KR101487160B1 - Apparatus of magnetic resonance force microscope for biological sample - Google Patents

Apparatus of magnetic resonance force microscope for biological sample Download PDF

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KR101487160B1
KR101487160B1 KR20130094725A KR20130094725A KR101487160B1 KR 101487160 B1 KR101487160 B1 KR 101487160B1 KR 20130094725 A KR20130094725 A KR 20130094725A KR 20130094725 A KR20130094725 A KR 20130094725A KR 101487160 B1 KR101487160 B1 KR 101487160B1
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biological sample
coil housing
coil
hollow portion
sample
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이상갑
최연석
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한국기초과학지원연구원
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01Q—SCANNING-PROBE TECHNIQUES OR APPARATUS; APPLICATIONS OF SCANNING-PROBE TECHNIQUES, e.g. SCANNING PROBE MICROSCOPY [SPM]
    • G01Q60/00—Particular types of SPM [Scanning Probe Microscopy] or microscopes; Essential components thereof
    • G01Q60/50—MFM [Magnetic Force Microscopy] or apparatus therefor, e.g. MFM probes
    • G01Q60/52—Resonance
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
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    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01R33/00—Arrangements or instruments for measuring magnetic variables
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    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
    • G01R33/323—Detection of MR without the use of RF or microwaves, e.g. force-detected MR, thermally detected MR, MR detection via electrical conductivity, optically detected MR
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/42—Screening
    • G01R33/421—Screening of main or gradient magnetic field
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/30—Sample handling arrangements, e.g. sample cells, spinning mechanisms
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/38—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field
    • G01R33/381—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field using electromagnets
    • G01R33/3815—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field using electromagnets with superconducting coils, e.g. power supply therefor

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Abstract

The present invention relates to a magnetic resonance force microscope (MRFM) device for a biological sample, in which the biological is inserted and measured. The magnetic resonance force microscope device for the biological sample comprises a first coil housing which has a superconductive coil embedded therein to generate a magnetic field and which has an annular shape and a hollow portion inside thereof; a second coil housing which is configured to be same as the first coil housing and has another superconductive coil embedded therein to generate the magnetic field together with the superconductive coil of the first coil housing; a shield which connects the first coil housing and the second coil housing with a gap therebetween, prevents a loss of the magnetic field caused by the superconductive coils, and forms a measurement space between the coil housings into which the biological sample is inserted. According to the present invention, since the biological sample is inserted through the shield connecting the coil housings in separated states and then measured, the biological sample can be quickly inserted without needing to separating equipment such as a vacuum pump. Thus, it is possible to acquire accurate MRFM images by measuring the cryogenic biological sample while minimizing damage to the sample.

Description

생체시료용 MRFM 장치{APPARATUS OF MAGNETIC RESONANCE FORCE MICROSCOPE FOR BIOLOGICAL SAMPLE}BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to an MRFM device for biological samples,

본 발명은 생체시료용 MRFM 장치에 관한 것으로, 더욱 상세하게는 박테리아나 살아있는 세포와 같이 생체환경이 유지된 생체시료의 특성을 측정할 수 있는 생체시료용 MRFM 장치에 관한 것이다.
The present invention relates to an MRFM device for biological samples, and more particularly, to an MRFM device for biological samples capable of measuring the characteristics of a biological sample in which the biological environment is maintained, such as bacteria or living cells.

물질을 구성하는 원자의 핵스핀(nuclear spin)이 외부 자기장 하에 있게 되면 외부 자기장을 중심으로 세차운동(precession)을 한다. 이때, 외부에서 외부 자기장에 비례하는 특정한 RF(radio frequency)를 인가하면 공명현상이 관찰되는데, 이를 핵자기공명(NMR:nuclear magnetic resonance)이라 한다.When the nuclear spins of the atoms that make up the material are under the external magnetic field, they precession around the external magnetic field. At this time, when a specific RF (radio frequency) proportional to an external magnetic field is applied from outside, a resonance phenomenon is observed, which is called nuclear magnetic resonance (NMR).

자기공명력현미경(magnetic resonance force microscope,이하 MRFM이라 한다)은 상기와 같은 핵자기 공명현상으로 인해 받게 되는 힘을 광학적 간섭계를 이용하여 얻어지는 신호를 1차원적으로 분석하는 장비로써, 무기물, 고분자, 유기물을 비롯한 다양한 물질의 분자구조 및 성분의 분석에 이용되고 있으며, 생물학, 화학, 물리학, 약리학 등의 다양한 분야에서 폭넓게 사용되고 있다.A magnetic resonance force microscope (hereinafter referred to as MRFM) is a device for analyzing a signal received by using an optical interferometer in one dimension, such as a nuclear magnetic resonance phenomenon, It is widely used in various fields such as biology, chemistry, physics, and pharmacology, and is being used for analyzing molecular structures and components of various materials including organic materials.

통상적인 MRFM은 도 1에 도시된 바와 같이 진공상태의 측정공간을 제공하는 측정부(1)에 생체시료(BS)를 삽입하고, 자기장에 의해서 시료에 포함된 핵에 발생하는 에너지 차와 스핀의 차를 통해 물질을 측정한다.As shown in FIG. 1, a conventional MRFM is a method of inserting a living body sample (BS) into a measuring unit 1 providing a measurement space in a vacuum state and measuring an energy difference and an energy difference Measure the material through the car.

