Observation equipment

Abstract

Provided is an observation apparatus for a microfluidic device. The observation apparatus observes a microfluidic device having an observation region to be observed and a structure, and has an observation optical system. The observation optical system has a mask that blocks, in a pencil of rays from the observation region, at least some of the rays having undergone an optical action due to the structure present on the path of the pencil of rays up to the observation optical system.

Description

[Technical Field]

[0001] The present invention provides Observation equipment Regarding. [Background technology]

[0002] Patent Document 1 describes a microscope that allows a normal objective lens to be used for special observations and also allows the objective lens to be freely interchangeable. Patent Document 2 describes a microfluidic device observation apparatus and a microfluidic device observation method for observing a test object present inside one or more flow channels in a microfluidic device provided with the flow channels. [Prior art document] [Patent documents] [Patent Document 1] JP 2009-115902 A [Patent Document 2] International Publication No. 2020 / 021604 [General Disclosure]

[0003] In a first aspect of the present invention, there is provided an observation apparatus for a microfluidic device for observing a microfluidic device having an observation region to be observed and a structure, the observation apparatus having an observation optical system, the observation optical system having a mask that blocks at least a portion of light from the observation region that has been optically affected by the structure that is present along the path of the light beam before reaching the observation optical system.

[0004] The observation optical system may have an objective lens that collects the light beam from the observation region, and the mask may be disposed at a position corresponding to the back focal position of the objective lens.

[0005] The imaging device may further include an illumination optical system that illuminates the observation region.

[0006] The observation optical system may have a plurality of masks each having a different blocking area, and the plurality of masks may be configured to be switchable.

[0007] The apparatus may further include a control device, which automatically switches between the plurality of masks depending on the position of the observation region or the type of the microfluidic device to be observed.

[0008] The mask may be configured to be movable in a direction along the optical axis of the observation optical system.

[0009] The apparatus may further include a spatial light modulator, and the mask may be formed by the spatial light modulator.

[0010] The mask may be selected based on information received by the viewing device.

[0011] The above summary of the invention does not list all of the necessary features of the present invention, and subcombinations of these features may also constitute inventions. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a top view showing an example of a schematic configuration of a microfluidic device 100 according to the present embodiment. [Figure 2] 1 is a side view showing an example of a schematic configuration of a microfluidic device 100 according to the present embodiment. [Figure 3] 1 shows an example of a schematic configuration of an observation device 300 in this embodiment. [Figure 4] FIG. 2 is a top view showing an example of a schematic configuration of a mask unit 315 in this embodiment. [Figure 5] FIG. 2 is a schematic diagram showing a first mask 351 in this embodiment. [Figure 6] FIG. 10 is a schematic diagram showing a second mask 352 in this embodiment. [Figure 7] FIG. 10 is a schematic diagram showing a third mask 353 in this embodiment. [Figure 8] FIG. 10 is a schematic diagram showing a fourth mask 354 in this embodiment. [Figure 9]10 is a flowchart showing an example of the operation of the observation device 300 in this embodiment. [Figure 10] An example of a computer 2200 is shown. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will be described below through embodiments of the invention. The following embodiments do not limit the scope of the invention. Not all of the combinations of features described in the embodiments are necessarily essential to the solution of the invention.

[0014] FIG. 1 is a top view showing an example of a schematic configuration of a microfluidic device 100 according to this embodiment. FIG. 2 is a side view showing an example of a schematic configuration of a microfluidic device 100 according to this embodiment. In the following drawings, an XYZ coordinate system is shown. As shown in FIGS. 1 and 2, the microfluidic device 100 has a substantially rectangular parallelepiped shape. Note that the present invention is also applicable to microfluidic devices having other three-dimensional shapes.

[0015] The microfluidic device 100 refers to a chip on which samples corresponding to biological microscopic materials such as DNA, proteins, cells, cell clusters (spheroids, organoids, etc.), and tissues are arranged on a small substrate to analyze gene defects, protein distribution, reaction patterns, etc. The microfluidic device 100 in this embodiment is also called an organ on a chip, a biofunctional chip, an MPS (micro physiological systems), a biochip, a microfluidic chip, a microchip, a cell culture chip, a microchannel chip, etc. The microfluidic device 100 is an object to be observed.

