JP2019017344A - Fragile product holding device equipped with expansion mechanism - Google Patents
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本発明は、拡張機構を具備する脆弱物保持デバイスに関する。 The present invention relates to a fragile object holding device including an expansion mechanism.
近年、重症心不全治療の解決策として新しい再生医療の開発が進められている。その一例として、重症心筋梗塞等において組織工学を応用した温度応答性培養皿を用いて作製したシート状細胞培養物を心臓表面に適用する手法などが試みられている。シート状細胞培養物を用いる手法は、大量の細胞を広範囲に安全に移植することが可能であり、例えば、心筋梗塞(心筋梗塞に伴う慢性心不全を含む)、拡張型心筋症、虚血性心筋症、収縮機能障害(例えば、左室収縮機能障害)を伴う心疾患(例えば、心不全、特に慢性心不全)などの治療にとくに有用である。 In recent years, new regenerative medicine has been developed as a solution for treating severe heart failure. As an example, a technique of applying a sheet-shaped cell culture prepared using a temperature-responsive culture dish to which tissue engineering is applied in severe myocardial infarction or the like to the heart surface has been attempted. The technique using a sheet-shaped cell culture can safely transplant a large amount of cells over a wide area, and includes, for example, myocardial infarction (including chronic heart failure associated with myocardial infarction), dilated cardiomyopathy, ischemic cardiomyopathy. It is particularly useful for the treatment of heart diseases (eg, heart failure, particularly chronic heart failure) associated with systolic dysfunction (eg, left ventricular systolic dysfunction).
このようなシート状細胞培養物を臨床応用するには、例えば、作製されたシート状細胞培養物を保存液と共に容器内に収容し、移植が行われる集中治療室などに移送する必要がある。しかしながら、シート状細胞培養物は絶対的な物理的強度が低く、容器を移送する際などに生じる振動で、皺、破れ、破損などが生じることから、この移送作業には高度な技術が要求され、かつ細心の注意を払う必要がある。 In order to clinically apply such a sheet-shaped cell culture, for example, it is necessary to store the prepared sheet-shaped cell culture together with a preservation solution in a container and transfer it to an intensive care unit where transplantation is performed. However, sheet-like cell cultures have low absolute physical strength, and vibrations that occur when containers are transported can cause wrinkles, tears, breakage, etc., so this transport operation requires advanced techniques. And it is necessary to pay close attention.
このようなニーズに応えるために、種々の方法や容器が開発されている。たとえば、下記特許文献1に記載された膜状組織の保存輸送容器は、収容部内を気体層が形成されることがない程度に保存液で満たすことで、保存液が波打ったり流動したりせず、結果的に、膜状組織に振動が伝わらず、膜状組織の破損を防止できるようになっている。 In order to meet such needs, various methods and containers have been developed. For example, in the storage and transport container for a membranous tissue described in Patent Document 1 below, the storage liquid may be waved or flowed by filling the storage portion with the storage liquid to such an extent that a gas layer is not formed. As a result, no vibration is transmitted to the membranous tissue, and the membranous tissue can be prevented from being damaged.
また、下記特許文献2には、培養組織の包装容器であって、容器本体と、蓋体と、培養組織を載置可能インナートレイとを備える、包装容器が記載されている。かかる包装容器は、包装容器内において、培養組織をインナートレイに載置して収容するとともに、インナートレイ操作部を予め包装容器内に準備しておくことで、インナートレイの容器本体からの取り出しを容易化できるようになっている。しかしながら、かかる包装容器を用いた場合、包装容器内に気泡が残るなどのおそれがある。 Patent Document 2 below describes a packaging container for a cultured tissue, which includes a container body, a lid, and an inner tray on which the cultured tissue can be placed. In such a packaging container, the cultured tissue is placed and accommodated in the inner tray in the packaging container, and the inner tray operation unit is prepared in the packaging container in advance so that the inner tray can be removed from the container body. It can be made easier. However, when such a packaging container is used, there is a risk that bubbles remain in the packaging container.
さらに、下記特許文献3には、培養細胞シートを運搬するための包装体が記載されている。かかる包装体は、リッドで密封する際に若干の液体培地と共に空気を排除することによって、運搬時に培養細胞シート包装体が揺れても、液体培地中を気泡が移動したりすることがないため、培養細胞シートのズレや欠損を防止できるようになっている。 Further, Patent Document 3 below describes a package for transporting a cultured cell sheet. Such a package, when sealed with a lid, excludes air together with some liquid medium, even if the cultured cell sheet package shakes during transportation, bubbles do not move in the liquid medium, It is possible to prevent displacement and loss of the cultured cell sheet.
このような中、本発明者らは、液体中の脆弱物の形状を保持する手段を開発するにあたり、蓋をした状態の容器内から気泡(気体)を取り除くことが難しいなどの問題に直面した。したがって、本発明の目的は、そのような問題を解決し、液体中の脆弱物の形状を安定的に保持するためのデバイスを提供することにある。 Under such circumstances, the present inventors faced problems such as difficulty in removing bubbles (gas) from the inside of the covered container in developing the means for maintaining the shape of the fragile substance in the liquid. . Accordingly, an object of the present invention is to provide a device for solving such problems and stably maintaining the shape of a fragile substance in a liquid.
