JP2004325223A - Measuring apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To quantitatively measure the viscoelastic force of a biological tissue smaller than the order of centimeters. <P>SOLUTION: A measuring apparatus is provided with a vessel 10 for storing the biological tissue O and a minute particle P, a laser output apparatus 1 for outputting a laser light for capturing the minute particle P, an operation part 9 for accepting an operation command from a measuring person, a deflection apparatus 5 for deflecting the laser light in response to the operation command, a focus lens 2 for focusing the laser light at a focus location CP, a detector 8 for detecting the displacement quantity of the minute particle P from the biological tissue O generated when the minute particle P captured by the laser light is applied to the biological tissue O and a viscous and elastic force calculation part 313 for calculating the viscous and elastic force of the anatomy O based on the displacement quantity. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a technique for examining a viscoelastic force of a living tissue such as a cell.
[0002]
[Prior art]
It is known that the hardness of a living tissue such as a cell differs depending on its type. Therefore, if the quantitative hardness of a living tissue can be measured and the cell type (for example, cancer cell) can be specified based on the measured hardness, a patient's disease can be specified.
[0003]
2. Description of the Related Art Conventionally, a magnetic resonance elasticity measurement method (Magnetic Resonance Elastography) has been known as a method for measuring a quantitative hardness of a living tissue such as a cell (Non-Patent Document 1). In this method, a lateral vibration is applied to the surface of a tissue, a cross-sectional image of a living tissue is acquired using an MRI (magnetic resonance imaging device), and the speed at which the vibration propagates through the tissue is measured by MRI. The calculation is based on the obtained cross-sectional image, and the hardness of the tissue is calculated based on the calculated speed. According to this method, the hardness of the living tissue can be measured non-invasively, and the distribution of the hardness (rigidity) in the tissue can be measured.
[0004]
[Non-patent document 1]
MR elastography Tetsuya Matsuda Mikio Suga Nikkei Medical Journal, Vol. 20, No. 6 (2000), pp. 291-300
[0005]
[Problems to be solved by the invention]
However, in the above method, it is difficult for MRI to obtain a cross-sectional image of a substance having a size of several centimeters or less. It was impossible to do.
[0006]
The present invention has been made to solve the above-described problems, and has as its object to provide a measuring device capable of quantitatively measuring a viscoelastic force of a living tissue smaller than several cm.
[0007]
[Means for Solving the Problems]
A measuring device according to the present invention is a measuring device that measures a viscoelastic force of a living tissue, a storing unit that stores the living tissue and the fine particles, and a laser output unit that outputs a laser beam for capturing the fine particles. Operating means for receiving an operation command from a measurer, and in response to the operation command received by the operating means, to move the fine particles captured by the laser light output by the laser output means, the laser light Deflecting means for deflecting, and a condensing means for guiding the laser light deflected by the deflecting means to the storage means, and for condensing the laser light in the storage means to cause the laser light to capture the fine particles, Detecting means for detecting an amount of displacement of the fine particles with respect to the laser light caused by pressing the fine particles against the living tissue; Based on the deviation amount, characterized by comprising a calculating means for calculating the viscoelastic forces of the living tissue.
[0008]
According to this configuration, the laser light is guided to the storage means so as to be condensed by the storage means, captures the fine particles at the light collection position, and presses the captured fine particles against the living tissue stored in the storage means. The amount of displacement of the fine particles generated when the particles are applied to the laser beam is detected, and a predetermined calculation is performed on the detected amount of displacement to measure the viscoelastic force of the living tissue. Here, the laser light can capture, for example, extremely small fine particles having a diameter of 100 nm to several tens of μm by the radiation pressure. Therefore, it is possible to measure the viscoelastic force of a living tissue smaller than several cm order or the viscoelastic force of an extremely small region of the living tissue (for example, a region smaller than several cm order).
[0009]
The operating means is a haptic device, and calculates a haptic force (sense of force) to be applied to the haptic device based on the viscoelastic force of the living tissue calculated by the calculating means, and calculates the calculated haptic force. Is preferably further provided to the haptic device.
