLA may be implemented, for example, as a disposable slide on which the sample S can be placed.
  • the sample holder lens LS is preferably a micro lens with a short focal distance, which allows the alternative sample holder SHLA to have a relatively low mass. The lower the mass of the alternative sample holder SHLA is, the higher the vibration frequency may be. This equally applies to the sample holder SHL illustrated in FIG.1.
  • FIG. 3 illustrates a second alternative system DSY3, which comprises an actuating-and-capturing module ACPM and other functional entities, which are to similar to those of the mechanical resonance detection system DSYl illustrated in FIG.l.
  • the first alternative system DSY2 is obtained by replacing the capturing module CPM illustrated in FIG. 1 by the actuating-and-capturing module ACPM illustrated in FIG.3.
  • the actuating-and-capturing module ACPM comprises a laser LA in addition to an image sensor SN and a focusing lens LF.
  • the focusing lens LF can be regarded as an equivalent of the capturing lens LC illustrated in FIG.l in the sense that the focusing lens LF forms part of an imaging assembly IAS.
  • the electromechanical transducer EMT is arranged so that the mechanical vibration MV is applied to the focusing lens LF.
  • the focusing lens LF is mounted so that this lens exhibits an oscillating movement in a lateral direction with respect to the image sensor SN and the sample holder lens LS, as illustrated in FIG.3.
  • the sample holder SHL can be stationary.
  • the laser LA provides a laser beam, which is focused via the focusing lens LF so that a focusing point occurs within the sample S. Accordingly, using specific parameter known by a skilled person in the art, a so-called optical tweezer can be obtained.
  • the laser beam exerts an attractive force onto microscopic dielectric objects in the vicinity of the focusing point. Since the focusing lens LF is subject to the mechanical vibration MV, the focusing point, as well as the attractive force associated therewith, will follow a particular trajectory back-and-forth with a frequency that is equal to the vibration frequency. A microscopic dielectric object will try to follow the focusing point as it were.
  • FIG.4 illustrates a series of steps ST1-ST7 that the mechanical resonance detection system DSYl illustrated in FIG.l carries out in order to provide an indication of a mechanical resonance frequency of the sample S.
  • the first alternative system DSY2 and the second alternative system DSY3 may also carry out the series of steps ST1-ST7 illustrated in FIG.4 for the same purpose.
  • the controller CTRL receives various parameters: a minimum frequency FMIN, a maximum frequency FMAX, and a frequency step size FSTEP. These parameters define a stepwise scan of a frequency band, which is comprised between the minimum frequency FMIN and the maximum frequency FMAX.
  • the controller CTRL may receive the aforementioned parameters from a user interface, via which a user may specify these parameters.
  • the controller CTRL may also receive the aforementioned parameters from a master controller, which forms part of a bigger system. To that end, the master controller may execute a system control program, which determines the parameters concerned.
  • the current frequency F corresponds with the vibration frequency mentioned hereinbefore with reference to FIGS.1-3.
  • the frequency control signal FC may be in the form of, for example, a numerical value.
  • the controller CTRL determines the numerical value that will cause the variable frequency oscillator VFO to produce the current frequency F.
  • the controller CTRL may determine the numerical value by means of, for example, an equation, which is stored in the controller CTRL.
  • the controller CTRL may also comprise a table, which specifies respective numerical values for respective frequencies.
  • step ST4 the mechanical resonance detection system DSYl operates as described hereinbefore with reference to FIG.l.
  • the blur analyzer BLA establishes the blur characteristic BL of the image IM that is captured while the mechanical vibration MV is being applied to the sample S and at least an element of the imaging assembly IAS, which element is the sample holder lens LS in FIG.l.
  • the vibration frequency is the current frequency F.
  • the data analyzer DTA receives the blur characteristic BL and the frequency indication FI, which indicates the current frequency F that applies to the blur characteristic BL (BL, FI ⁇ DTA).
  • the mechanical resonance detection system DSYl carries out steps ST3-ST5 anew.
  • the blur characteristic BL is established for a new frequency of the mechanical vibration MV.
  • the stepwise scan is completed.
  • the data analyzer DTA has received respective blur characteristics that apply to respective vibration frequencies within the frequency band of interest.
  • the data analyzer DTA may store this measurement data in the form of, for example, a table that specifies the respective blur characteristics for the respective vibration frequencies.
  • the measurement data contains information about mechanical properties of the sample S under investigation.
  • the data analyzer DTA analyzes the measurement data, which the mechanical resonance detection system DSYl has generated by cyclically carrying out steps ST3-ST5.