[0016] As an example, the microfluidic device 100 is used for culturing and analyzing cells, cell clusters, and tissues. Furthermore, it is used to add chemical substances (drugs) and evaluate or analyze the reaction between the cultured cells. The microfluidic device 100 may include both a device in which organ cells are cultured and exhibit biological functions, and an "empty" device body in which organ cells have not yet been cultured.

[0017] The microfluidic device 100 can be fabricated using, for example, stereolithography three-dimensional printing techniques and solution cast molding processes. In addition to the above techniques, the microfluidic device 100 can also be fabricated using other microfabrication techniques, such as MEMS (Micro Electro Mechanical Systems).

[0018] 1 and 2, the microfluidic device 100 has multiple layers, and multiple structures 101 such as microchannels are arranged in each layer of the microfluidic device 100. For example, when constructing a small intestine model, an upper channel, mucus, a suction channel, small intestine epithelial cells, a porous membrane, endothelial cells, and a lower channel are layered in this order in the microchannel to construct the small intestine model. Note that the microfluidic device 100 is not limited to having multiple layers.

[0019] Each layer of the microfluidic device 100 is formed, for example, by a substrate. The substrate may be formed, for example, of glass. The substrate may be formed, for example, of a resin material such as polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), polystyrene (PS), or silicon. The microfluidic device 100 may be hollow or solid. The microfluidic device 100 may have a cover that covers the entire microfluidic device 100. It is desirable that the microfluidic device 100 be transparent to irradiating light and observation light.

[0020] The microfluidic device 100 has an observation region 400 that is the object of observation. The observation region 400 of the microfluidic device 100 is the region that the user wishes to observe in the microfluidic device 100, for example, a region where cultured cells are arranged. In the observation region 400, for example, a structure 101 such as a microchannel (e.g., a porous membrane) may be arranged in addition to the cultured cells. The observation region 400 may be a partial region of the porous membrane of the microfluidic device 100. The arrangement (or position) of the observation region 400 in the microfluidic device 100 varies for each individual microfluidic device 100 and can be known in advance.

[0021] The microfluidic device 100 has an obstacle that impedes observation of the observation region 400. The obstacle is, for example, a structure 101 such as a microchannel that is installed in each layer of the microfluidic device 100. When observing the observation region 400, if an obstacle exists between the observation region 400 and the objective lens, the observation light from the observation region 400 is partially blocked or scattered by the obstacle, which impedes observation.

[0022] Note that not all of the structures 101 installed in the microfluidic device 100 are obstacles; whether a structure 101 is an obstacle or not is determined by the positional relationship between the observation area 400 and the structure 101, particularly the optical positional relationship taking into account the field of view and aperture of the objective lens. In FIG. 2, as an example, the hatched structure 101a is considered to be an obstacle. The other structures 101 are not considered to be obstacles. In other words, an obstacle is a structure that exists along the path of the observation light from the observation area to the objective lens, and that causes absorption, reflection, and / or scattering (optical effects).

[0023] FIG. 3 shows an example of the schematic configuration of an observation device 300 according to this embodiment. The observation device 300 according to this embodiment may be, for example, an inverted microscope. As shown in FIG. 3, the observation device 300 includes an illumination optical system 305, an observation optical system 310, a PC 320, a first stage 330, a motor driver 326, and an illumination driver 325. The microfluidic device 100 is placed on the first stage 330 of the observation device 300, and the microfluidic device 100 can be moved in the X and Y directions by moving the first stage 330 in the X and Y directions. The first stage 330 has an observation hole for transmitting observation light from the observation region 400. For simplicity, only the main optical axis is shown, and details of the observation light are omitted.

