KR20190063176A - Microscope system - Google Patents

Abstract

According to one embodiment, a microscope system can comprise: a case; an incubator unit disposed in the case for culturing a sample; a microscope unit disposed in a lower part of the incubator unit within the case, and including a light source for irradiating light to the sample and a camera for acquiring an image of the sample by the light irradiated from the light source; and an optical genetic manipulation unit disposed on an upper part of the incubator within the case for controlling the activity of the sample by using light. Therefore, an objective of the present invention is to provide the microscope system capable of simultaneously measuring a fluorescence signal and a phosphorescence signal, and integrating an optical genetic manipulation function, a drug injection function, and a sample collection function.

Description

MICROSCOPE SYSTEM

The present invention relates to a microscope system, and more particularly to a microscopy system in which an optical genetic manipulation function, a drug infusion function, and a sample collection function are integrated.

Recently, a lot of research has been done on the field of "live-cell imaging ".

Such live-cell imaging can be accomplished, for example, by a variety of cell-mediated processes, such as particle transport, protein-protein interaction, enzyme reaction, gene expression, Means a technique of imaging a phenomenon as a visual image.

As such a cell imaging method, there is, for example, fluorescence microscopy. In recent years, a wide-field imaging technique such as epi-fluorescence microscopy or TIRF (total internal reflection fluorescence) Fluorescence microscopy is mainly used.

In addition, as an example of the prior art for fluorescence microscopy for cell imaging as described above, there is a "confocal fluorescence microscope for high-content screening" as disclosed in Korean Patent No. 10-0980306 .

An object of the present invention is to provide a microscope system capable of simultaneously measuring a fluorescence signal and a phosphorescence signal, and integrating an optical genetic manipulation function, a drug injection function, and a sample collection function.

An object according to an embodiment is to provide a microscope system in which an incubator unit, a microscope unit, a photomicrographic operation unit, a drug infusion unit and a sample collection unit are embedded in a case to block external noise.

An object of an embodiment is to provide a microscope system capable of automatically performing long-term imaging without an operator's operation by automatically operating the incubator unit, the drug infusion unit, and the sample collection unit.

An object according to an embodiment is to provide a microscope system in which an incubator unit includes a plurality of chambers, in which a plurality of samples can be cultured at the same time and interactions between the samples can be measured.

An object according to an embodiment is to provide a microscope system capable of precisely manipulating the activity of a biological sample (e.g., a nerve cell, etc.) in milliseconds by means of an optical genetic manipulation unit.

An object according to an embodiment is to provide a microscope system capable of measuring a response of a sample to a drug by a drug infusion unit and a sample collection unit and thereby measuring cell metabolism results (for example, hormone cell growth factor, etc.) .

According to an aspect of the present invention, there is provided a microscope system comprising: a case; An incubator unit disposed in the case for culturing a sample; A microscope unit disposed at a lower portion of the incubator unit in the case, the microscope unit including a light source for irradiating light to the sample and a camera for acquiring an image of the sample with light emitted from the light source; And an optical genetic operation unit disposed on the upper part of the incubator in the case, for controlling the activity of the sample using light.

According to one aspect, the incubator unit includes a plurality of incubation chambers, at least one sample is co-cultivated in the plurality of incubation chambers, and the plurality of incubation chambers are communicated with each other so that one of the plurality of chambers And the substance generated and secreted from the sample may be delivered to the other of the plurality of chambers.

According to one aspect, the microscope unit comprises: a filter wheel disposed in front of the light source; And a lens disposed in front of the camera, wherein the camera is disposed in the same line as the incubator unit, and the light source can be disposed apart from the collinear line to one side.

According to one aspect of the present invention, it is possible to further include a drive unit disposed in the case, for moving the incubator unit and the microscope unit relative to each other.

According to one aspect, the apparatus further includes a drug injection unit for injecting a drug into a sample placed in the incubator unit in the case, and the drug injection unit may be in fluid communication with the incubator unit.

According to one aspect, the apparatus further includes a sample collection unit for collecting the sample to measure the secreted substance in the sample disposed in the incubator unit in the case, and the sample collection unit may be in fluid communication with the incubator unit .

According to one aspect, a fluorescence signal by the light source and a phosphorescence signal by phosphorescence that flows through the case can be simultaneously measured.