일반적인 MRFM의 측정부(1)는 도 1에 도시된 바와 같이 자기장을 발생시키는 초전도코일(C)이 내장된 원통형의 몸체(2)가 생체시료(BS)의 측정공간(2a)을 이루는 경통(3)에 결합되며, 생체시료(BS)가 중앙에 삽입됨에 따라 미도시된 진공펌프를 통해 경통(3)을 진공상태로 형성한 후, 미도시된 프로브를 통해 생체시료(BS)의 스핀이나 진동을 측정한다.A general MRFM measuring unit 1 includes a cylindrical body 2 having a superconducting coil C incorporated therein for generating a magnetic field as shown in Fig. 3, the barrel 3 is formed in a vacuum state through a vacuum pump (not shown) as the biological sample BS is inserted into the center, and then the spinning of the biological sample BS is performed through a probe Measure the vibration.

이러한 측정부(1)는 초전도코일(C)이 일체형으로 내장됨에 따라 생체시료(BS)를 측정공간(2a)에 삽입하기 위해서는 진공펌프나 프로브를 측정공간(2a)과 분리하여야 하므로 번거로우며, 생체시료(BS)의 삽입시간이 증가됨에 따라 생체시료를 구성하는 세포 등이 손상되어 정확한 측정이 불가능한 문제점이 있다.Since the superconducting coil C is integrated with the measurement unit 1, the measurement unit 1 must separate the vacuum pump or the probe from the measurement space 2a in order to insert the biological sample BS into the measurement space 2a. As the insertion time of the biological sample (BS) is increased, the cells constituting the biological sample are damaged, and accurate measurement can not be performed.

한편, 과거에는 생체시료의 상태를 고려하지 않고 측정하였으나 상온과 같은 악조건 속에서는 스트레스로 인하여 세포들이 죽거나 손상되었다. 이에 따라, 최근에는 생체시료를 급속동결시켜서 극저온상태로 고정하여 측정함으로써 정확한 측정이 이루어지도록 하고 있다.On the other hand, in the past, it was measured without considering the state of biological sample, but in the bad condition such as room temperature, cells were killed or damaged due to stress. Accordingly, in recent years, the biological sample is rapidly frozen and fixed at a cryogenic temperature and measured, so that accurate measurement can be performed.

그러나, 기존의 MRFM 측정부(1)는 전술한 바와 같이 생체시료(BS)의 삽입시간이 증가됨에 따라 생체시료(BS)의 극저온고정이 불가능하여 생체시료(BS)가 훼손되는 문제점이 있다.
However, in the conventional MRFM measuring unit 1, as the insertion time of the biological sample BS is increased as described above, the biological sample BS can not be fixed at a very low temperature, and thus the biological sample BS is damaged.

본 발명은 상기와 같은 종래기술의 문제점을 개선하기 위하여 창출된 것으로, 극저온상태로 동결된 생체시료를 측정공간에 신속하게 삽입함으로써 생체시료가 훼손됨이 없이 측정될 수 있는 생체시료용 MRFM 장치를 제공하기 위함이 그 목적이다.The present invention has been made in order to solve the problems of the prior art as described above, and it is an object of the present invention to provide a MRFM device for biological sample which can be measured without damaging a biological sample by quickly inserting a biological sample frozen at a cryogenic temperature into a measurement space The purpose is to do that.

특히, 생체시료가 유입되는 유입경로나 측정공간을 극저온상태로 유지시킴으로써 극저온으로 냉각된 생체시료의 생체환경을 유지시킬 수 있는 생체시료용 MRFM 장치를 제공하기 위함이 또 하나의 목적이다.
It is another object of the present invention to provide a MRFM device for biological samples capable of maintaining the biological environment of a biological sample cooled at a cryogenic temperature by keeping the inflow path or the measurement space into which the biological sample flows, at a very low temperature.

상기와 같은 목적을 달성하기 위한 본 발명의 생체시료용 MRFM 장치는, 생체시료가 삽입되어 측정되는 MRFM용 장치에 있어서, 자기장을 발생시키는 초전도코일이 내장되고, 내부에 중공을 갖는 환형의 제1 코일하우징; 상기 제1 코일하우징과 동일하게 구성되어 상기 제1 코일하우징의 초전도코일과 함께 자기장을 발생시키는 또 다른 초전도코일이 내장된 제2 코일하우징; 및 상기 제1 코일하우징과 상기 제2 코일하우징을 이격상태로 연결하면서 상기 초전도코일들에 의한 자기장의 손실을 방지하며, 상기 코일하우징들의 사이에 생체시료가 삽입되는 측정공간을 형성하는 쉴드;를 포함하는 것이 바람직하다.In order to achieve the above object, an MRFM apparatus for biological samples according to the present invention comprises: a superconducting coil for generating a magnetic field; and an annular first Coil housing; A second coil housing constructed in the same manner as the first coil housing and incorporating another superconducting coil for generating a magnetic field together with the superconducting coil of the first coil housing; And a shield for preventing loss of a magnetic field due to the superconducting coils while connecting the first coil housing and the second coil housing in a spaced state and forming a measurement space in which a living body sample is inserted between the coil housings; .