[0010]
According to this configuration, the haptic device is used as the operating means, and a force sense is calculated from the calculated viscoelastic force of the living tissue, and the force sense is applied to the haptic device. Can experience the viscoelasticity of
[0011]
Further, it is preferable that the detection unit includes a four-divided detector that receives the scattered light of the fine particles via the deflection unit.
[0012]
According to this configuration, since the four-divided detector that receives the scattered light of the fine particles via the deflecting unit is used, the measurement result of the detecting unit is directly expressed as a shift amount, and the measurement procedure of the viscoelastic force is partially simplified. Is done.
[0013]
Further, the operation means may be provided at a remote location by being communicably connected to the deflection means. According to this configuration, the deflection unit can be remotely operated.
[0014]
Further, a cutting laser light output unit that outputs a cutting laser light for cutting the living tissue, a cutting operation unit that receives an operation command from a measurer to deflect the cutting laser light, Cutting laser light deflecting means for deflecting the cutting laser light in response to an operation command received by the cutting operating means, and cutting for guiding the cutting laser light deflected by the cutting laser light deflecting means to the storage means It is preferable to include an optical system for use.
[0015]
According to this configuration, the cutting laser light is deflected in response to an operation command from the operator, guided to the storage unit, and cuts the living tissue by irradiating the living tissue. For this reason, the living tissue can be cut to a desired length, the viscoelastic force of each fragment of the cut living tissue can be individually obtained, and the cell membrane is used as the living tissue. By analyzing changes in force over time, the state of the skeleton of the cell membrane can be diagnosed.
[0016]
BEST MODE FOR CARRYING OUT THE INVENTION
(1st Embodiment)
FIG. 1 is an overall configuration diagram of a measuring device (hereinafter, referred to as a first measuring device) according to a first embodiment of the present invention. The first measuring device includes a laser output device 1 that outputs a laser beam for capturing to capture the fine particles P, a condenser lens 2 that collects the laser light for capturing to capture the fine particles P, A control device 3 for controlling the whole of the first measuring device. Between the laser output device 1 and the condenser lens 2, a deflecting device 5 and a two-wavelength mirror 6 are sequentially arranged toward the downstream side of the laser light. On the upper side of the two-wavelength mirror 6 in the figure, a detector 8 is provided via a condenser lens 7. The detector 8 is electrically connected to the control device 3. An operation unit 9 for adjusting the amount of deflection of the laser light is electrically connected to the control device 3. A container 10 for storing the fine particles P and the living tissue O is provided below the condenser lens 2. The fine particles P and the living tissue O are immersed in, for example, water. The fine particles P are particles made of a dielectric or metal having a diameter of 100 nm to several tens μm. In the first measuring device (the same applies to the second to fourth measuring devices), polystyrene latex particles having a diameter of 2 μm are used as the fine particles P.
[0017]
The laser output device 1 is composed of, for example, a laser diode and a drive circuit for supplying a drive current to the laser diode (both are not shown), and outputs a laser beam for capturing the fine particles P contained in the container 10. The drive circuit is electrically connected to the control device 3, and determines the level of the drive current according to a control signal from the control device, and outputs the level to the laser diode.
[0018]
The condensing lens 2 receives the laser beam output from the two-wavelength mirror 6 and condenses it at a predetermined condensing position CP in the container 10. Further, the scattered light of the fine particles by the laser light is received and guided to the two-wavelength mirror 6 side. The fine particles P are condensed by receiving radiation pressure from the laser beam at the condensing position CP.
[0019]
The deflecting device 5 includes two galvanometer mirrors 51 and 52. The galvanomirror includes a moving coil and a small reflecting mirror attached to the axis of the moving coil. The tilt of the small reflecting mirror is controlled by a current flowing through the moving coil.
[0020]
Here, an X-axis is set on one side in the horizontal direction and a Y-axis is set on one side in the vertical direction on the plane perpendicular to the optical axis of the laser beam, passing through the condensing position CP as shown in FIG. Assume a shape measurement area MA.