[0024] The observation optical system 310 has an objective lens 311, a second stage 312 on which the objective lens 311 is placed, an imaging lens 313, a two-dimensional detector 314, and a mask unit 315. The second stage 312 is movable in the Z direction (height direction), and the position of the objective lens 311 in the Z direction can be adjusted. The two-dimensional detector 314 detects observation light from the observation region 400. Examples of the two-dimensional detector 314 include an image sensor such as a CCD (Charge Coupled Device) image sensor or an sCMOS (Scientific Complementary Metal Oxide Semiconductor) image sensor. In addition to the objective lens 311, the observation optical system 310 may further include optical components such as a condenser lens or a dichroic mirror.

[0025] The mask unit 315 is disposed at a position corresponding to the back focal position of the objective lens 311. The position corresponding to the back focal position may be the back focal position itself, or may be a position optically conjugate with the back focal position. The back focal position of the objective lens 311 is allowed to deviate in the optical axis direction from a theoretically uniquely determined back focal position up to 100 times the focal depth of the objective lens 311. In other words, the back focal position is the exit pupil position.

[0026] The PC 320 has a control unit 321 with a CPU and a memory 322, and the control unit 321 reads and executes a control program stored in the memory 322, thereby controlling the operation of the observation device 300. The PC 320 has an input unit 323 that receives various instructions, settings, etc. from the user and transmits them to the control unit 321 of the PC 320, and a display unit 324 that receives commands from the control unit 321 and displays various dialogs, etc. to the user.

[0027] 3, the PC 320 is connected to the first stage 330, second stage 312, and mask unit 315 of the observation device 300 via a motor driver 326, and is able to control the operation of each stage and the mask unit 315 by controlling the motor driver 326. Also, as shown by the dashed dotted line in Fig. 3, the PC 320 is connected to a two-dimensional detector 314, and a detected image is input thereto.

[0028] The PC 320 can control one or more of the illumination intensity, illumination position, and illumination timing of the illumination optical system 305. As shown by the dashed-dotted line in Fig. 3, the PC 320 is connected to the illumination optical system 305 via an illumination driver 325, and can control the on / off and illumination intensity of the illumination members in the illumination optical system 305 by controlling the illumination driver 325. In addition, the PC 320 can control the blinking of the illumination members in the illumination optical system 305 at predetermined timing. The illumination light irradiated onto the observation region 400 via the illumination optical system 305 is, for example, excitation light in the ultraviolet to infrared range in the case of fluorescence observation, and illumination light in the visible to infrared range in the case of bright-field observation and dark-field observation.

[0029] In the case of fluorescence observation, the observation light detected by the two-dimensional detector 314 is fluorescence generated when a fluorescent dye in the observation region 400 is excited by illumination light emitted from the illumination optical system 305, in the case of bright-field observation, it is light that is transmitted, diffracted, and scattered by the observation region 400 from the illumination light emitted from the illumination optical system 305, and in the case of dark-field observation, it is light that is diffracted and scattered by the observation region 400 from the illumination light emitted from the illumination optical system 305. Whether the observation is bright-field or dark-field can be determined by the optical characteristics of the observation optical system 310, such as the NA of the objective lens 311, and the direction of the illumination light from the illumination optical system 305 to the observation region 400, etc.

[0030] FIG. 4 is a top view showing an example of the schematic configuration of the mask unit 315 in this embodiment. The mask unit 315 is a unit in which multiple masks 350 are arranged on a rotary holder. The multiple masks 350 block at least a portion of the observation light beam from the observation region 400 that is absorbed, reflected, and / or scattered (subjected to optical effects) by obstacles. Each of the multiple masks 350 has a region that blocks the light beam from the observation region 400 and a region that transmits the light beam, each having a different shape. FIG. 4 shows, as examples, a mask 350 having an elliptical transmission region (shown as a white outline in the figure), a mask 350 having a semicircular transmission region, and a mask 350 having a rectangular transmission region. The mask unit 315 may be configured to be movable in the optical axis direction.

[0031] The PC 320 automatically switches between multiple masks 350 depending on the type of microfluidic device 100 to be observed. That is, the PC 320 rotates the rotating holder via the motor driver 326 to select an appropriate type of mask 350 for the observation and place it at a position corresponding to the back focal position of the objective lens 311. Note that the shape of the mask 350 may be a shape other than that shown in FIG. 4 . Furthermore, if the microfluidic device 100 has two or more observation regions 400, the mask 350 may be selected based on the observation region 400 of the microfluidic device 100 input to the observation apparatus 300. Alternatively, the mask 350 may be manually switched. Furthermore, the PC 320 may move the rotating holder in the optical axis direction via the motor driver 326 in conjunction with switching the objective lens 311 (changing the magnification).