상기 쉴드는 예컨대, 상기 제1 코일하우징과 상기 제2 코일하우징의 사이에 개재되어 상기 코일하우징들을 이격상태로 고정하면서 자기장의 손실을 방지하는 쉴드본체; 상기 쉴드본체의 중앙에 형성되어 상기 제1 코일하우징과 상기 제2 코일하우징의 중공들과 연통하면서 상기 측정공간을 형성하는 중공부; 및 상기 중공부와 연통하면서 상기 쉴드본체의 측방에 관로형태로 형성되어 생체시료가 상기 중공부로 로딩되는 관로를 제공하는 로딩관로;를 포함하는 것이 바람직하다.The shield includes, for example, a shield body interposed between the first coil housing and the second coil housing to prevent loss of a magnetic field while fixing the coil housings in a spaced apart state; A hollow portion formed at the center of the shield body and communicating with the hollows of the first coil housing and the second coil housing to form the measurement space; And a loading conduit communicating with the hollow portion and formed in the shape of a tube at a side of the shield body to provide a conduit through which the biological sample is loaded into the hollow portion.

또한, 상기 쉴드는, 상기 로딩관로를 통해 상기 중공부로 로딩되는 생체시료를 극저온상태로 유지시키기 위한 크라이오 로딩수단;을 더 포함하는 것이 바람직하다.The shield may further include a cryo loading means for keeping the biological sample loaded into the hollow through the loading channel at a cryogenic temperature.

상기 크라이오 로딩수단은 예컨대, 생체시료가 냉각상태로 놓여져 고정되는 시료홀더가 구비되고, 상기 로딩관로를 따라 이동하면서 생체시료를 상기 중공부로 삽입시키는 시료스테이지; 및 상기 시료스테이지의 내부를 따라 냉매를 관류시키면서 상기 시료스테이지를 극저온상태로 냉각시키는 냉각라인;을 포함하는 것이 바람직하다.The cryoading unit may include a sample stage having a sample holder in which a biological sample is placed in a cooled state and fixed, and a biological sample is inserted into the hollow while moving along the loading channel; And a cooling line for cooling the sample stage to a cryogenic temperature while allowing the refrigerant to flow along the inside of the sample stage.

이에 더하여, 상기 크라이오 로딩수단은, 상기 시료스테이지의 이동에 따라 상기 중공부를 개폐가능하게 차폐하여 외기가 상기 중공부로 유입되는 것을 방지하는 외기차단게이트;를 더 포함하는 것이 바람직하다.
In addition, it is preferable that the cryoading means further include an outside air blocking gate for shielding the hollow portion so that the hollow portion can be opened or closed according to the movement of the sample stage to prevent the outside air from entering the hollow portion.

본 발명에 따른 생체시료용 MRFM 장치에 의하면, 코일하우징들을 분할상태로 연결하는 쉴드를 통해 생체시료가 삽입되어 측정됨에 따라 진공펌프와 같은 구성장비를 분리하지 않고도 생체시료의 신속한 삽입이 가능하므로, 극저온상태의 생체시료가 손상됨이 최소화된 상태로 측정되어 정확한 MRFM 이미지를 획득할 수 있다.According to the MRFM apparatus for a biological sample according to the present invention, since a biological sample is inserted and measured through a shield connecting the coil housings in a divided state, the biological sample can be inserted quickly without separating constituent equipments such as a vacuum pump, And a precise MRFM image can be obtained by measuring the damage of the biological sample in a cryogenic state to a minimum.

구체적으로, 쉴드본체가 중공부를 통해 코일하우징들을 연통시키면서 코일하우징들과 함께 측정공간을 형성하므로 초전도코일들에 의한 자기장의 손실이 방지되면서 자기장의 중앙에 측정공간이 형성될 수 있다. Specifically, since the shield body forms the measurement space together with the coil housings while communicating the coil housings through the hollow portion, loss of the magnetic field due to the superconducting coils can be prevented, and a measurement space can be formed at the center of the magnetic field.

특히, 생체시료가 크라이오 로딩수단에 의해 극저온상태로 유지되면서 중공부로 로딩됨에 따라 생체시료를 급속동결시킨 경우 생체시료의 극저온 환경을 유지시킬 수 있으므로 생체시료를 정확하게 측정할 수 있다.In particular, when the biological sample is loaded into the hollow portion while being kept at a cryogenic temperature by the cryo loading means, the biological sample can be precisely measured because the cryogenic environment of the biological sample can be maintained when the biological sample is rapidly frozen.

구체적으로, 생체시료가 동결된 상태로 고정되는 시료스테이지가 냉각라인에 의해 극저온으로 냉각된 상태로 로딩관로를 따라 이동하므로, 생체시료의 극저온 고정이 가능하여 좀 더 미세한 생체시료의 이미지를 획득할 수 있다.Specifically, since the sample stage in which the biological sample is frozen in a frozen state is moved along the loading pipe in a state of being cooled to a cryogenic temperature by the cooling line, the biological sample can be fixed at a cryogenic temperature to obtain a more microscopic image of the biological sample .

이에 더하여, 측정공간을 형성하는 중공부가 외기차단게이트에 의해 개폐가능하게 차폐되므로 생체시료의 극저온 상태가 더욱 안정적으로 유지될 수 있다.
In addition, since the hollow portion forming the measurement space is shielded by the outside air blocking gate so as to be openable and closable, the cryogenic state of the biological sample can be more stably maintained.