[0021]
The galvanomirror 51 determines the amount of laser light deflection in the X-axis direction of the measurement area MA, and the galvanomirror 52 determines the amount of laser light deflection in the Y-axis direction of the measurement area MA. Thus, the position LP of the laser beam on the measurement area MA shown in FIG. 2 is determined. Note that the position LP of the laser beam corresponds to the focusing position CP. More specifically, the galvanomirror 51 adjusts the tilt angle so that X = 0 when the tilt angle is 0 degree and X = X1 (the maximum value on the X axis of the measurement area MA) when the tilt angle is 90 degrees. The amount of deflection of the laser beam in the X direction is determined accordingly. The galvanomirror 52 responds to the inclination angle so that, for example, Y = 0 when the inclination angle is 0 degree, and Y = Y1 (the maximum value on the Y axis of the measurement area MA) when the inclination angle is 90 degrees. The amount of deflection of the laser light in the Y direction is determined.
[0022]
The two-wavelength mirror 6 reflects the laser beam from the deflecting device 5 and guides it to the condenser lens 2 side, and transmits the scattered light of the fine particles P from the condenser lens 2 and guides it to the condenser lens 7 side. . The scattered light transmitted through the two-wavelength mirror 6 is condensed by a condenser lens 7 and guided to a detector 8.
[0023]
The detector 8 includes, for example, a position sensitive detector (PSD), and detects the position of the fine particle P by receiving scattered light of the fine particle P. The PSD has a detector surface for receiving light, and detects the position of the fine particles P in the container 10 from the light receiving position (spot position) of the scattered light on the detector surface. A square light receiving area is set on the detector surface, and this light receiving area corresponds to the measurement area MA. Then, an X axis and a Y axis are set in the light receiving area so as to correspond to the measurement area MA. The detector 8 outputs a voltage signal of a level corresponding to the value of the X coordinate of the spot position and a voltage signal of a level corresponding to the value of the Y coordinate to the control device 3. FIG. 3 is a graph showing the relationship between the spot position (position of fine particles) and the voltage generated by the PSD when the laser beam is moved by 72 μm in parallel with the X axis in the measurement area MA. The output voltage of the PSD is shown, and the horizontal axis shows the position. In FIG. 3, a broken line indicates a laser beam, and a solid line indicates fine particles P. As can be seen from FIG. 3, the voltage value of the fine particles P slightly drifts in the peripheral portion of the measurement area MA, but changes substantially linearly in the central portion.
[0024]
The operation unit 9 is configured by a haptic device electrically connected to the control device 3 and includes a base 91, a main body unit 92, and an operation stick 93. The main body 92 is rotatably attached to the base 91 in a direction indicated by H in FIG. The operation stick 93 is rotatably attached to the main body 92 in the direction shown in FIG. When the measurer holding the operation stick 93 rotates the main unit 92 in the H direction via the operation stick 93, the operation unit 9 outputs an operation command signal of a level corresponding to the rotation amount to the control device 3. Accordingly, the galvanomirror 51 is inclined at an angle corresponding to the rotation amount of the main body 92. When the measurer rotates the operation stick 93 in the V direction, the operation unit 9 outputs an operation command signal of a level corresponding to the rotation amount to the control device 3. As a result, the galvanometer mirror 52 is tilted at an angle corresponding to the rotation amount of the operation stick. Therefore, the measurer moves the laser beam position LP in the measurement area MA to a desired position by operating the operation unit 9 while observing an image of the measurement area MA displayed on the display device 34 described later. be able to.
[0025]
The CCD camera 11 is disposed between the condenser lens 2 and the two-wavelength mirror 6, and photographs the measurement area MA.
[0026]
Next, the principle of laser trapping in which the fine particles P are captured by laser light will be described. The laser trapping technique was developed by Ashkin et al. In 1986. (A. Ashki, JM Dziedzic, JE. Bjorkholm and Steven Chu: Observation of a Single-Beam Gradient Force Optical Trap, Digital Ticker, Digital Telescope, 11-28, 2008). FIG. 3 is a diagram for explaining the principle of laser trapping. When the fine particles P are irradiated with laser light, the laser light is refracted on the surface of the particles having a different refractive index from the surrounding medium, and the traveling direction changes. This causes scattering. Photons that constitute light have momentum, and the momentum is preserved by particles during refraction and scattering. As shown in FIG. 4, when the laser beam traveling in the direction of Pa changes in the direction of Pa ′ due to refraction, the momentum change at this time is directed to the direction of Fa. The momentum change of the photon per unit time is the force acting on the particles. Similarly, when the forces in all the portions where the laser light is applied to the fine particles P are superimposed, as a result, the fine particles P are subjected to a force attracted in the direction of the focal position of the laser light.