According to an aspect of the present invention, there is provided a microscope system comprising: a case; An incubator unit disposed in the case and for culturing a sample; A drug injection unit disposed in the case, the drug injection unit injecting a drug into a sample placed in the incubator unit; A sample collection unit disposed in the case, for collecting a sample to measure a secreted substance in the sample placed in the incubator unit; A microscope unit for acquiring an image of a sample placed in the incubator unit; And a control unit for automatically controlling operations of the incubator unit, the drug infusion unit, the sample collection unit, and the microscope unit.

According to one aspect of the present invention, there is further provided an optical genetic operation unit disposed in the case and adapted to regulate the activity of the sample using light, and the operation of the optical genetic operation unit can be automatically controlled by the control unit.

According to one aspect, the incubator unit comprises a plurality of incubation chambers in which at least one sample is cultured, the drug infusion unit comprising a plurality of drug chambers in which different types of drugs are contained, The plurality of drug chambers may be individually operated and controlled so that the kind of drug injected into at least one of the plurality of culture chambers can be controlled.

According to the microscope system according to the embodiment, the fluorescence signal and the phosphorescence signal can be measured simultaneously, and the optical genetic manipulation function, the drug injection function, and the sample collection function can be integrated.

According to the microscope system according to the embodiment, the incubator unit, the microscope unit, the optical genetic operation unit, the drug infusion unit and the sample collection unit can be embedded in the case to block external noise.

According to the microscope system according to the embodiment, the incubator unit, the drug infusion unit, and the sample collection unit are automatically operated, so that a long-term imaging can be automatically performed without the operator's operation.

According to the microscope system according to the embodiment, the incubator unit includes a plurality of chambers, so that a plurality of samples can be cultured at the same time and the interaction between the samples can be measured.

According to the microscope system according to one embodiment, the activity of biological samples (e.g., nerve cells, etc.) can be precisely manipulated in milliseconds by the optical genetic manipulation unit.

According to the microscope system according to the embodiment, it is possible to measure the response of the sample to the drug by the drug infusion unit and the sample collection unit, and the resultant cell metabolism (for example, hormone cell growth factor, etc.).

Figure 1 shows a microscope system according to one embodiment.
Fig. 2 shows a view in which an incubator unit, a microscope unit, an optical genetic operation unit and a driving unit are combined.
Fig. 3 shows an exploded view of the incubator unit, the microscope unit, the optical genetic operation unit and the drive unit.
Figure 4 shows a plurality of chambers in fluid connection in an incubator unit.
5 shows an automatic operation of a microscope system according to an embodiment by a program embedded in a control unit.

Hereinafter, embodiments will be described in detail with reference to exemplary drawings. It should be noted that, in adding reference numerals to the constituent elements of the drawings, the same constituent elements are denoted by the same reference symbols as possible even if they are shown in different drawings. In the following description of the embodiments, detailed description of known functions and configurations incorporated herein will be omitted when it may make the best of an understanding clear.

In describing the components of the embodiment, terms such as first, second, A, B, (a), and (b) may be used. These terms are intended to distinguish the constituent elements from other constituent elements, and the terms do not limit the nature, order or order of the constituent elements. When a component is described as being "connected", "coupled", or "connected" to another component, the component may be directly connected or connected to the other component, Quot; may be "connected," "coupled," or "connected. &Quot;

The components included in any one embodiment and the components including common functions will be described using the same names in other embodiments. Unless otherwise stated, the description of any one embodiment may be applied to other embodiments, and a detailed description thereof will be omitted in the overlapping scope.

Figure 1 shows a microscope system according to one embodiment, Figure 2 shows a view of an incubator unit, a microscope unit, an optical genetic manipulation unit and a drive unit combined, Figure 3 shows an incubator unit, a microscope unit, FIG. 4 shows a state in which a plurality of chambers are fluidly connected in an incubator unit, and FIG. 5 shows an example in which a microscope system according to an embodiment is automatically FIG.

1 to 3, a microscope system 10 according to an embodiment includes a case 100, an incubator unit 200, a microscope unit 300, a photonic genetic operation unit 400, a drive unit 500, A drug infusion unit 600 and a sample collection unit 700. [

The case 100 may include a plurality of compartments.

The plurality of compartments includes a first compartment 102 disposed at the center, a second compartment 104 disposed at one side of the first compartment 102, and a third compartment 102 disposed at the other side of the first compartment 102. [ (106).