  • the data analyzer DTA analyzes the measurement data so as to provide an indication of a mechanical resonance frequency, which is typically a vibration frequency whereby an image has a relatively high degree of blur.
  • This vibration frequency will be referred to as blur peak frequency FR hereinafter.
  • the blur peak frequency FR indicates the natural frequency of one or more resonating elements within the sample S under investigation.
  • the data analyzer DTA may provide the blur peak frequency FR as basic output data.
  • the data analyzer DTA may also provide a graph that represents a blur versus frequency characteristic or statistical parameters, which relate to the measurement data, or both. These different types of output data reveal the mechanical properties of the sample S under investigation.
  • the data analyzer DTA may analyze the measurement data in various different manners for the purpose of determining a mechanical resonance frequency. For example, the data analyzer DTA may identify the image in which the resonating element has the blurriest appearance. The data analyzer may then determine the vibration frequency at which this image was captured. The data analyzer DTA may directly designate this vibration frequency as the blur peak frequency. Alternatively, the data analyzer DTA may establish a blur versus frequency characteristic on the basis of the measurement data. This process may involve, for example, extrapolation techniques. The data analyzer DTA may then determine one or more blur peak frequencies from the blur versus frequency characteristic.
  • the invention may be applied to advantage in any type of product or method that involves detecting a mechanical resonance.
  • the invention may be applied in a medical analysis apparatus, in particular the field of cell cytometry analysis.
  • the invention may equally be applied to advantage in an apparatus for testing a mechanical construction.
  • FIGS. 1 and 2 the sample holder lens LS is subjected to the mechanical vibration MV
  • FIG.3 the capturing lens LC is subjected to the mechanical vibration MV.
  • the sample holder lens LS may be subjected to the mechanical vibration MV instead of the focusing lens LF, which may be stationary.
  • an analyzer may measure a difference between an image that was captured at a particular vibration frequency and an image that was captured without any mechanical vibration.
  • the difference indicates a degree of blur at the particular vibration frequency concerned.
  • the difference indicates where blurs occurs in the image concerned: a relatively large difference will occur in a blurred area.
  • the analyzer may measure a difference between an image that was captured at a particular vibration frequency and an image that was captured at another particular vibration frequency. In that case, the difference indicates a change in the degree of blur at the particular vibration frequencies concerned.
  • the indication may be in the form of a numerical value that expresses the frequency concerned, or a set of numerical values, each expressing a blur peak frequency.
  • the indication may also be in the form of a spectrum that reveals a blur versus frequency characteristic. Such a spectrum can be regarded as a fingerprint of the sample concerned. Samples that have similar mechanical properties will have similar fingerprints.
  • the spectrum may be provided in the form of, for example, a graph or a table.
  • a mechanical vibration which is imposed on a sample, may have any given orientation in a three-dimensional space that may be represented by means of three axes: x, y, and z.
  • the mechanical vibration may be exerted along any of these three axes or any other arbitrary axis in the three-dimensional space.
  • the mechanical vibration may follow any arbitrary trajectory in the three-dimensional space.
  • the mechanical vibration may follow a circular or an elliptical trajectory.
  • FIGS.1-3 illustrate examples in which the imaging assembly IAS comprises two lenses.
  • An imaging assembly may comprise more than two lenses.
  • one or more additional lenses may be arranged in a light path that extends between the sample S and the image sensor SN.
  • one or more additional lenses which are similar to the sample holder lens LS, may be added to the alternative sample holder SHLA.
  • an array of micro lenses may be present on the main face MF2 of the substrate SUB that faces the capturing module CPM. Such an array of lenses allows parallel imaging, as well as imaging in a multiplexed fashion.
  • lens should be understood in a broad sense.
  • the term includes any entity that is capable of manipulating a light beam, in particular in terms of convergence and divergence.
  • the term lens includes a lens system, which comprises various elements. One or more of these elements may be, for example, diffractive elements,
  • elements may be, for example, diffractive elements.
  • the drawings are very diagrammatic, each representing only one possible embodiment of the invention. Thus, although a drawing shows different functions as different blocks, this by no means excludes that a single item of hardware or software carries out several functions. Nor does it exclude that an assembly of items of hardware or software or both carry out a function.