[0027]
This is a behavior when the refractive index of the medium is smaller than the refractive index of the fine particles P. Conversely, when the refractive index of the medium is larger than the refractive index of the fine particles, the direction of refraction of the laser beam is reversed. Then, a force acts in a direction away from the laser beam condensing position. Since the first measuring device assumes that the medium is water and the operation target is polystyrene beads or living cells / molecules, the refractive index of the medium is smaller than the refractive index of the fine particles P. Therefore, the fine particles P are captured at the light condensing position CP.
[0028]
FIG. 5 is a block diagram illustrating the function of the control device 3 in the first measurement device. The control device 3 includes a CPU (central processing unit) 31, a ROM (read only memory) 32, a RAM (random access memory) 33, and a display device.
[0029]
The RAM 33 is used as a work area of the CPU 31 and temporarily stores various data. The display device 34 includes a CRT (cathode ray tube) or a liquid crystal panel, and displays an image of the measurement area MA photographed by the CCD camera 11, a measured viscoelastic force of the living tissue, and the like.
[0030]
The CPU 31 functionally includes an operation receiving unit 311, a shift amount calculating unit 312, a viscoelastic force calculating unit 313, and a force sense calculating unit 314.
[0031]
The operation receiving unit 311 receives the operation command signal output from the operation unit 9, generates an inclination command signal for inclining the galvanometer mirrors 51 and 52 at an angle corresponding to the level of the received operation command signal, and deflects the signal. Output to the device 5. Further, the operation receiving unit 311 determines a position LP (XL, YL) on the measurement area MA of the laser beam specified from the inclination angle of the galvanometer mirrors 51, 52. When the tilt angle of the galvanomirror 51 is determined, the value of the X coordinate of the measurement area MA is uniquely determined, and when the tilt angle of the galvanomirror 52 is determined, the value of the Y coordinate of the measurement area MA is uniquely determined. Therefore, the operation receiving unit 311 can determine the position LP of the laser beam in the measurement area MA based on the respective inclination angles of the galvanomirrors 51 and 52.
[0032]
The shift amount calculation unit 312 uses the position PP (XP, YL) of the fine particle P detected by the detector 8 on the measurement area MA and the position LP (XL, YL) of the laser beam determined by the operation reception unit 311. By calculating ΔX = XL−XP and ΔY = YL−YP, the amount of deviation ΔL (ΔX, ΔY) of the fine particle P with respect to the laser light on the measurement area MA is calculated.
[0033]
The viscoelastic force calculation unit 313 calculates the viscoelastic force f (fX, fY) of the living tissue O by substituting the shift amount ΔL (ΔX, ΔY) calculated by the shift amount calculation unit 312 into the equation (1). I do.
[0034]
f = −kΔL + 6πηrv Equation (1)
Here, k is the spring constant of the optical tweezers, η is the viscosity of the liquid (water) in the container 10, r is the radius of the fine particles P, v (v _x , V _y ) Indicates the translation speed of the fine particles P.
[0035]
The fine particles P irradiated with the laser light are captured at the focus position CP by the radiation pressure from the laser light. When the captured fine particles P are pressed against the living tissue O, the fine particles P receive an external force from the living tissue O and are shifted by ΔL from the position LP of the laser beam. Here, the force F acting on the fine particles P is represented by Expression (2).
[0036]
F = kΔL + 6πηrv + f Equation (2)
f is an external force (viscoelastic force of the living tissue O), the first term on the right-hand side is a trapping force acting on the fine particles P, and the second term on the right-hand side is a viscous resistance force from a surrounding medium (water) acting on the translational movement of the fine particles P. It is. Then, assuming that the mass of the fine particle P is m and the acceleration of the fine particle P is a, the equation of motion of the fine particle P is expressed as Expression (3).
[0037]
F = ma Equation (3)
Since the mass m of the fine particles P is very small, if it is negligible compared to the trapping force and the viscous resistance, F = 0 can be set in the equation (3). Then, when Expression (3) is obtained for f, Expression (1) is calculated. Then, assuming that η, r, and v are known in Expression (1), if the value of ΔL is known, the viscoelastic force f can be calculated.