도 1은 통상적인 MRFM 장치를 나타내는 종단면도.
도 2는 본 발명에 따른 생체시료용 MRFM 장치를 나타내는 절개사시도.
도 3은 도 2에 도시된 생체시료용 MRFM 장치를 나타내는 종단면도.
도 4는 본 발명의 크라이오 로딩수단을 나타내는 사시도.1 is a longitudinal sectional view showing a typical MRFM apparatus.
2 is an exploded perspective view showing an MRFM apparatus for a biological sample according to the present invention.
3 is a longitudinal sectional view showing the MRFM apparatus for biological sample shown in Fig.
4 is a perspective view showing the cryoading means of the present invention.

이하에서 첨부 도면을 참고하여 본 발명의 실시예에 대해서 더욱 상세하게 설명한다. 본 발명을 설명함에 있어서 관련된 공지의 범용적인 기능 또는 구성에 대한 상세한 설명은 생략한다.Hereinafter, embodiments of the present invention will be described in more detail with reference to the accompanying drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted.

본 발명의 일실시에에 따른 생체시료용 MRFM 장치는 도 2에 도시된 바와 같이 제1 코일하우징(100), 제2 코일하우징(200) 및 쉴드(300)를 포함하여 구성된다.The MRFM apparatus for a biological sample according to one embodiment of the present invention includes a first coil housing 100, a second coil housing 200, and a shield 300 as shown in FIG.

제1 코일하우징(100)은 도 2에 도시된 바와 같이 환형으로 형성되어 중앙에 중공(100a)을 가지며, 내부에 초전도코일(C)이 내장되어 자기장을 발생시킨다.The first coil housing 100 is formed in an annular shape as shown in FIG. 2, and has a hollow 100a at the center, and a superconducting coil C is embedded therein to generate a magnetic field.

제2 코일하우징(200)은 도 2에 도시된 바와 같이 제1 코일하우징(100)과 동일하게 구성되어 제1 코일하우징(200)과 이격상태로 연결된다.The second coil housing 200 is constructed in the same manner as the first coil housing 100 as shown in FIG. 2 and is spaced from the first coil housing 200.

즉, 초전도코일(C)은 제1 코일하우징(100) 및 제2 코일하우징(200)에 의해 분할상태의 스플릿코일(split-coil)을 이루면서, 후술되는 쉴드(300)에 의해 이격상태로 연결되어 자기장을 함께 발생시킨다.That is, the superconducting coil C is split and coiled in a split state by the first coil housing 100 and the second coil housing 200, and is connected to the superconducting coil C by a shield 300, Thereby generating a magnetic field together.

쉴드(300)는 도 2에 도시된 바와 같이 제1 코일하우징(100)과 제2 코일하우징(200)을 이격상태로 연결하면서 도 3에 도시된 바와 같이 생체시료(BS)가 삽입되는 측정공간을 코일하우징들(100)(200)의 사이에 형성하는 구성요소이다.3, the shield 300 is connected to the first coil housing 100 and the second coil housing 200 while separating the first coil housing 100 and the second coil housing 200 as shown in FIG. Between the coil housings 100 (200).

이러한 쉴드(300)는 예컨대, 도 2 및 도 3에 도시된 바와 같이 쉴드본체(310), 중공부(320) 및 로딩관로(330)를 포함하여 구성될 수 있다.The shield 300 may include a shield body 310, a hollow portion 320, and a loading conduit 330, as shown in FIGS. 2 and 3, for example.

쉴드본체(310)는 도시된 바와 같이 환형으로 형성됨에 따라 중앙에 중공부(320)를 가지며, 제1 코일하우징(100)과 제2 코일하우징(200)의 사이에 개재된 상태로 고정되어 코일하우징들(100)(200)을 이격상태로 고정한다.The shield body 310 is formed in an annular shape as shown in the figure and has a hollow portion 320 at the center thereof and is fixed in a state interposed between the first coil housing 100 and the second coil housing 200, Thereby fixing the housings 100 and 200 in a separated state.

이러한 쉴드본체(310)는 초전도코일들(C)의 사이를 차폐하는 형태로 고정됨에 따라 초전도코일들(C)에 의해 발생되는 자기장이 외부로 누설되는 것을 방지한다.The shield body 310 is fixed in a shielding manner between the superconducting coils C, thereby preventing the magnetic field generated by the superconducting coils C from leaking to the outside.

예컨대, 쉴드본체(310)는 자기력을 갖는 마그네트로 구성될 수 있다.For example, the shield body 310 may be formed of a magnet having a magnetic force.

중공부(320)는 도 2에 도시된 바와 같이 쉴드본체(310)의 중앙에 형성되어 제1 코일하우징(100)의 중공(100a)과 제2 코일하우징(200)의 중공(200a)을 연통시키면서 중공들(100a)(200a)과 함께 시료(BS)의 측정공간을 이룬다.2, the hollow portion 320 is formed at the center of the shield body 310 so that the hollow 100a of the first coil housing 100 and the hollow 200a of the second coil housing 200 are communicated with each other (BS) together with the hollows (100a) and (200a).