[0032] Fig. 5 is a schematic diagram showing a first mask 351 in this embodiment. Fig. 5 shows the microfluidic device 100, observation light from the observation region 400 of the microfluidic device 100, the objective lens 311, and the first mask 351. In Fig. 5, other components of the observation apparatus 300 are omitted from the illustration.

[0033] When illumination light is irradiated onto the observation region 400 of the microfluidic device 100 from the illumination optical system 305, observation light is emitted from the observation region 400, as shown in Fig. 5. In Fig. 5, the observation light emitted from the left end of the observation region 400 is shown as observation light 201, the observation light emitted from the center of the observation region 400 is shown as observation light 202, and the observation light emitted from the right end of the observation region 400 is shown as observation light 203. The observation light 201, 202, and 203 are divided into light that is emitted in a lower left direction of the observation region 400 and light that is emitted in a lower right direction of the observation region 400.

[0034] 5, the left end of observation light 201 that emerges from the left end of observation region 400 and enters objective lens 311 is indicated as observation light 201a, and the right end is indicated as observation light 201b. Also, the left end of observation light 202 that emerges from the center of observation region 400 and enters objective lens 311 is indicated as observation light 202a, and the right end is indicated as observation light 202b. Furthermore, the left end of observation light 203 that emerges from the right end of observation region 400 and enters objective lens 311 is indicated as observation light 203a, and the right end is indicated as observation light 203b.

[0035] 5, a structure 101a, which is an obstacle, is located at the lower right position of the observation area 400. Therefore, part of the observation light 202, 203 that is emitted in the lower right direction of the observation area 400 (observation light 202b, 203b) is reflected or scattered by the structure 101a, and a sufficient amount of light does not reach the two-dimensional detector 314. If the two-dimensional detector 314 were to detect and image the observation light in such a state, the image would have uneven brightness that varies from place to place.

[0036] Therefore, in this example, a first mask 351 is disposed to remove observation light that is reflected, scattered, etc. by the obstacle structure 101a and generate an image with approximately uniform brightness overall and less unevenness. The first mask 351 is an example of the mask 350 in FIG. 4. As shown in FIG. 5, the first mask 351 has a transmissive region 351a on the left side and is shaped to transmit observation light that is emitted to the lower left of the observation region 400 and block observation light that is emitted to the lower right of the observation region 400. This makes it possible to generate an image by detecting observation light that has been subjected to the optical effect (influence) of the obstacle structure 101a as much as possible. This results in an image with approximately uniform brightness overall and less unevenness.

[0037] Fig. 6 is a schematic diagram showing the second mask 352 in this embodiment. Fig. 6 shows the microfluidic device 110, a plurality of observation lights from the observation region 400 of the microfluidic device 110, the objective lens 311, and the second mask 352. In Fig. 6, other components of the observation apparatus 300 are omitted from the illustration.

[0038] In FIG. 6, a structure 101a, which is an obstacle, is located at the lower left of the observation region 400. Therefore, a portion of the observation light 201, 202 (observation light 201a, 202a) that is emitted in the lower left direction of the observation region 400 is reflected, scattered, or the like by the structure 101a. In this example, a second mask 352 is located. The second mask 352 is an example of the mask 350. As shown in FIG. 6, the second mask 352 has a transmission region 352a on the right side, and is shaped to transmit the observation light that is emitted in the lower right direction of the observation region 400 and to block the observation light that is emitted in the lower left direction of the observation region 400.

[0039] Fig. 7 is a schematic diagram showing the third mask 353 in this embodiment. Fig. 7 shows the microfluidic device 120, a plurality of observation lights from the observation region 400 of the microfluidic device 120, the objective lens 311, and the third mask 353. In Fig. 7, other components of the observation apparatus 300 are omitted from the illustration.