[0038]
The force sense calculation unit 314 calculates a force sense applied to the operation unit 9 including the haptic device by performing a predetermined calculation on the viscoelastic force f calculated by the viscoelastic force calculation unit 313. The macro world where the measurer is present is a world where elastic force is dominant, and the micro world where fine particles P are present is a world where friction and viscosity are dominant. Due to such differences in physical characteristics, it is considered that the method of simply multiplying the position displacement information and force sense information between the macro world and the micro world by a constant is not appropriate in terms of operability. Therefore, the force sense calculation unit 314 does not present the work sense under the micro environment to the measurer as it is, but calculates the force sense so as to match the work sense under the macro environment familiar to the operation of the measurer. ing. Specifically, it is considered that the frictional force with the surrounding medium (water) and the force due to Brownian motion mainly act on the fine particles P. Therefore, the force sense calculation unit 314 approximately approximates these forces.
F _r = -K _r X: Equation (4)
Thus, the force sense is calculated.
Where F _r Is the force acting on the fine particles P, k _r Is the spring constant, and X is the displacement of the fine particles.
[0039]
In the first measuring device, the container 10 corresponds to a storage unit, the laser output device 1 corresponds to a laser output unit, the operation unit 9 corresponds to an operation unit, the deflecting device 5 corresponds to a deflecting unit, The two-wavelength mirror 6 and the condenser lens 2 correspond to a condenser, the detector 8, the operation receiving unit 311 and the shift amount calculator 312 correspond to a detector, and the viscoelastic force calculator 313 corresponds to a calculator. In addition, the force sense calculation unit 314 corresponds to force sense applying means.
[0040]
Next, the operation of the first measuring device will be described. The laser light output from the laser output device 1 shown in FIG. 1 is guided to a light condensing position CP via a deflecting device 5, a two-wavelength mirror 6, and a light converging lens 2. The fine particles P in the container 10 receive the radiation pressure from the laser light, and are captured by the laser light at the focusing position CP. When the measurer operates the operation unit 9, the fine particles P captured by the laser light move in the container 10.
[0041]
FIG. 6 is a graph showing the relationship between the position of the fine particle P and time when the fine particle P is moved 27 μm to the right in parallel with the X axis and subsequently to the left 27 μm. (B) shows a case where one reciprocation is performed in one second, and (b) shows a case where one reciprocation is performed in one second. In both graphs, the vertical axis indicates the position on the X coordinate, and the horizontal axis indicates time. Curve 1 shows the relationship between the position of the fine particles P and time, and curve 2 shows the relationship between the position of the laser beam and time.
[0042]
As shown in (a) and (b), when the laser light is moved to the right, curve 1 is shifted to the right with respect to curve 2, and the laser light is moved to the left. At this time, since the curve 1 is shifted to the left with respect to the curve 2, it can be seen that the fine particles P are moving with a slight delay from the laser light. Comparing (a) and (b), it is found that when the moving speed of the laser light is increased, the amount of delay of the fine particles P with respect to the laser light is increased. The difference between the curves 1 and 2 is the shift amount ΔL of the fine particles P at each time.
[0043]
The fine particles P captured by the laser light shown in FIG. 1 are pressed against the living tissue O. The light scattered by the laser light of the fine particles P is guided to the detector 8 via the condenser lens 2, the two-wavelength mirror 6, and the condenser lens 7, and the position of the fine particles P is detected. Then, the position of the fine particles P detected by the detector 8 is output to the control device 3 as a voltage signal.
[0044]
FIG. 7 is a flowchart showing the processing of the control device 3. In step S1, the operation receiving unit 311 calculates the position LP of the laser beam from the inclination angles of the galvanomirrors 51 and 52. In step S2, the shift amount calculation unit 312 calculates the shift amount ΔL between the two using the position LP of the laser beam calculated by the operation reception unit 311 and the fine particles P detected by the detector 8.