At this time, the first compartment 102 may be provided with a door 1022 that allows access to the internal space of the first compartment 102, and the second compartment 104 may include a door 1022, A door 1042 may be provided to allow access to the space and a door 1062 may be provided in the third compartment 106 to enable access to the inner space of the third compartment 106 .

The incubator unit 200, the microscope unit 300, the optical genetic operation unit 400, the drive unit 500, the drug infusion unit 600 and the sample collection unit 700 can be disposed in the case 100 have.

Concretely, the incubator unit 200, the microscope unit 300, the optical genetic operation unit 400, and the drive unit 500 may be integrally provided in the first compartment 102 of the case 100, The drug infusion unit 600 may be disposed in the second compartment 104 of the case 100 and the sample collection unit 700 may be disposed in the third compartment 106 of the case 100. [

In this way, the incubator unit 200, the microscope unit 300, the optical genetic operation unit 400, the drive unit 500, the drug infusion unit 600 and the sample collection unit 700 are embedded in the case 100, Various experiments and imaging on the sample can be performed in a closed space.

The incubator unit 200 can be configured to cultivate the sample in the case 100. At this time, the sample may include a biological sample such as a nerve cell.

In addition, the incubator unit 200 may be disposed in the upper part of the first compartment 102 of the case 100. [

3 and 4, the incubator unit 200 may include a chamber adapter 210, a lower heater 220, an upper heater 230, and a culture chamber 240.

The lower heater 220 and the upper heater 230 may be disposed at the upper and lower portions of the culture chamber 240 so that the culture chamber 240 may be installed in the culture chamber 240. [ It is possible to adjust the internal temperature of the heater 240.

For example, the incubator unit 200 is driven at a constant temperature, and can be automatically operated according to an NIS program (see FIG. 5) embedded in a control unit (not shown).

In addition, the incubator unit 200 may include a plurality of culture chambers 240.

The plurality of chambers 240 may include a first culture chamber 242 and a second culture chamber 244.

Although FIG. 4 shows a case where a plurality of culture chambers 240 are provided in two, it is needless to say that the number of the culture chambers 240 may be variously provided.

When the plurality of culture chambers 240 include the first culture chamber 242 and the second culture chamber 244 as described above, the two-channel incubator unit 200 can be referred to as a 2-channel incubator unit.

At this time, the first culture chamber 242 and the second culture chamber 244 may be incubated with different samples or the same sample.

For example, when the same sample is cultured in the first culture chamber 242 and the second culture chamber 244, the culture efficiency of the specific sample can be doubled, and the efficiency of the first culture chamber 242 and the second culture chamber 244 When different samples are cultured in the two culture chambers 244, the drug response to various samples and the resultant cellular metabolism can be measured.

In addition, it is natural that only one of the first culture chamber 242 and the second culture chamber 244 can contain the sample and be cultured.

On the other hand, various tubing such as a first tubing T1, a second tubing T2 and a third tubing T3 may be connected to the first incubation chamber 242 and the second incubation chamber 244.

The first tubing T1 allows fluid communication between the first incubation chamber 242 and the drug infusion unit 600, and in particular the drug chamber 610, to allow the drug to be injected into the first culture chamber 242 .

Also, although not specifically shown, the first tubing T1 allows fluid communication between the second incubation chamber 244 and the drug infusion unit 600, particularly the drug chamber 610, Lt; RTI ID = 0.0 > 244 < / RTI >

The second tubing T2 is connected between the first culture chamber 242 and the second culture chamber 244 so that the first culture chamber 242 and the second culture chamber 244 communicate with each other, The interaction between the sample contained in the second culture chamber 242 and the sample contained in the second culture chamber 244 can be measured.

In addition, secretory factors (e.g., hormones, cytokines, etc.) produced and secreted in the sample contained in the first culture chamber 242 are transferred to the second culture chamber 244 through the second tubing T2, The influence of directionality can be studied.

The third tubing T3 allows fluid communication between the second incubation chamber 244 and the sample collection unit 700 so that the sample in the second culture chamber 244 is delivered to the sample collection unit 700 . Although not specifically shown, the third tubing T3 allows fluid communication between the first culture chamber 242 and the sample collection unit 700 so that the sample in the first culture chamber 242 is connected to the sample collection unit (700).

The microscope unit 300 may be configured to acquire an image of a sample in the case 100.