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Abstract

In a mechanical resonance detection system, a vibration applicator (VFO, EMT) imposes a mechanical vibration (MV) at various different frequencies onto at least a portion of a physical object (S). An imaging assembly (IAS) captures images (IM) within an imaging frame that lies in at least a portion of the physical object (S), which undergoes the mechanical vibration (MV). At least one element of the imaging assembly (IAS) equally undergoes the mechanical vibration (MV) so that the imaging frame moves in synchronization with the mechanical vibration (MV). An analyzer (BLA, DTA) analyzes the images so as to provide an indication of a frequencyofthe mechanical vibration whereby an image has a relatively high degree of blur.

Description

Mechanical resonance detection system.
FIELD OF THE INVENTION
An aspect of the invention relates to a mechanical resonance detection system for detecting a mechanical resonance of a physical object. The physical object may be, for example, a biological sample. The mechanical resonance may concern a natural frequency of an element in the physical object that constitutes a mass-spring- damper system. Other aspects of the invention relate to a method of detecting a mechanical resonance, an optical imaging assembly, and a computer program product.
BACKGROUND ART Mechanical resonance of a physical object can be detected in the following manner. A mechanical vibration is applied to the physical object. The mechanical vibration has a given frequency, which is referred to as vibration frequency hereinafter. The physical object is exposed to a stroboscopic illumination, which is synchronized with the mechanical vibration. An image of the physical object is captured during the stroboscopic illumination thereof. The stroboscopic illumination prevents the image from being blurred due to the mechanical vibration, which the physical object undergoes.
In order to determine a mechanical resonance, it is necessary to visualize relative motion, that is, motion of elements within the physical object relative to the mechanical vibration. To that end, the physical object needs to be provided with a reference mark.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a mechanical resonance detection system that can provide a sufficiently accurate result in a cost-efficient manner. The independent claims define various aspects of the invention. The dependent claims define additional features for implementing the invention to advantage. The invention takes the following points into consideration. Using stroboscopic illumination to form an image of an object requires a relatively long exposure time. This is because the object will receive less light energy over a given interval time compared with constant illumination. A detection process based on stroboscopic illumination may therefore be relatively slow, or may be relatively inaccurate, or both. What is more, providing a physical object with a reference mark, which is required for detection of relative motion, may be a delicate and cumbersome task. This is particularly true if the physical object is a biological sample.
In accordance with the invention, a vibration applicator imposes a mechanical vibration at various different frequencies onto at least a portion of a physical object. An imaging assembly captures images within an imaging frame that lies in at least a portion of the physical object, which undergoes the mechanical vibration. At least one element of the imaging assembly equally undergoes the mechanical vibration so that the imaging frame moves in synchronization with the mechanical vibration. An analyzer analyzes the images so as to provide an indication of a frequency of the mechanical vibration whereby a relatively high degree of blur occurs in an image.
The physical object may be illuminated in a continuous fashion, while an image of the physical object is formed. There is no need for any stroboscopic illumination. Accordingly, relatively short exposure times may be used. What is more, the physical object need not be provided with a reference mark in order to determine of relative motion. This simplifies a detection process. The images reveal a blur characteristic that provides information about mechanical properties of the physical object. More specifically, the frequency of the mechanical vibration whereby a relatively high degree of blur occurs indicates a mechanical resonance. For those reasons, the invention allows achieving a sufficiently accurate detection result in a cost-efficient manner.
An implementation of the invention advantageously comprises one or more of following additional features, which are described in separate paragraphs that correspond with individual dependent claims.
In an embodiment, a sample holder for holding the physical object may be coupled to undergo the mechanical vibration. The sample holder may be provided with a sample holder lens so that the sample holder lens moves in synchronization with the mechanical vibration. The sample holder lens forms part of the imaging assembly, which may further comprise a capturing module with a capturing lens and an image sensor. These features allow relatively high vibration frequencies. This is because the sample holder lens is the only element of the imaging assembly that needs to undergo the mechanical vibration. The sample holder lens will generally have a relatively low mass.
The sample holder preferably comprises a substrate having two main faces, one for holding the physical object, the other main face being provided with the sample holder lens. Such a sample holder may have a relatively low mass, which allows relatively high vibration frequencies.
Another embodiment may comprise a laser for providing a laser beam. A focusing lens causes the laser beam to have a focusing point in the physical object. The focusing lens forms part of the imaging assembly, and undergoes the mechanical vibration so that the focusing point and the imaging frame in moves in synchronization with the mechanical vibration. Such an embodiment, which may comprise a so-called optical tweezer, equally allows relatively high vibration frequencies.
A detailed description with reference to drawings illustrates the invention summarized hereinbefore, as well as the additional features.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG.1 is a block diagram that illustrates a mechanical resonance detection system.