[0045]
In step S3, the viscoelastic force calculation unit 313 calculates the viscoelastic force f by substituting the displacement amount ΔL calculated in step S2 into equation (1). FIG. 8 is a graph showing the relationship between the capturing power of the fine particles P by the laser beam and the viscous resistance of the fine particles P when the fine particles P are moved as shown in FIG. Denotes viscous resistance (unit: μN), and the horizontal axis denotes time. The curve shown by the solid line indicates the viscous resistance, and the curve shown by the broken line indicates the trapping force. In this case, the spring constant k is k = 0.25 μN / m. As shown in Expression (1), the difference between the two curves, that is, the difference between the viscous resistance and the trapping force, is the external force (viscoelastic force of the living tissue O) f applied to the fine particles P.
[0046]
In step S4, the force sense calculation unit 314 calculates a force sense using the viscoelastic force f calculated in step S3. Then, the calculated force sense is given to the operation unit 9. Thus, the measurer receives a resistance force corresponding to the viscoelastic force f from the operation unit 9 at the time of operation, and can sense the viscoelastic force of the living tissue O.
[0047]
As described above, according to the first measuring device, the viscoelastic force f of the living tissue O is measured by capturing the fine particles P having a diameter of 1 micrometer by the laser beam and pressing the fine particles P against the living tissue O. Therefore, it is possible to measure the viscoelastic force f in an extremely small biological tissue on the order of micrometers or an extremely small region of the biological tissue. Further, since the force for capturing fine particles is extremely small (on the order of several tens of femto-Newton to several nano-Newton), the viscoelastic force of the living tissue O can be measured without invasion.
[0048]
(2nd Embodiment)
FIG. 9 is an overall configuration diagram of a measuring device according to the second embodiment of the present invention (hereinafter, referred to as a second measuring device). The second measuring device has a two-wavelength mirror 21 disposed between the laser output device 1 and the deflecting device 5 and a detector 8 above the two-wavelength mirror 21 in the drawing. A split detector was adopted.
[0049]
The two-wavelength mirror 21 transmits the laser light output from the laser output device 1 and guides the laser light to the deflecting device 5 side, receives the scattered light of the fine particles P by the laser light via the deflecting device 5, and receives the received scattered light. The light is reflected and guided to the detector 8 side.
[0050]
FIG. 10 is a diagram showing a light receiving surface of the four-segment detector. The quadrant detector includes four light receiving elements D1 to D4, and the center point S is disposed so as to correspond to the position LP of the laser beam on the measurement area MA. A circular dashed line T including the center point S indicates scattered light received by the quadrant detector. Assuming that the intensity of the scattered light received by each of the light receiving elements D1 to D4 is I1, I2, I3, or I4, the shift amount ΔL is represented by Expression (5).
ΔX = G ((I1 + I2)-(I3 + I4))
ΔY = H ((I1 + I3)-(I2 + I4)) Expression (5)
Here, G and H are proportional constants, which are obtained by experiments. By adopting the four-segment detector, the measurement result of the detector 8 becomes the shift amount ΔL of the fine particle P with respect to the laser beam as it is, and the calculation procedure of the shift amount ΔL can be partially simplified, and the shift amount ΔL can be detected. Accuracy can be increased.
[0051]
In the second measuring device, the detector 8 converts the intensities I1 to I4 into electric signals and outputs the electric signals to the control device 3. The shift amount calculation unit 312 calculates the shift amount ΔL (ΔX, ΔY) using Expression (5) and the intensities I1 to I4.
(Third embodiment)
FIG. 11 shows an overall configuration diagram of a measuring device according to the third embodiment of the present invention (hereinafter, referred to as a third measuring device). The third measuring device enables remote operation by connecting the operation unit 9 to the first measuring device via the communication device 300. The communication device 300 is connected to the control device 3 via a communication line 3A. The communication device 300 is realized by installing software for functioning as a communication device in a normal computer including a CPU, a RAM, a ROM, and the like. The communication device 300 converts an operation command signal from the operation unit 9 into data compliant with, for example, a TCP / IP (Transmission Control Protocol / Internet Protocol) protocol system, and outputs the data to the control device 3. As a transport layer protocol of the TCP / IP protocol system, TCP, which is a connection-type protocol, is adopted to improve communication accuracy.