At this time, the microscope unit 300 can be disposed in the lower part of the incubator unit 200 in the first compartment 102 of the case 100, and can be shielded from the external light source.

2 and 3, the microscope unit 300 may include a light source 310, a camera 320, a filter wheel 330, and a lens 340.

The light source 310 may be disposed at one side of the lower part of the incubator unit 200 and adjacent to the second compartment 104 of the case 100.

At this time, the light source 310 may be, for example, a high power 4 colors LED light source for fluorescence. The light source 310 may generate light of a wavelength required for imaging under the control of an NIS program (see FIG. 5) embedded in a control unit (not shown). In particular, LEDs emitting wavelengths of 400nm, 480nm and 560nm are installed to observe blue, green, and red fluorescent light sources, and can be controlled in the millisecond range.

 The camera 320 may be disposed below the incubator unit 200 and the camera 320 and the incubator unit 200 may be disposed on the same line.

At this time, the camera 320 may be provided with, for example, an ultrasensitive EM-CCD camera and may be operated under the control of an NIS program (see FIG. 5) incorporated in a control unit (not shown). In addition, the camera 320 can support the exposing function of the unit of moisture necessary for the exposure of a millisecond range required for fluorescent image capturing and the photographing of a phosphorescent (or luminescent) image. In addition, it is cooled to -100 ° C to minimize noise and provide photon-based sensitivity by electron multiplying.

A camera heater 322 may be disposed in front of the camera 320 to prevent fog formation.

The filter wheel 330 may be disposed in front of the light source 310 and may be arranged to cross the same line on which the camera 320 and the incubator unit 200 are disposed.

At this time, the filter wheel 330 may be provided with a fluorescent filter wheel, and may filter light of a plurality of wavelengths generated by the light source 310.

The lens 340 may be disposed in front of the camera 320 and may be provided with a high resolution 4x lens, for example.

Thus, the microscope unit 300 can simultaneously measure the fluorescence signal for the sample by the light source and the phosphorescence signal for the sample by the phosphorescence that flows through the case 100, if necessary. For example, the fluorescence signal for the sample can be measured when the light source 310 is operated, and the phosphorescence signal for the sample can be measured when the light source 310 is not operated.

The optical genetic manipulation unit 400 may be disposed on top of the microscope unit 300 described above, particularly above the incubator unit 200.

The optical genetic manipulation unit 400 may be provided with, for example, a 2-channel 3-color LED light source for opto-stimulation and may activate the sample by generating light necessary for activation of the optical genetic channel. At this time, the optical genetic manipulation unit 400 can generate 488 nm light that activates the Channelrhodopsin2 series, 590 nm light that activates the Halorhodopsin series, and the like. Further, the optical genetic operation unit 400 can be controlled by, for example, an external operating device or a control unit that generates a TTL signal.

By including the optical genetic operation unit 400 in the case 100 as described above, the activity of a biological sample (for example, a nerve cell or the like) can be precisely manipulated in milliseconds to accurately measure the activity of the biological sample .

The driving unit 500 is for moving the incubator unit 200 and the microscope unit 300 relative to each other and is disposed below the incubator unit 200 to move the incubator unit 200 along the XY axis Stage < RTI ID = 0.0 > 510. < / RTI >

The driving unit 500 may further include a Z axis stage 520 mounted on the lens 340 to adjust the focal distance of the microscope unit 300, Accordingly, the position of the incubator unit 200 can be freely moved with respect to the microscope unit 300, and the focal distance of the microscope unit 300 can be freely adjusted.

Referring again to FIG. 1, a drug infusion unit 600 may be disposed in the second compartment 104 of the case 100.

The drug infusion unit 600 may include a plurality of drug chambers 610.

At this time, the plurality of drug chambers 610 may contain different kinds of drugs or drugs of the same kind.

For example, a plurality of drug chambers 610 may be provided in four, two drug chambers 610 are fluidly connected to the first culture chamber 242, and two drug chambers 610 are provided in the second culture chamber 610. [ So that different drugs can be treated in the sample contained in the first culture chamber 242 and the second culture chamber 244 in fluid communication with the second culture chamber 244.

At this time, the drug infusion unit 600 can be automatically operated according to the NIS program (see Fig. 5) embedded in the control unit (not shown). For example, the individual on / off and flow rates of a plurality of drug chambers 610 and the like can be automatically manipulated. Whereby the kind of drug injected into at least one of the plurality of culture chambers can be controlled.