즉, 쉴드본체(310)는 중공부(320)를 통해 제1 코일하우징(100)의 중공(100a) 및 제2 코일하우징(200)의 중공(200a)과 연통됨에 따라 코일하우징들(100)(200)과 함께 중공체를 이루며, 도 3에 도시된 바와 같이 MRFM의 경통(3)에 끼워진 상태로 결합되어 생체시료가 측정되는 측정부(10)를 형성한다.That is, the shield body 310 communicates with the hollow 100a of the first coil housing 100 and the hollow 200a of the second coil housing 200 through the hollow portion 320, (200) to form a hollow body, and is coupled to the barrel (3) of the MRFM as shown in FIG. 3 to form a measurement unit (10) for measuring a biological sample.

이러한 측정부(10)는 경통(3)에 미도시된 진공펌프가 연결되어 진공부압이 제공되면서 미도시된 프로브가 연결됨에 따라 생체시료(BS)의 측정이 이루어진다.In the measurement unit 10, a vacuum pump (not shown) is connected to the barrel 3, and a vacuum negative pressure is provided, and a probe (not shown) is connected to measure the biological sample BS.

여기서, 중공부(320)는 진공펌프에 의한 진공상태를 형성하기 위하여 측정공간을 밀폐시키는 미도시된 차폐부재가 구비될 수도 있다.Here, the hollow portion 320 may be provided with a shielding member (not shown) for sealing the measurement space to form a vacuum state by the vacuum pump.

로딩관로(330)는 도 2에 도시된 바와 같이 중공부(320)와 연통한 상태로 쉴드본체(310)의 일측으로 연장된다. 이러한 로딩관로(330)는 도 3에 도시된 바와 같이 중공부(320)의 측방에 관로를 형성함으로써 생채시료(BS)가 중공부(320)로 로딩되는 이동통로를 제공한다.The loading conduit 330 extends to one side of the shield body 310 while communicating with the hollow portion 320 as shown in FIG. As shown in FIG. 3, the loading conduit 330 provides a passage through which the fresh sample BS is loaded into the hollow portion 320 by forming a channel at the side of the hollow portion 320.

즉, 생체시료(BS)는 로딩관로(330)를 통해 쉴드본체(310)의 중공부(320)로 로딩되어 경통(3)으로 삽입됨에 따라 진공펌프나 프로브 등의 구성장비를 경통(3)이나 코일하우징들(100)(200)에서 분리하지 않고도 신속하게 측정공간(320)으로 삽입될 수 있다.That is, the biological sample BS is loaded into the hollow portion 320 of the shield body 310 through the loading conduit 330 and inserted into the barrel 3 so that the constituent equipment such as a vacuum pump or a probe is inserted into the barrel 3, Or into the measurement space 320 without detaching from the coil housings 100 and 200.

여기서, 생체시료(BS)는 도 3에 도시된 바와 같이 시료스테이지(341)에 탑재된 상태로 로딩관로(330)를 통해 중공부(320)로 삽입될 수 있다. 이에 대해서는 후술한다.Here, the biological sample BS may be inserted into the hollow portion 320 through the loading conduit 330 while being mounted on the sample stage 341 as shown in FIG. This will be described later.

한편, 쉴드본체(310)는 일부분이 개방형으로 형성되거나 개방된 부분에 광학창(optical window)이 설치됨에 따라 측정공간이 투시가능하도록 형성될 수도 있다.Meanwhile, the shield body 310 may be formed such that a measurement space can be opened as an optical window is installed in a part where the shield body 310 is open or formed.

한편, 쉴드(300)는 도 3 및 도 4에 도시된 바와 같이 크라이오 로딩수단(340)을 더 포함하여 구성될 수 있다.3 and 4, the shield 300 may further include a cryoading unit 340. [

크라이오 로딩수단(340)은 생체시료(BS)가 급속동결된 상태로 측정될 경우, 생체시료(BS)를 극저온상태로 유지시키기 위한 수단으로써, 예컨대 시료스테이지(341) 및 냉각라인(342)을 포함하여 구성될 수 있다.The cryo loading means 340 can be used as a means for maintaining the biological sample BS at a cryogenic temperature when the biological sample BS is measured in a rapidly frozen state, As shown in FIG.

시료스테이지(341)는 생체시료(BS)를 탑재한 상태로 로딩관로(330)를 따라 이동하는 부재이다.The sample stage 341 is a member moving along the loading channel 330 with the biological sample BS mounted thereon.

이러한 시료스테이지(341)는 도 4에 도시된 바와 같이 판상으로 형성되면서 시료홀더(341a)가 구비되어 생체시료(BS)가 동결된 상태로 탑재되고, 로딩관로(330)를 따라 이동하면서 중공부(320)를 통해 생체시료(BS)를 경통(3)의 내부로 삽입시키거나 중공부(320)에서 배출시킨다.4, the sample stage 341 is provided with a sample holder 341a so that the biological sample BS is frozen and is moved along the loading pipeline 330, The biological sample BS is inserted into the inside of the lens barrel 3 or discharged through the hollow portion 320 through the lens 320.