[0040] In FIG. 7, a structure 101a, which is an obstacle, is located directly below the observation region 400. Therefore, some of the observation light beams 201, 202, and 203 (observation light beams 202a, 203a, 201b, and 202b) that are emitted directly below the observation region 400 are reflected, scattered, or the like by the structure 101a. In this example, a third mask 353 is provided. The third mask 353 is an example of the mask 350. As shown in FIG. 7, the third mask 353 has transmission regions 353a and 353b on the left and right sides, and is shaped to transmit the observation light that is emitted to the lower right and lower left of the observation region 400 and to block the observation light that is emitted directly below the observation region 400.

[0041] Fig. 8 is a schematic diagram showing the fourth mask 354 in this embodiment. Fig. 8 shows the microfluidic device 130, a plurality of observation lights from the observation region 400 of the microfluidic device 130, the objective lens 311, and the fourth mask 354. In Fig. 8, other components of the observation apparatus 300 are omitted from the illustration.

[0042] In FIG. 8, two structures 101a, which are obstacles, are disposed at the lower left and lower right positions of the observation region 400. Therefore, of the observation light beams 201, 202, and 203, a portion (observation light beams 201a, 202a, 202b, and 203b) that are emitted in the lower left and lower right directions of the observation region 400 is reflected, scattered, or the like by the structures 101a. In this example, a fourth mask 354 is disposed. The fourth mask 354 is an example of the mask 350. As shown in FIG. 8, the fourth mask 354 has a transmission region 354a provided in the center and has a shape that transmits the observation light that is emitted directly below the observation region 400 and blocks the observation light that is emitted in the lower left and lower right directions of the observation region 400.

[0043] Although the first mask 351 to the fourth mask 354 have been described as examples of the mask 350 in FIGS. 5 to 8 , the mask 350 may have other shapes and other transparent regions. The shape of the mask 350 may be determined depending on the type of the microfluidic device 100 or the like to be observed. The shape of the mask 350 may be determined based on at least one of the size, area, and position of the observation region 400 of the microfluidic device 100 or the like to be observed within the microfluidic device 100 or the like, the size, area, and position of the obstacle structure 101a within the microfluidic device 100 or the like, and the relative positional relationship between the observation region 400 and the obstacle structure 101a. The shape of the mask 350 may be determined based on the overall shape of the microfluidic device 100 or the like, or the material, such as the refractive index. The shape of the mask 350 may be determined based on the properties of the illumination light from the illumination optical system 305 in the observation apparatus 300.

[0044] 9 is a flowchart showing an example of the operation of the observation device 300 in this embodiment. In step S01, the microfluidic device 100 is placed on the first stage 330. Subsequently, in step S02, chip information, which is individual identification information of the microfluidic device 100, is acquired. The chip information is automatically acquired by the observation device 300 reading identification information such as a barcode printed on the surface of the microfluidic device 100 or an embedded RFID (Radio Frequency Identification) tag.

[0045] Next, in step S03, it is determined whether the microfluidic device 100 is a compatible chip or a non-compatible chip based on the acquired chip information. A compatible chip is a chip that holds information about the microfluidic device 100, such as the arrangement and overall shape of the structure 101 inside the microfluidic device 100, because the information about the microfluidic device 100 is held by the observation device 300, and a non-compatible chip is a chip that the observation device 300 does not hold such information.

[0046] If the microfluidic device 100 is an incompatible chip (NO in step S03), the process proceeds to the next step S04, where an error message is displayed to the user to notify them that the microfluidic device 100 is an incompatible chip. If the microfluidic device 100 is a compatible chip (YES in step S03), the process proceeds to the next step S05, where a message is displayed to prompt the user to press the observation start button.

[0047] When the user presses the observation start button, in the next step S06, the field of view of the microscope serving as the observation device 300 is moved to the observation region 400. The processing of step S06 is performed by the user manually aligning the field of view of the microscope with the observation region 400. However, the processing of step S06 may also be performed automatically by the observation device 300.