FIG.2 is a block diagram that illustrates a portion of a first alternative mechanical resonance detection system. FIG.3 is a block diagram that illustrates a second alternative mechanical resonance detection system.
FIG.4 is a flow chart diagram that illustrates a series of steps, which are carried out in the mechanical resonance detection system.
DETAILED DESCRIPTION
FIG.l illustrates a mechanical resonance detection system DSYl for detecting a mechanical resonance of a physical object. The physical object, which will be referred to as sample S hereinafter, is placed in a sample holder SHL. The sample S may be, for example, of a biological nature. The mechanical resonance detection system DSYl further comprises the following functional entities: a variable frequency oscillator VFO, an electromechanical transducer EMT, a capturing module CPM, a blur analyzer BLA, a data analyzer DTA, and a controller CTRL. The controller CTRL may be in the form of, for example, a suitably programmed processor. The blur analyzer BLA, the data analyzer DTA may also be in the form of a suitably programmed processor. A single processor may comprise the controller CTRL, the blur analyzer BLA, and the data analyzer DTA, as well as other functional entities. In more detail, the capturing module CPM comprises an image sensor SN and a capturing lens LC. The sample holder SHL is provided with a sample holder lens LS. The sample holder lens LS, the capturing lens LC, and the image sensor SN form an imaging assembly IAS. The imaging assembly IAS is capable of projecting a particular area that lies, at least partially, within the sample S onto the image sensor SN while achieving correct focus. That is, the imaging assembly IAS defines an imaging frame that confines the particular area, which is projected onto the image sensor SN. The imaging frame has a spatial location that can be adjusted by displacing the sample holder lens LS or the capturing lens LC, or both. The image sensor SN can be regarded as a matrix of pixels. Each pixel corresponds with a particular point within the imaging frame. Such a point will be referred to as pixel point hereinafter. Consequently, the imaging frame can be regarded as a matrix of pixel points.
The mechanical resonance detection system DSYl may be provided with an illumination assembly for illuminating the sample S. The illumination assembly may comprise, for example, a beam splitting cube that is arranged between the capturing lens LC and the sample holder lens LS. The beam splitting cube receives a light beam from a light source, which may have a side location, and projects this light beam onto the sample S. As another example, the sample holder SHL may be provided with a substrate that has a main face on which the sample is placed, and an opposite main face that is provided with a condenser lens. The sample S is illuminated via the condenser lens, which forms part of the illumination assembly in this example. The mechanical resonance detection system DSYl basically operates as follows. The controller CTRL applies a frequency control signal FC to the variable frequency oscillator VFO. The variable frequency oscillator VFO provides an oscillation signal OS that has a frequency, which is determined by the frequency control signal FC. The electromechanical transducer EMT effectively transforms the oscillation signal OS into a mechanical vibration MV of the same frequency. This frequency will be referred to hereinafter as vibration frequency. The vibration frequency may be, for example, comprised in a range between 1 kilohertz (kHz) and 1O kHz.
The sample holder SHL is subjected to the mechanical vibration MV, which the electromechanical transducer EMT provides in response to the oscillation signal OS. The sample holder SHL transfers the mechanical vibration MV to the sample S. The sample holder lens LS, which forms part of the sample holder SHL, equally undergoes the mechanical vibration MV. The sample holder SHL may be constructed so that the sample holder lens LS maintains a fixed position with respect to the sample S.
The image sensor SN captures light radiation that emanates from within the imaging frame during an exposure time. The exposure time preferably comprises several periods of the mechanical vibration MV. The exposure time may be adjusted by means of, for example, the controller CTRL. Accordingly, the image sensor SN within the capturing module CPM provides an image IM, which represents a portion of the sample S that is within the imaging frame.
In terms of spatial location, the imaging frame moves in synchronization with the mechanical vibration MV that is applied to the sample holder SHL. This is because the sample holder SHL transfers the mechanical vibration MV to the sample holder lens LS. It has been explained hereinbefore that the imaging frame can be regarded as a matrix of pixel points. Each pixel point follows a trajectory back- and-forth with a frequency that corresponds to the vibration frequency. The trajectory depends on the respective optical properties of the sample holder lens LS and the capturing lens LC, the respective distances of these lenses with respect to the image sensor SN, and the mechanical vibration MV in terms of amplitude.