[0052]
As the communication line 3A, for example, 100BASE / TX is adopted. Accordingly, a communication board corresponding to 100BASE / TX is mounted on the communication device 300 and the control device 3. Further, software for enabling communication with the communication device 300 by TCP / IP is installed in the control device 3.
[0053]
The control device 3 receives the operation command signal from the communication device 300 via the communication line 3A, converts it into a tilt command signal, and outputs the tilt command signal to the deflection device 5. The control device 3 converts the image of the measurement area MA captured by the CCD 11 into data conforming to the TCP / IP protocol system and outputs the data to the communication device 300. The communication device 300 converts the image of the measurement area MA from the received data. It is displayed on the take-out display device 301. Thereby, the measurer can perform a remote operation while viewing the image of the measurement area MA. Further, the control device 3 converts the force sense calculated by the force sense calculation unit 314 into communication data conforming to the TCP / IP protocol system, and transmits the communication data to the communication device 300. The communication device 300 extracts a force sense from the communication data and gives the operation unit 9 a force sense. This allows the measurer to feel the viscoelastic force of the living tissue O.
[0054]
Note that the third measurement device may be capable of remote operation by adopting a configuration in which the operation unit 9 is connected to the second measurement device via the communication device 300.
[0055]
(Fourth embodiment)
FIG. 12 is an overall configuration diagram of a measuring device (fourth measuring device) according to the fourth embodiment of the present invention. A laser output device 41 that outputs laser light (cutting laser light) for cutting the living tissue O to the first measuring device, and a deflecting device 42 that moves the position of the cutting laser light on the measurement area MA. And a two-wavelength mirror 43 for guiding the laser light from the deflecting device 42 to the condenser lens 2 side, and an operation unit 44 for controlling the position of the cutting laser light on the measurement area MA. .
[0056]
The laser output device 41 emits a laser beam having a suitable light amount and wavelength on cutting the living tissue O, for example, a laser beam having a wavelength in an ultraviolet region, or an ultrashort pulse laser beam having a pulse width on a femtosecond scale. Output. The deflection device 42 includes two galvanometer mirrors 421 and 422. As with the galvanometer mirrors 51 and 52, the galvanometer mirrors 421 and 422 change their inclination angles in accordance with an operation command from the operation unit 44, and change the values of the X and Y coordinates of the cutting laser beam on the measurement area MA. Then, the irradiation position of the cutting laser beam is determined.
[0057]
The two-wavelength mirror 43 reflects the cutting laser light from the deflecting device 42 and guides it to the condenser lens 2 side, and transmits the scattered light of the living tissue O and guides it to the detector 8 side.
[0058]
The operation unit 44 is electrically connected to the control device 3 and includes a main body 441 and an operation stick 442. When the measurer tilts the operation stick 442 in a certain direction, an operation command signal indicating the direction in which the operation stick 442 is tilted is output to the control device 3. The operation accepting unit 311 outputs an inclination instruction signal to the galvanometer mirrors 421 and 422 to change the inclination angles of the galvanometer mirrors 421 and 422 so that the cutting laser beam moves in the direction indicated by the operation instruction signal.
[0059]
As described above, according to the fourth measuring apparatus, since the mechanism for cutting the living tissue O is added, the living tissue O is cut to a desired length, and the viscoelastic force of each cut piece of the living tissue O is cut. f can be obtained individually. In addition, a cell membrane is used as the living tissue O, the cell membrane is pulled, the cell membrane in the pulled state is cut using a cutting laser beam, and the viscoelastic force generated when the cell membrane is cut is changed over time. By analyzing the process of the relaxation of the cell membrane, the state of the skeleton of the cell membrane can be diagnosed.
[0060]
In the fourth embodiment, a mechanism for cutting the living tissue O is added to the first measuring device. However, the present invention is not limited to this, and a mechanism for cutting the living tissue O to the second and third measuring devices. May be added. When a mechanism for cutting a living tissue is added to the third measurement device, the operation unit 44 is connected to the communication device 300 shown in FIG. 11, and an operation command signal from the operation unit 44 is transmitted to the communication device 300. Software for outputting to the line 3A may be installed. Thereby, the living tissue O can be cut by remote control.