[0048] Next, in step S07, the PC 320 selects a mask 350 that is compatible with the microfluidic device 100 to be observed. In the case of a compatible chip, the PC 320 stores in advance a table that associates the chip ID assigned to each microfluidic device 100 (or each observation region 400 of the microfluidic device 100) with the mask ID, and selects an appropriate mask 350 by referring to the table.

[0049] Next, in step S08, the user makes other adjustments to the observation device 300. The various parameters include the illumination intensity, illumination position, and illumination timing of the illumination optical system 305, and the field of view range of the observation device. Next, in step S09, the PC 320 acquires and saves an image of the observation area 400. Next, in step S10, the user checks whether there are any problems with the acquired image. If there are any problems with the acquired image (NO in step S10), the process proceeds to step S11, where the observation conditions are changed, the parameters are adjusted again in step S08, and an image of the observation area 400 is acquired and saved again.

[0050] If there is no problem with the acquired image (YES in step S10), the process proceeds to the next step S12, where it is determined whether or not the microfluidic device 100 has an observation region 400. If there is an observation region 400 (YES in step S12), the process moves to the next observation region in step S13, returns to step S07, and repeats the processes from step S07 to S10. If there is no observation region (NO in step S12), the process proceeds to the next step S13, where the PC 320 performs predetermined image processing on the saved image. At this time, predetermined analysis and evaluation processes such as counting the number of cells, calculating the cell density distribution, and determining whether the cells are alive or dead may be performed. Once image processing has been performed on the saved image, the process ends.

[0051] According to the observation device 300 of the above embodiment, the mask 350 is formed to block at least a portion of the observation light from the observation region 400 that is absorbed, reflected, and / or scattered (subjected to optical effects) by the obstacles, taking into consideration the observation region 400 of the microfluidic device 100 to be observed and the arrangement of the obstacles, i.e., the structures 101a. This makes it possible to detect and generate an image from observation light that has been subjected to the optical effects (influence) of the obstacles, i.e., the structures 101a, as much as possible, excluded, and thus it is possible to generate an image with approximately uniform brightness and little unevenness throughout.

[0052] In the above embodiment, the mask unit 315 is configured as a unit in which multiple masks 350 are arranged on a rotary holder. However, multiple types of masks 350 may be formed using a liquid crystal spatial light modulator (SLM) instead of the mask unit 315. A spatial light modulator is a device that electrically controls each of multiple elements arranged two-dimensionally to modulate the spatial distribution of properties such as amplitude, phase, and polarization of incident light and then emit the modulated light. In a liquid crystal spatial light modulator, the PC 320 controls the state of the liquid crystal for each of the two-dimensionally arranged pixels to select whether to transmit or block incident light, thereby forming multiple types of masks 350 with various transmission regions.

[0053] By using a liquid crystal spatial light modulator, it is possible to generate a mask 350 of any shape in real time. In addition, since it is possible to correct the intensity and phase of the observation light, it can also function as a density filter.

[0054] Various embodiments of the present invention may also be described with reference to flowcharts and block diagrams, where the blocks may represent (1) stages of a process in which operations are performed or (2) sections of an apparatus responsible for performing the operations. Particular stages and sections may be implemented by dedicated circuitry, programmable circuitry provided with computer-readable instructions stored on a computer-readable medium, and / or a processor provided with computer-readable instructions stored on a computer-readable medium. Dedicated circuitry may include digital and / or analog hardware circuitry, and may include integrated circuits (ICs) and / or discrete circuits. Programmable circuitry may include reconfigurable hardware circuitry, including logical AND, OR, XOR, NAND, NOR, and other logic operations, flip-flops, registers, memory elements such as field programmable gate arrays (FPGAs), programmable logic arrays (PLAs), and the like.

[0055] A computer-readable medium may include any tangible device capable of storing instructions that are executed by an appropriate device, such that the computer-readable medium having instructions stored thereon comprises an article of manufacture containing instructions that can be executed to create means for performing the operations specified in the flowcharts or block diagrams. Examples of computer-readable media may include electronic, magnetic, optical, electromagnetic, and semiconductor storage media. More specific examples of computer-readable media may include floppy disks, diskettes, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), electrically erasable programmable read-only memory (EEPROM), static random access memory (SRAM), compact disc read-only memory (CD-ROM), digital versatile disc (DVD), Blu-ray (RTM) disc, memory stick, integrated circuit card, and the like.