The image IM that the image sensor SN provides may be blurred to a certain extent due to motion of the imaging frame. That is, the image IM may comprise a certain degree of motion blur. The image IM may be blurred in case the sample S comprises one or more elements that constitute a mass-spring-damper system. Such an element will be referred to as resonating element hereinafter. Each resonating element has a natural frequency. Let it be assumed that the exposure time comprises several periods of the mechanical vibration MV. Let it further be assumed that the sample S comprises a resonating element whose natural frequency is different from the vibration frequency. In that case, the resonating element will exhibit a vibration that differs to a certain extent, in terms of phase and magnitude, from the mechanical vibration MV that the sample holder lens LS exhibits. The resonating element may therefore have a somewhat blurry appearance in the image IM. This is because a point of the resonating element will be smeared out, as it were, over several pixels.
Let it now be assumed that the vibration frequency is equal to the natural frequency of the resonating element concerned. In that case, the resonating element is particularly sensitive to the mechanical vibration MV that is applied to the sample holder LS. As a result, the resonating element will exhibit a vibration of relatively large magnitude, which may differ in phase from the mechanical vibration MV that the sample holder lens LS exhibits. The resonating element will typically have a more blurry appearance in the image IM than in images captured at vibration frequencies that are substantially different from the natural frequency. That is, the closer the vibration frequency is to the natural frequency of the resonating element concerned, the blurrier the image will be. Accordingly, it is possible to detect a mechanical resonance on the basis of a blur versus frequency characteristic. The blur analyzer BLA processes the image IM, which the image sensor
SN provides, so as to establish a blur characteristic BL of the image. The blur characteristic BL may be in the form of a matrix of blur metrics, whereby a blur metric provides a measure of blur for a particular pixel position. For example, the blur analyzer BLA may operate in accordance with a technique described in the article "Low Cost Blur Estimator" by H. Hu and G. de Haan, published in the proceedings of the IEEE International Conference on Image IM Processing (ICIP), October 2006, pages 617-620. Another technique, which may be used, is described in the article "Local Scale Control for Edge Detection and Blur Estimation" by J.H. Elder and S. W. Zucker, published in IEEE Transactions on Pattern Analysis and Machine Intelligence, Vol.20, No.7, July 1998.
The data analyzer DTA stores the blur characteristic BL in association with the vibration frequency that was applied when the image IM was taken. To that end, the data analyzer DTA receives a frequency indication FI from the controller CTRL, which informs the data analyzer DTA of the vibration frequency that was applied. Accordingly, the data analyzer DTA may constitute a table that specifies respective blur characteristics for respective vibration frequencies. This will be explained in greater detail hereinafter. FIG.2 illustrates a portion of a first alternative system DS Y2, which comprises an alternative sample holder SHLA. The first alternative system DSY2 may comprise further functional entities similar to those of the mechanical resonance detection system DSYl illustrated in FIG. 1. That is, the first alternative system DSY2 may be obtained by replacing the sample holder SHL illustrated in FIG.1 by the alternative sample holder SHLA illustrated in FIG. 2. The first alternative system
DSY2 may then comprise a capturing module CPM similar to that illustrated in FIG.l, which is provided with a capturing lens LC and an image sensor SN. FIG.2 illustrates the alternative sample holder SHLA and the capturing module CPM, but not the other functional entities of the first alternative system DS Y2, for the sake of simplicity. The alternative sample holder SHLA comprises a substrate SUB that has two main faces MFl, MF2. The sample S is present on one of the two main faces MFl. The other main face MF2 of the substrate SUB is provided with the sample holder lens LS. The capturing module CPM faces the main face MF2 that is provided with the sample holder lens LS. The sample holder lens LS, the capturing lens LC, and the image sensor SN constitute the imaging assembly IAS in a fashion similar to that in the mechanical resonance detection system DSYl illustrated in FIG.l. The substrate SUB receives the mechanical vibration MV that the electromechanical transducer EMT provides and transfers this vibration to the sample S and the sample holder lens LS. The alternative sample holder SHLA may be implemented, for example, as a disposable slide on which the sample S can be placed. The sample holder lens LS is preferably a micro lens with a short focal distance, which allows the alternative sample holder SHLA to have a relatively low mass. The lower the mass of the alternative sample holder SHLA is, the higher the vibration frequency may be. This equally applies to the sample holder SHL illustrated in FIG.1.
FIG. 3 illustrates a second alternative system DSY3, which comprises an actuating-and-capturing module ACPM and other functional entities, which are to similar to those of the mechanical resonance detection system DSYl illustrated in FIG.l. The first alternative system DSY2 is obtained by replacing the capturing module CPM illustrated in FIG. 1 by the actuating-and-capturing module ACPM illustrated in FIG.3.