여기서, 시료스테이지(341)는 미도시된 틸팅수단에 의해 수직방향이나 수평방향으로 각도가 틸팅되면서 생체시료(BS)의 측정각도를 조절할 수도 있다.Here, the sample stage 341 may adjust the measurement angle of the biological sample BS while tilting the angle in the vertical direction or the horizontal direction by the unillustrated tilting means.

냉각라인(342)은 도 4에 도시된 바와 같이 시료스테이지(341)의 내부를 따라 냉매를 순환시키면서 시료스테이지(341)를 극저온상태로 냉각시킨다.The cooling line 342 cools the sample stage 341 to a cryogenic temperature while circulating the refrigerant along the inside of the sample stage 341 as shown in FIG.

이러한 냉각라인(342)은 지그재그 상태로 배치되는 것이 바람직하며, 미도시된 냉매순환펌프의 작동에 의해 냉매를 순환시킬 수 있다.The cooling line 342 is preferably arranged in a zigzag state, and the refrigerant can be circulated by operating the refrigerant circulation pump (not shown).

여기서, 냉각라인(342)을 순환하는 냉매는 예컨대, 액체질소나 액체헬륨으로 구성될 수 있다.Here, the refrigerant circulating through the cooling line 342 may be composed of, for example, liquid nitrogen or liquid helium.

즉, 생체시료(BS)는 급속동결된 상태로 시료스테이지(341)의 시료홀더(341a)에 탑재되며, 시료스테이지(341)가 냉각라인(342)에 의해 극저온상태로 유지됨에 따라 극저온상태로 측정될 수 있다.That is, the biological sample BS is placed in the sample holder 341a of the sample stage 341 in a rapidly frozen state, and the sample stage 341 is kept at a cryogenic temperature state by the cooling line 342, Can be measured.

따라서, 생체시료(BS)는 세포 등이 훼손됨이 없이 극저온 상태로 측정되어 나노스케일과 같이 고분해능 이미지가 획득될 수 있다.Therefore, the biological sample (BS) can be measured at a cryogenic temperature without destroying the cells, and a high-resolution image such as a nanoscale can be obtained.

다른 한편, 본 발명의 쉴드(300)는 도 3에 도시된 바와 같이 외기차단게이트(343)를 더 포함하여 구성될 수 있다.On the other hand, the shield 300 of the present invention may further include the outside air blocking gate 343 as shown in FIG.

외기차단게이트(343)는 중공부(320)에 외기가 유입되는 것을 방지하는 구성요소로써, 도 3에 도시된 바와 같이 로딩관로(330)와 연통되는 중공부(320)의 일측에 마련되어 중공부(330)를 개폐가능하게 차폐한다.3, the outside air blocking gate 343 is provided at one side of the hollow portion 320 communicating with the loading pipe 330, as shown in FIG. 3, (330) so as to be openable and closable.

이러한 외기차단계이트(343)는 도 3에 도시된 바와 같이 중공부(330)에 삽입된 경통(3)에 설치되어 외기를 차단하는 것이 바람직하다.It is preferable that the outer train stage 343 is installed in the barrel 3 inserted in the hollow portion 330 as shown in FIG. 3 to block the outside air.

구체적으로, 외기차단게이트(343)는 전술한 시료스테이지(341)가 로딩관로(330)의 입구로 유입됨에 따라 개방되며, 시료홀더(341a)에 탑재된 생체시료(BS)가 중공부(320)에 위치한 경통(3)에 삽입됨에 따라 폐쇄되면서 외기의 유입을 차단한다.Specifically, the outside air blocking gate 343 is opened as the sample stage 341 is introduced into the inlet of the loading conduit 330, and the biological sample BS mounted on the sample holder 341a flows into the hollow portion 320 (3), and blocks the inflow of the outside air.

이러한 외기차단게이트(343)는 수동으로 작동하면서 개폐될 수 있으며, 이와 달리 모터방식이나 실린더방식으로 구성되어 자동으로 개폐될 수도 있다.The outside air cut-off gate 343 may be opened and closed manually while being operated by a motor type or a cylinder type.

한편, 외기차단게이트(343)는 복수로 구성되어 로딩관로(330)의 입구측이나 출구측에도 개폐가능하게 설치될 수 있다.
On the other hand, the outside air blocking gate 343 may be formed in a plurality of openings so as to be openable or closable on the inlet side or the outlet side of the loading channel 330.

상기와 같은 구성요소를 포함하는 생체시료용 MRFM 장치를 이용한 생체시료의 측정방법을 설명하면서 본 발명의 작용을 설명한다.The operation of the present invention will be described while explaining a method of measuring a biological sample using the MRFM apparatus for a biological sample including the above components.

측정자는 급속동결된 생체시료(BS)를 측정부(10)에 결합된 경통(3)의 내부로 삽입하여 생체시료의 특성을 측정한다.The measurer measures the characteristics of the biological sample by inserting the rapidly frozen biological sample (BS) into the barrel (3) coupled to the measuring part (10).

구체적으로, 측정자는 급속동결된 생체시료(BS)를 시료스테이지(341)의 시료홀더(341a)에 탑재한 후, 로딩관로(330)를 통해 시료스테이지(341)를 이동시키면서 생체시료(BS)를 중공부(320)에 위치한 경통(3)의 내부로 삽입한다.Specifically, the measurer loads the rapidly frozen biological sample (BS) on the sample holder 341a of the sample stage 341 and then moves the sample stage 341 through the loading channel 330, Is inserted into the inside of the barrel (3) located in the hollow portion (320).