In addition, the sample collection unit 700 may be disposed in the third compartment 106 of the case 100.

The sample collection unit 700 may collect samples to measure hormones, cytokines, and the like secreted from the samples disposed in the incubator unit 200.

Specifically, the sample collecting unit 700 can collect samples in the range of several tens uL-several mL per minute through the pump disposed at the upper part, and the collected sample is collected through the fraction collector disposed at the bottom Can be classified and collected.

At this time, the sample collecting unit 700 may be automatically operated according to the NIS program (see FIG. 5) embedded in the control unit (not shown), or the operation of the sample collecting unit 700 may be manually operated by the experimenter . For example, the experimenter can specify the number of samples per minute on the fraction collector, allowing the sample collection unit 700 to operate automatically.

As described above, the drug injection unit 600 is disposed in the case 100 to measure the response of the cell to the drug and the result of the cell metabolism (for example, a hormone cell growth factor, etc.).

Further, the operation of the incubator unit 200, the microscope unit 300, the optical genetic operation unit 400, the drug infusion unit 600, and the sample collection unit 700 is automatically controlled by the control unit as described above It is possible to perform long-term imaging automatically without any manipulation by the experimenter.

Although the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, And various modifications and changes may be made thereto without departing from the scope of the present invention. Accordingly, the spirit of the present invention should not be construed as being limited to the embodiments described, and all of the equivalents or equivalents of the claims, as well as the claims set forth below, fall within the scope of the present invention.

10: Microscope system
100: Case
200: Incubator unit
300: Microscope unit
400: Optical genetics operating unit
500: drive unit
600: drug infusion unit
700: Sampling unit

Claims (10)

case;
An incubator unit disposed in the case for culturing a sample;
A microscope unit disposed at a lower portion of the incubator unit in the case, the microscope unit including a light source for irradiating light to the sample and a camera for acquiring an image of the sample with light emitted from the light source; And
An optical genetic operation unit disposed on the upper side of the incubator in the case, for controlling the activity of the sample using light;
/ RTI >
The method according to claim 1,
Wherein the incubator unit includes a plurality of culture chambers,
Wherein at least one sample is co-cultivated in the plurality of culture chambers,
Wherein the plurality of culture chambers are in communication with each other so that material generated and secreted from the sample in one of the plurality of chambers is delivered to the other one of the plurality of chambers.
The method according to claim 1,
The microscope unit comprises:
A filter wheel disposed in front of the light source; And
A lens disposed in front of the camera;
Further comprising:
Wherein the camera is disposed on the same line as the incubator unit,
Wherein the light sources are spaced apart from the collinear side to one side.
The method according to claim 1,
And a drive unit disposed in the case, the drive unit moving the incubator unit and the microscope unit relative to each other.
The method according to claim 1,
Further comprising a drug injection unit for injecting a drug into a sample placed in the incubator unit in the case, wherein the drug injection unit is in fluid connection with the incubator unit.
6. The method of claim 5,
Further comprising a sample collection unit for collecting the sample to measure secreted material in a sample disposed in the incubator unit in the case, wherein the sample collection unit is in fluid connection with the incubator unit.
The method according to claim 1,
Wherein a fluorescence signal by the light source and a phosphorescence signal by phosphorescence that flows through the case are simultaneously measured.
case;
An incubator unit disposed in the case and for culturing a sample;
A drug injection unit disposed in the case, the drug injection unit injecting a drug into a sample placed in the incubator unit;
A sample collection unit disposed in the case, for collecting a sample to measure a secreted substance in the sample placed in the incubator unit;
A microscope unit for acquiring an image of a sample placed in the incubator unit; And
A control unit for automatically controlling operations of the incubator unit, the drug infusion unit, the sample collection unit, and the microscope unit;
/ RTI >
9. The method of claim 8,
Further comprising a photo-genetic manipulation unit disposed in the case and adapted to regulate the activity of the sample using light, wherein the operation of the photo-genetic manipulation unit is automatically controlled by the control unit.
9. The method of claim 8,
Wherein the incubator unit comprises a plurality of culture chambers in which at least one sample is cultured, the drug injection unit comprising a plurality of drug chambers in which different types of drugs are contained,
Wherein the plurality of drug chambers are individually operated and controlled by the control unit so that the kind of drug injected into at least one of the plurality of culture chambers is controlled.

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