[0056] The computer readable instructions may include either assembler instructions, Instruction Set Architecture (ISA) instructions, machine instructions, machine-dependent instructions, microcode, firmware instructions, state-setting data, or source or object code written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Smalltalk®, JAVA®, C++, etc., and conventional procedural programming languages ​​such as the “C” programming language or similar programming languages.

[0057] The computer-readable instructions may be provided to a processor or programmable circuitry of a general-purpose computer, special-purpose computer, or other programmable data processing apparatus, either locally or over a wide-area network (WAN) such as a local area network (LAN), the Internet, etc., which executes the computer-readable instructions to create means for performing the operations specified in the flowcharts or block diagrams. Examples of processors include computer processors, processing units, microprocessors, digital signal processors, controllers, microcontrollers, etc.

[0058] 10 illustrates an example of a computer 2200 in which aspects of the present invention may be embodied, in whole or in part. Programs installed on the computer 2200 may cause the computer 2200 to function as or perform operations associated with an apparatus or one or more sections of the apparatus according to embodiments of the present invention, and / or to perform a process or steps of a process according to embodiments of the present invention. Such programs may be executed by the CPU 2212 to cause the computer 2200 to perform specific operations associated with some or all of the blocks of the flowcharts and block diagrams described herein.

[0059] A computer 2200 according to this embodiment includes a CPU 2212, a RAM 2214, a graphics controller 2216, and a display device 2218, which are interconnected by a host controller 2210. The computer 2200 also includes input / output units such as a communication interface 2222, a hard disk drive 2224, a DVD-ROM drive 2226, and an IC card drive, which are connected to the host controller 2210 via an input / output controller 2220. The computer also includes legacy input / output units such as a ROM 2230 and a keyboard 2242, which are connected to the input / output controller 2220 via an input / output chip 2240.

[0060] The CPU 2212 operates according to programs stored in the ROM 2230 and RAM 2214, thereby controlling each unit. The graphics controller 2216 acquires image data generated by the CPU 2212 into a frame buffer or the like provided in the RAM 2214 or into the graphics controller 2216 itself, and causes the image data to be displayed on the display device 2218.

[0061] The communication interface 2222 communicates with other electronic devices via a network. The hard disk drive 2224 stores programs and data used by the CPU 2212 in the computer 2200. The DVD-ROM drive 2226 reads programs or data from the DVD-ROM 2201 and provides the programs or data to the hard disk drive 2224 via the input / output controller 2220. The IC card drive reads programs and data from an IC card and / or writes programs and data to an IC card.

[0062] The ROM 2230 stores therein a boot program or the like that is executed by the computer 2200 upon activation, and / or programs that depend on the hardware of the computer 2200. The input / output chip 2240 may also connect various input / output units to the input / output controller 2220 via a parallel port, a serial port, a keyboard port, a mouse port, etc.

[0063] The programs are provided by a computer-readable medium such as a DVD-ROM 2201 or an IC card. The programs are read from the computer-readable medium, installed in the hard disk drive 2224, RAM 2214, or ROM 2230, which are also examples of computer-readable media, and executed by the CPU 2212. Information processing described in these programs is read by the computer 2200, and brings about cooperation between the programs and the various types of hardware resources described above. An apparatus or method may be configured by realizing information manipulation or processing in accordance with the use of the computer 2200.

[0064] For example, when communication is performed between the computer 2200 and an external device, the CPU 2212 may execute a communication program loaded into the RAM 2214 and instruct the communication interface 2222 to perform communication processing based on the processing described in the communication program. Under the control of the CPU 2212, the communication interface 2222 reads transmission data stored in a transmission buffer processing area provided in the RAM 2214, the hard disk drive 2224, the DVD-ROM 2201, or a recording medium such as an IC card, and transmits the read transmission data to the network, or writes reception data received from the network to a reception buffer processing area or the like provided on the recording medium.