이때, 외기차단게이트(343)는 시료스테이지(341)가 로딩관로(330)로 로딩됨에 따라 개방되고, 생체시료(BS)가 경통(3)의 내부로 삽입됨에 따라 차폐되어 외기의 유입을 차단하며, 시료스테이지(341)는 냉각라인(342)에 의해 냉매가 순환됨에 따라 생체시료(BS)를 극저온상태로 유지시킨다.At this time, the outside air blocking gate 343 is opened as the sample stage 341 is loaded into the loading conduit 330, and is shielded as the biological sample BS is inserted into the barrel 3, And the sample stage 341 keeps the biological sample BS at a cryogenic temperature as the refrigerant is circulated by the cooling line 342.

그리고, 측정자는 생체시료(BS)가 중공부(320)에 위치한 경통(3)으로 로딩되면, 미도시된 진공펌프를 작동시켜서 측정공간(경통(3))을 진공상태로 형성한다.When the biological sample BS is loaded into the barrel 3 located in the hollow portion 320, the measurer operates the vacuum pump (not shown) to form the measurement space (barrel 3) in a vacuum state.

이어서, 측정자는 초전도코일(C)에 전원을 공급하여 측정공간에 자기장을 발생시키고, 미도시된 프로브를 통해 생체시료의 특성을 측정하면서 생체시료(BS)의 측정된 이미지를 획득한다.
Then, the measurer generates a magnetic field in the measurement space by supplying power to the superconducting coil (C), and acquires the measured image of the biological sample (BS) while measuring the characteristics of the biological sample through a probe (not shown).

이상과 같이 본 발명에 따른 생체시료용 MRFM 장치에 의하면, 코일하우징들(100)(200)을 분할상태로 연결하는 쉴드(300)를 통해 생체시료(BS)가 삽입되어 측정됨에 따라 진공펌프와 같은 구성장비를 분리하지 않고도 생체시료(BS)의 신속한 삽입이 가능하므로, 생체시료(BS)가 동결된 상태로 삽입되는 경우에도 손상이 최소화된 상태로 측정되어 정확한 MRFM 이미지를 획득할 수 있다.As described above, according to the MRFM apparatus for a biological sample according to the present invention, when the biological sample BS is inserted and measured through the shield 300 connecting the coil housings 100 and 200 in a divided state, Since the biological sample (BS) can be inserted quickly without separating the same constituent equipment, even if the biological sample (BS) is inserted in a frozen state, the damage can be measured with minimized damage, and an accurate MRFM image can be obtained.

구체적으로, 쉴드본체(310)가 중공부(320)를 통해 코일하우징들(100)(200)을 연통시키면서 코일하우징들(100)(200)과 함께 측정공간을 형성하므로 초전도코일들(C)에 의한 자기장의 손실이 방지되면서 자기장의 중앙에 측정공간이 형성될 수 있다.Concretely, the shield body 310 forms a measurement space together with the coil housings 100 and 200 while communicating the coil housings 100 and 200 through the hollow portion 320, so that the superconducting coils C, The measurement space can be formed at the center of the magnetic field while preventing the loss of the magnetic field caused by the magnetic field.

특히, 생체시료(BS)가 크라이오 로딩수단(340)에 의해 극저온상태로 유지되면서 중공부(320)로 로딩됨에 따라 생체시료(BS)를 급속동결시킨 경우 생체시료(BS)의 극저온 환경을 유지시킬 수 있으므로 생체시료(BS)를 정확하게 측정할 수 있다.In particular, when the biological sample BS is rapidly frozen as it is loaded into the hollow portion 320 while being maintained at a cryogenic temperature by the cryo loading means 340, the cryogenic environment of the biological sample BS It is possible to accurately measure the biological sample (BS).

구체적으로, 생체시료(BS)가 동결된 상태로 고정되는 시료스테이지(341)가 냉각라인(342)에 의해 극저온으로 냉각된 상태로 로딩관로(330)를 따라 이동하므로, 생체시료(BS)의 극저온 고정이 가능하여 나노 스케일과 같이 좀 더 미세한 생체시료(BS)의 이미지를 획득할 수 있다.Specifically, since the sample stage 341, in which the biological sample BS is frozen in a frozen state, moves along the loading pipe 330 while being cooled to a cryogenic temperature by the cooling line 342, Cryogenic fixation is possible, so that an image of a finer biological sample (BS) such as a nanoscale can be obtained.

이에 더하여, 측정공간을 형성하는 중공부(320)가 외기차단게이트(343)에 의해 개폐가능하게 차폐되므로 생체시료(BS)의 극저온 상태가 더욱 안정적으로 유지될 수 있다.
In addition, since the hollow portion 320 forming the measurement space is shielded by the outside air blocking gate 343 so as to be openable and closable, the cryogenic state of the biological sample BS can be more stably maintained.

이상에서 본 발명의 구체적인 실시예를 예로 들어 설명하였으나, 이들은 단지 설명의 목적을 위한 것으로 본 발명의 보호 범위를 제한하고자 하는 것은 아니다. 본 발명의 기술적 사상을 벗어나지 않는 범위 내에서 다양한 치환, 변형 및 변경이 가능하다는 것은 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자에게 자명할 것이다.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. It will be apparent to those skilled in the art that various changes, substitutions, and alterations can be made therein without departing from the spirit of the invention.