The actuating-and-capturing module ACPM comprises a laser LA in addition to an image sensor SN and a focusing lens LF. The focusing lens LF can be regarded as an equivalent of the capturing lens LC illustrated in FIG.l in the sense that the focusing lens LF forms part of an imaging assembly IAS. The electromechanical transducer EMT is arranged so that the mechanical vibration MV is applied to the focusing lens LF. The focusing lens LF is mounted so that this lens exhibits an oscillating movement in a lateral direction with respect to the image sensor SN and the sample holder lens LS, as illustrated in FIG.3. The sample holder SHL can be stationary.
The laser LA provides a laser beam, which is focused via the focusing lens LF so that a focusing point occurs within the sample S. Accordingly, using specific parameter known by a skilled person in the art, a so-called optical tweezer can be obtained. The laser beam exerts an attractive force onto microscopic dielectric objects in the vicinity of the focusing point. Since the focusing lens LF is subject to the mechanical vibration MV, the focusing point, as well as the attractive force associated therewith, will follow a particular trajectory back-and-forth with a frequency that is equal to the vibration frequency. A microscopic dielectric object will try to follow the focusing point as it were.
Let it be assumed that the microscopic dielectric object, which tries to follow the focusing point of the laser beam, constitutes a mass-spring-damper system, which has a natural frequency as described hereinbefore. Let it further be assumed that the natural frequency is equal to the vibration frequency, or relatively close thereto. In that case, the microscopic dielectric object will have a relatively blurry appearance in the image IM that the image sensor SN provides. That is, the microscopic dielectric object will appear blurrier than in images captured at vibration frequencies that are substantially different from the natural frequency. FIG.4 illustrates a series of steps ST1-ST7 that the mechanical resonance detection system DSYl illustrated in FIG.l carries out in order to provide an indication of a mechanical resonance frequency of the sample S. The first alternative system DSY2 and the second alternative system DSY3 may also carry out the series of steps ST1-ST7 illustrated in FIG.4 for the same purpose.
In step STl, the controller CTRL receives various parameters: a minimum frequency FMIN, a maximum frequency FMAX, and a frequency step size FSTEP. These parameters define a stepwise scan of a frequency band, which is comprised between the minimum frequency FMIN and the maximum frequency FMAX. The controller CTRL may receive the aforementioned parameters from a user interface, via which a user may specify these parameters. The controller CTRL may also receive the aforementioned parameters from a master controller, which forms part of a bigger system. To that end, the master controller may execute a system control program, which determines the parameters concerned.
In step ST2, the controller CTRL defines a current frequency F, which is initially set to be the minimum frequency FMIN (F=FMIN). The current frequency F corresponds with the vibration frequency mentioned hereinbefore with reference to FIGS.1-3.
In step ST3, the controller CTRL establishes the frequency control signal FC so that the oscillation signal OS illustrated in FIG.l has the current frequency F (CTRL: FC => OS@F). The frequency control signal FC may be in the form of, for example, a numerical value. In that case, the controller CTRL determines the numerical value that will cause the variable frequency oscillator VFO to produce the current frequency F. The controller CTRL may determine the numerical value by means of, for example, an equation, which is stored in the controller CTRL. The controller CTRL may also comprise a table, which specifies respective numerical values for respective frequencies. In step ST4, the mechanical resonance detection system DSYl operates as described hereinbefore with reference to FIG.l. That is, the blur analyzer BLA establishes the blur characteristic BL of the image IM that is captured while the mechanical vibration MV is being applied to the sample S and at least an element of the imaging assembly IAS, which element is the sample holder lens LS in FIG.l. As mentioned hereinbefore, the vibration frequency is the current frequency F. The data analyzer DTA receives the blur characteristic BL and the frequency indication FI, which indicates the current frequency F that applies to the blur characteristic BL (BL, FI→DTA). In step ST5, the controller CTRL checks whether the current frequency F is equal to the maximum frequency FMAX, or not (F=FMAX?). In case the current frequency F is not equal to the maximum frequency FMAX, the frequency band of interest has not been completely scanned yet. In that case, the controller CTRL increments the current frequency F by the frequency step size FSTEP, which is done in step ST6 (F=F+FSTEP). Subsequently, the mechanical resonance detection system DSYl carries out steps ST3-ST5 anew. The blur characteristic BL is established for a new frequency of the mechanical vibration MV.