[0065] The CPU 2212 may also cause all or a necessary portion of a file or database stored on an external recording medium such as the hard disk drive 2224, the DVD-ROM drive 2226 (DVD-ROM 2201), an IC card, etc. to be read into the RAM 2214, and perform various types of processing on the data on the RAM 2214. The CPU 2212 then writes back the processed data to the external recording medium.

[0066] Various types of information, such as various types of programs, data, tables, and databases, may be stored on the recording medium and may undergo information processing. The CPU 2212 may perform various types of processing on data read from the RAM 2214, including various types of operations, information processing, conditional judgment, conditional branching, unconditional branching, information search / replacement, etc., as described throughout this disclosure and specified by the instruction sequences of the programs, and write the results back to the RAM 2214. The CPU 2212 may also search for information in a file, database, etc. on the recording medium. For example, if multiple entries each having an attribute value of a first attribute associated with an attribute value of a second attribute are stored on the recording medium, the CPU 2212 may search for an entry that matches a condition specified by the attribute value of the first attribute from among the multiple entries, read the attribute value of the second attribute stored in the entry, and thereby obtain the attribute value of the second attribute associated with the first attribute that satisfies a predetermined condition.

[0067] The above-described programs or software modules may be stored in a computer-readable medium on or near the computer 2200. A recording medium such as a hard disk or RAM provided in a server system connected to a dedicated communication network or the Internet can also be used as a computer-readable medium, thereby providing the programs to the computer 2200 via the network.

[0068] Although the present invention has been described above using embodiments, the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made to the above embodiments. It is clear from the claims that such modifications and improvements can also be included within the technical scope of the present invention.

[0069] It should be noted that the order of execution of each process, such as operations, procedures, steps, and stages, in the devices, systems, programs, and methods shown in the claims, specifications, and drawings is not specifically stated as "before," "prior to," etc., and that the processes can be performed in any order unless the output of a previous process is used in a subsequent process. Even if the operational flow in the claims, specifications, and drawings is described using "first," "next," etc. for convenience, this does not mean that the processes must be performed in this order. [Explanation of symbols]

[0070] 100 110 120 130 Microfluidic device, 101 Structure, 101a Obstacle, 201-203 Observation light, 325 Lighting driver, 326 Motor driver, 300 Observation device, 310 Observation optical system, 311 Objective lens, 313 Imaging lens, 314 Two-dimensional detector, 315 Mask unit, 321 Control unit, 322 Memory, 323 Input unit, 324 Display unit, 330 First stage, 350-354 Mask, 351a-354a Transmitting area, 2200 Computer, 2201 DVD-ROM, 2210 Host controller, 2212 CPU, 2214 RAM, 2216 Graphics controller, 2218 Display device, 2220 Input / output controller, 2222 Communication interface, 2224 Hard disk drive, 2226 DVD-ROM drive, 2230 ROM, 2240 input / output chip, 2242 keyboard

Claims

1. An observation apparatus for observing a microfluidic device having an observation area to be observed and a structure, An observation optical system and a control device are provided, the observation optical system is a mask that blocks at least a part of light that has been optically affected by the structure that exists along the path of the light beam from the observation area until it reaches the observation optical system, and i) has a plurality of masks with different blocking areas, and the plurality of masks are configured to be switchable, or ii) has a mask that can be switched to a state where the blocking areas are different from each other, the control device automatically switches the mask depending on the position of the observation region or the type of the microfluidic device to be observed; Observation equipment.

2. the observation optical system has an objective lens that condenses the light beam from the observation area, The observation device according to claim 1 , wherein the mask is disposed at a position corresponding to a back focal position of the objective lens.

3. The observation device according to claim 1 , further comprising an illumination optical system that illuminates the observation region.

4. The observation device according to claim 1 , wherein the mask is configured to be movable in a direction along the optical axis of the observation optical system.

5. An observation device as described in claim 1, wherein the mask, which can be switched to different states for the blocking areas, is formed by a spatial light modulator.

6. 10. The observation device of claim 1, wherein the mask is switched based on information received by the observation device.

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