[0061]
【The invention's effect】
As described above, according to the present invention, since the viscoelastic force of the living tissue is measured by pressing very small fine particles (for example, 1 micrometer in diameter) against the living tissue, an extremely small living tissue, or In addition, it is possible to measure the viscoelastic force in an extremely small area of the living tissue. Further, since the force for capturing fine particles is extremely small (for example, on the order of several tens of femto-Newton to several nano-Newton), the viscoelastic force of the living tissue O can be measured noninvasively.
[Brief description of the drawings]
FIG. 1 shows an overall configuration diagram of a measuring device according to a first embodiment of the present invention.
FIG. 2 is a diagram showing a measurement area.
FIG. 3 is a graph showing a relationship between a spot position (position of fine particles) and a voltage generated by a PSD when a laser beam is moved by 72 μm in parallel with an X axis in a measurement area, and a vertical axis is a PSD. , And the horizontal axis indicates the position.
FIG. 4 is a diagram for explaining the principle of laser trapping.
FIG. 5 is a block diagram illustrating a function of a control device 3 in the first measurement device.
FIG. 6 is a graph showing the relationship between the position of the fine particle P and the time when the fine particle P is moved 27 μm to the right in parallel with the X axis and subsequently to the left 27 μm. (B) shows a case where one reciprocation is performed in one second, and (b) shows a case where one reciprocation is performed in one second.
FIG. 7 is a flowchart showing a process of the control device.
FIG. 8 is a graph showing a relationship between a capturing force of the fine particles P by a laser beam and a viscous resistance force of the fine particles P when the fine particles P are moved as shown in FIG. Indicates force (unit: μN), and the horizontal axis indicates time.
FIG. 9 shows an overall configuration diagram of a measuring device according to a second embodiment of the present invention.
FIG. 10 is a diagram illustrating a light receiving surface of a four-segmented detector.
FIG. 11 shows an overall configuration diagram of a measuring device according to a third embodiment of the present invention.
FIG. 12 shows an overall configuration diagram of a measuring device according to a fourth embodiment of the present invention.
[Explanation of symbols]
1 Laser output device
2 Condensing lens
3 control device
5 Deflection device
6 Two-wavelength mirror
7 Condensing lens
8 Detector
9 Operation section
10 containers
21 Two-wavelength mirror
34 Display device
41 Laser output device
42 Deflection device
43 Two-wavelength mirror
44 Operation unit
51 52 Galvanomirror
311 Operation reception unit
312 shift amount calculation unit
313 Viscoelastic force calculation unit
314 Force sense calculation unit
421 422 Galvano mirror

Claims (5)

A measuring device for measuring a viscoelastic force of a living tissue,
Storage means for storing the biological tissue and the fine particles,
Laser output means for outputting laser light for capturing the fine particles,
Operation means for receiving an operation command from a measurer;
Deflection means for deflecting the laser light, in order to move fine particles captured by the laser light output by the laser output means, in response to an operation command received by the operation means,
Focusing means for guiding the laser light deflected by the deflecting means to the storage means, and for condensing the laser light in the storage means to cause the laser light to capture the fine particles,
Detection means for detecting a shift amount of the fine particles with respect to the laser light generated by pressing the fine particles against the living tissue,
A measuring device comprising: calculating means for calculating a viscoelastic force of the living tissue based on the amount of deviation detected by the detecting means. The operating means is a haptic device,
The haptic device further includes a force sense applying unit that calculates a force sense to be applied to the haptic device based on the viscoelastic force of the living tissue calculated by the calculation unit, and applies the calculated force sense to the haptic device. The measuring device according to claim 1. The measuring apparatus according to claim 1, wherein the detecting unit includes a four-divided detector that receives the scattered light of the fine particles via the deflecting unit. The measuring device according to any one of claims 1 to 3, wherein the operation unit is disposed in a remote place by being communicably connected to the deflection unit. Cutting laser light output means for outputting a cutting laser light for cutting the living tissue,
Cutting operation means for receiving an operation command from a measurer to deflect the cutting laser light,
In accordance with an operation command received by the cutting operation means, cutting laser light deflecting means for deflecting the cutting laser light,
The measuring apparatus according to any one of claims 1 to 4, further comprising: an optical system for guiding the cutting laser light deflected by the cutting laser light deflecting means to the storage means.

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