In case the controller CTRL establishes in step ST5 that the current frequency F is equal to the maximum frequency FMAX, the stepwise scan is completed. The data analyzer DTA has received respective blur characteristics that apply to respective vibration frequencies within the frequency band of interest. The data analyzer DTA may store this measurement data in the form of, for example, a table that specifies the respective blur characteristics for the respective vibration frequencies. The measurement data contains information about mechanical properties of the sample S under investigation.
In step ST7, the data analyzer DTA analyzes the measurement data, which the mechanical resonance detection system DSYl has generated by cyclically carrying out steps ST3-ST5. The data analyzer DTA analyzes the measurement data so as to provide an indication of a mechanical resonance frequency, which is typically a vibration frequency whereby an image has a relatively high degree of blur. This vibration frequency will be referred to as blur peak frequency FR hereinafter. The blur peak frequency FR indicates the natural frequency of one or more resonating elements within the sample S under investigation. The data analyzer DTA may provide the blur peak frequency FR as basic output data. The data analyzer DTA may also provide a graph that represents a blur versus frequency characteristic or statistical parameters, which relate to the measurement data, or both. These different types of output data reveal the mechanical properties of the sample S under investigation.
The data analyzer DTA may analyze the measurement data in various different manners for the purpose of determining a mechanical resonance frequency. For example, the data analyzer DTA may identify the image in which the resonating element has the blurriest appearance. The data analyzer may then determine the vibration frequency at which this image was captured. The data analyzer DTA may directly designate this vibration frequency as the blur peak frequency. Alternatively, the data analyzer DTA may establish a blur versus frequency characteristic on the basis of the measurement data. This process may involve, for example, extrapolation techniques. The data analyzer DTA may then determine one or more blur peak frequencies from the blur versus frequency characteristic.
CONCLUDING REMARKS
The detailed description hereinbefore with reference to the drawings is merely an illustration of the invention and the additional features, which are defined in the claims. The invention can be implemented in numerous different manners. In order to illustrate this, some alternatives are briefly indicated.
The invention may be applied to advantage in any type of product or method that involves detecting a mechanical resonance. For example, the invention may be applied in a medical analysis apparatus, in particular the field of cell cytometry analysis. The invention may equally be applied to advantage in an apparatus for testing a mechanical construction.
There are numerous different manners in which a mechanical resonance detection system in accordance with the invention can be implemented. The detailed description with reference to drawings provides a few examples in which only a part of an imaging assembly is subjected to mechanical vibration. In FIGS. 1 and 2, the sample holder lens LS is subjected to the mechanical vibration MV, whereas in FIG.3 the capturing lens LC is subjected to the mechanical vibration MV. It is also possible to apply a mechanical vibration to an imaging assembly in its entirety. Referring to FIG.3, the sample holder lens LS may be subjected to the mechanical vibration MV instead of the focusing lens LF, which may be stationary.
There are numerous different manners of analyzing images captured at various different vibration frequencies for the purpose of detecting a mechanical resonance. For example, an analyzer may measure a difference between an image that was captured at a particular vibration frequency and an image that was captured without any mechanical vibration. The difference indicates a degree of blur at the particular vibration frequency concerned. Moreover, the difference indicates where blurs occurs in the image concerned: a relatively large difference will occur in a blurred area. Alternatively, the analyzer may measure a difference between an image that was captured at a particular vibration frequency and an image that was captured at another particular vibration frequency. In that case, the difference indicates a change in the degree of blur at the particular vibration frequencies concerned.
There are numerous different fashions of providing an indication of a frequency of the mechanical vibration whereby an image has a relatively high degree of blur. The indication may be in the form of a numerical value that expresses the frequency concerned, or a set of numerical values, each expressing a blur peak frequency. The indication may also be in the form of a spectrum that reveals a blur versus frequency characteristic. Such a spectrum can be regarded as a fingerprint of the sample concerned. Samples that have similar mechanical properties will have similar fingerprints. The spectrum may be provided in the form of, for example, a graph or a table.
A mechanical vibration, which is imposed on a sample, may have any given orientation in a three-dimensional space that may be represented by means of three axes: x, y, and z. The mechanical vibration may be exerted along any of these three axes or any other arbitrary axis in the three-dimensional space. The mechanical vibration may follow any arbitrary trajectory in the three-dimensional space. For example, the mechanical vibration may follow a circular or an elliptical trajectory. There are numerous different manners in which an imaging assembly can be implemented. FIGS.1-3 illustrate examples in which the imaging assembly IAS comprises two lenses. An imaging assembly may comprise more than two lenses. For example, referring to FIG.l, one or more additional lenses may be arranged in a light path that extends between the sample S and the image sensor SN. As another example, referring to FIG.2, one or more additional lenses, which are similar to the sample holder lens LS, may be added to the alternative sample holder SHLA. Accordingly, an array of micro lenses may be present on the main face MF2 of the substrate SUB that faces the capturing module CPM. Such an array of lenses allows parallel imaging, as well as imaging in a multiplexed fashion.