10 : 측정부 100 : 제1 코일하우징
200 : 제2 코일하우징 300 : 쉴드
310 : 쉴드본체 320 : 중공부
330 : 로딩관로 340 : 크라이오 로딩수단
341 : 시료스테이지 341a : 시료홀더
342 : 냉각라인 343 : 외기차단게이트10: measuring part 100: first coil housing
200: second coil housing 300: shield
310 shield body 320 hollow
330: Loading channel 340: Cryoading means
341: sample stage 341a: sample holder
342: cooling line 343: outside air blocking gate

Claims (5)

생체시료가 삽입되어 측정되는 생체시료용 MRFM 장치에 있어서,
자기장을 발생시키는 초전도코일이 내장되고, 내부에 중공을 갖는 환형의 제1 코일하우징;
상기 제1 코일하우징과 동일하게 구성되어 상기 제1 코일하우징의 초전도코일과 함께 자기장을 발생시키는 또 다른 초전도코일이 내장된 제2 코일하우징; 및
상기 제1 코일하우징과 상기 제2 코일하우징을 이격상태로 연결하면서 상기 초전도코일들에 의한 자기장의 손실을 방지하며, 상기 제1 코일하우징과 상기 제2 코일하우징의 사이에 생체시료가 삽입되는 측정공간을 형성하는 쉴드;를 포함하고,
상기 쉴드는,
상기 제1 코일하우징과 상기 제2 코일하우징의 사이에 개재되어 상기 제1 코일하우징과 상기 제2 코일하우징을 이격상태로 고정하면서 자기장의 손실을 방지하는 쉴드본체;
상기 쉴드본체의 중앙에 형성되어 상기 제1 코일하우징과 상기 제2 코일하우징의 중공들과 연통하면서 상기 측정공간을 형성하는 중공부; 및
상기 중공부와 연통하면서 상기 쉴드본체의 측방에 관로형태로 형성되어 생체시료가 상기 중공부로 로딩되는 관로를 제공하는 로딩관로;를 포함하는 것을 특징으로 하는 생체시료용 MRFM 장치.
1. A MRFM apparatus for biological samples, wherein a biological sample is inserted and measured,
An annular first coil housing having a superconducting coil for generating a magnetic field and having a hollow therein;
A second coil housing constructed in the same manner as the first coil housing and incorporating another superconducting coil for generating a magnetic field together with the superconducting coil of the first coil housing; And
The first coil housing and the second coil housing being spaced apart from each other to prevent loss of a magnetic field due to the superconducting coils, and a measurement for inserting a living body sample between the first coil housing and the second coil housing And a shield forming a space,
The shield
A shield body interposed between the first coil housing and the second coil housing to prevent magnetic field loss while keeping the first coil housing and the second coil housing apart from each other;
A hollow portion formed at the center of the shield body and communicating with the hollows of the first coil housing and the second coil housing to form the measurement space; And
And a loading conduit formed in the shape of a tube at a side of the shield body in communication with the hollow portion to provide a conduit through which the biological sample is loaded into the hollow portion.
삭제delete 청구항 1에 있어서,
상기 쉴드는,
상기 로딩관로를 통해 상기 중공부로 로딩되는 생체시료를 극저온상태로 유지시키기 위한 크라이오 로딩수단;을 더 포함하는 것을 특징으로 하는 생체시료용 MRFM 장치.
The method according to claim 1,
The shield
Further comprising a cryo loading means for maintaining the biological sample loaded into the hollow through the loading channel at a cryogenic temperature.
청구항 3에 있어서,
상기 크라이오 로딩수단은,
생체시료가 냉각상태로 놓여져 고정되는 시료홀더가 구비되고, 상기 로딩관로를 따라 이동하면서 생체시료를 상기 중공부로 삽입시키는 시료스테이지; 및
상기 시료스테이지의 내부를 따라 냉매를 관류시키면서 상기 시료스테이지를 극저온상태로 냉각시키는 냉각라인;을 포함하는 것을 특징으로 하는 생체시료용 MRFM 장치.
The method of claim 3,
Wherein the cryoading means comprises:
A sample stage having a sample holder in which a biological sample is placed and fixed in a cooled state, and a biological sample is inserted into the hollow portion while moving along the loading channel; And
And a cooling line for cooling the sample stage to a cryogenic temperature while allowing the refrigerant to flow along the inside of the sample stage.
청구항 4에 있어서,
상기 크라이오 로딩수단은,
상기 시료스테이지의 이동에 따라 상기 중공부를 개폐가능하게 차폐하여 외기가 상기 중공부로 유입되는 것을 방지하는 외기차단게이트;를 더 포함하는 것을 특징으로 하는 생체시료용 MRFM 장치.
The method of claim 4,
Wherein the cryoading means comprises:
Further comprising: an outer air blocking gate for shielding the hollow portion so that the hollow portion can be opened and closed in accordance with the movement of the sample stage to prevent the outside air from flowing into the hollow portion.
KR20130094725A 2013-08-09 2013-08-09 Apparatus of magnetic resonance force microscope for biological sample KR101487160B1 (en)

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