The term "lens" should be understood in a broad sense. The term includes any entity that is capable of manipulating a light beam, in particular in terms of convergence and divergence. The term lens includes a lens system, which comprises various elements. One or more of these elements may be, for example, diffractive elements, There are numerous ways of implementing functions by means of items of hardware or software, or both. In this respect, the drawings are very diagrammatic, each representing only one possible embodiment of the invention. Thus, although a drawing shows different functions as different blocks, this by no means excludes that a single item of hardware or software carries out several functions. Nor does it exclude that an assembly of items of hardware or software or both carry out a function.
The remarks made herein before demonstrate that the detailed description with reference to the drawings, illustrate rather than limit the invention. There are numerous alternatives, which fall within the scope of the appended claims. Any reference sign in a claim should not be construed as limiting the claim. The word "comprising" does not exclude the presence of other elements or steps than those listed in a claim. The word "a" or "an" preceding an element or step ST does not exclude the presence of a plurality of such elements or steps.

Claims

CLAIMS:
1. A mechanical resonance detection system (DSYl, DSY2, DSY3) comprising: a vibration applicator (VFO, EMT) for imposing a mechanical vibration (MV) at various different frequencies onto at least a portion of a physical object (S); - an imaging assembly (IAS) for capturing images (IM) within an imaging frame that lies in at least a portion of the physical object (S), which undergoes the mechanical vibration (MV), at least one element of the imaging assembly (IAS) being coupled to equally undergo the mechanical vibration (MV) so that the imaging frame moves in synchronization with the mechanical vibration (MV); and an analyzer (BLA, DTA) for analyzing the images so as to provide an indication of a frequency of the mechanical vibration whereby an image has a relatively high degree of blur.
2. A mechanical resonance detection system as claimed in claim 1, comprising: a sample holder (SHL) for holding the physical object (S), the sample holder (SHL) being coupled to undergo the mechanical vibration (MV), the sample holder (SHL) being provided with a sample holder lens (LS) so that the sample holder lens (LS) moves in synchronization with the mechanical vibration (MV); and a capturing module (CPM) comprising a capturing lens (LC) and an image sensor (SN), the capturing module (CPM) and the sample holder lens (LS) forming the imaging assembly (IAS).
3. A mechanical resonance detection system as claimed in claim 2, the sample holder (SHL) comprising a substrate (SUB) having two main faces (MFl, MF2), one (MFl) for holding the physical object (S), the other main face (MF2) being provided with the sample holder lens (LS).
4. A mechanical resonance detection system as claimed in claim 1, comprising: a laser (LA) for providing a laser beam; and - a focusing lens (LF) for causing the laser beam to have a focusing point in the physical object (S), the focusing lens (LF) forming part of the imaging assembly (IAS) and being coupled to undergo the mechanical vibration (MV) so that the focusing point and the imaging frame in moves in synchronization with the mechanical vibration (MV).
5. A method of detecting a mechanical resonance comprising: a vibration application step in which a mechanical vibration (MV) is imposed at various different frequencies onto at least a portion of a physical object
(S); - an imaging step in which images (IM) are captured within an imaging frame that lies in at least a portion of the physical object (S), which undergoes the mechanical vibration (MV), the image (IM) being captured by means of an imaging assembly (IAS) of which at least one element undergoes the mechanical vibration (MV) so that the imaging frame moves in synchronization with the mechanical vibration (MV); and an analysis step in which the images (IM) are analyzed so as to provide an indication of a frequency of the mechanical vibration whereby an image has a relatively high degree of blur.
6. A computer program product for a programmable processor, the computer program product comprising a set of instructions that, when loaded into the programmable processor, causes the programmable processor to carry out the method according to claim 5.
7. An optical imaging assembly for a mechanical resonance detection system as claimed in claim 1 , comprising a sample holder (SHL) and a capturing module (CPM) as claimed in claim 2.
PCT/IB2008/052972 2007-08-10 2008-07-24 Mechanical resonance detection system WO2009022245A2 (en)

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