本発明者らは、上記課題を解決するために鋭意研究を進める中で、蓋で容器を密閉すると容器内の気体を排出できなくなり、液密空間を上手く形成できないことに着眼したところ、さらに研究を進めた結果、蓋部材と容器との間に拡張可能な部材を入れることで、問題が解決できることを見出し、本発明を完成させた。 The inventors of the present invention, while pursuing earnest research to solve the above problems, focused on the fact that if the container is sealed with a lid, the gas in the container cannot be discharged and the liquid-tight space cannot be formed well. As a result, the inventors have found that the problem can be solved by inserting an expandable member between the lid member and the container, and the present invention has been completed.
すなわち本発明は、以下に関する。
[1]脆弱物を収容するための有底筒状の容器、容器を密閉する蓋部材、および容器と蓋部材との間に介在する拡張部材を含む、デバイスであって、拡張部材は、収縮形態と、該収縮形態よりも拡張して容器と密着する拡張形態とに移行可能であり、拡張部材が、収縮形態から拡張形態への移行に伴い脆弱物および液体を収容した容器内空間の気体および液体を押し出して容器と密着することで液密空間を形成する、前記デバイス。
[2]押し出された気体および液体を排出するための排出経路を有する、上記[1]に記載のデバイス。
[3]拡張部材で容器に液密空間を形成した後に、蓋部材で容器を密閉することができる、上記[1]または[2]に記載のデバイス。
[4]容器が、下部および該下部の内径より大きな内径を有する上部を含み、拡張形態において、拡張部材が下部の開口部に密着する、上記[1]〜[3]のいずれか一つに記載のデバイス。
That is, the present invention relates to the following.
[1] A device including a bottomed cylindrical container for containing a fragile substance, a lid member for sealing the container, and an expansion member interposed between the container and the lid member, the expansion member contracting Gas in the internal space of the container containing the fragile material and the liquid as the expansion member moves from the contracted form to the expanded form. And the device for forming a liquid-tight space by extruding the liquid and closely contacting the container.
[2] The device according to [1] above, which has a discharge path for discharging the extruded gas and liquid.
[3] The device according to [1] or [2] above, wherein after the liquid-tight space is formed in the container with the expansion member, the container can be sealed with the lid member.
[4] In any one of the above [1] to [3], the container includes a lower portion and an upper portion having an inner diameter larger than the inner diameter of the lower portion, and in the expanded configuration, the expansion member is in close contact with the lower opening. The device described.
[5]押し出された気体および液体を受容するための受容空間を有する、上記[1]〜[4]のいずれか一つに記載のデバイス。
[6]拡張部材が、拡張形態において容器内空間に向けて突出する凸部を有し、該凸部の水平断面積は垂直下方に向かうほど小さい、上記[1]〜[5]のいずれか一つに記載のデバイス。
[7]脆弱物がシート状細胞培養物である、上記[1]〜[6]のいずれか一つに記載のデバイス。
[8]シート状細胞培養物が、積層体である、上記[7]に記載のデバイス。
[5] The device according to any one of [1] to [4] above, which has a receiving space for receiving the extruded gas and liquid.
[6] Any of the above-mentioned [1] to [5], wherein the expansion member has a convex portion protruding toward the inner space of the container in the expanded configuration, and the horizontal cross-sectional area of the convex portion is smaller as it goes vertically downward. A device according to one.
[7] The device according to any one of [1] to [6], wherein the fragile material is a sheet-shaped cell culture.
[8] The device according to [7] above, wherein the sheet-shaped cell culture is a laminate.
本発明のデバイスによれば、容器内を確実に液密空間にできるため、泡(気体)が容器内に入らず、容器の揺れによって泡が容器内で動いて脆弱物を破損することがない。特に、脆弱物がシート状細胞培養物の積層体である場合に、気泡が移動して、積層体がズレたり欠損したりすることがない。また、製造段階で容器や蓋の寸法にズレが生じても、確実に容器内を液密にすることができるため、設計コストや製造コストの点において大きなメリットがある。 According to the device of the present invention, since the inside of the container can be surely made into a liquid-tight space, bubbles (gas) do not enter the container, and the bubbles do not move inside the container due to the shaking of the container and damage fragile materials. . In particular, when the fragile material is a laminated body of sheet-like cell cultures, bubbles do not move and the laminated body is not displaced or lost. In addition, even if the container or the lid is displaced in the manufacturing stage, the inside of the container can be surely liquid-tight, which is a great merit in terms of design cost and manufacturing cost.
本発明の一側面は、脆弱物を収容するための有底筒状の容器、容器を密閉する蓋部材、および容器と蓋部材との間に介在する拡張部材を含む、デバイスであって、拡張部材は、収縮形態と、該収縮形態よりも拡張して容器と密着する拡張形態とに移行可能であり、拡張部材が、収縮形態から拡張形態への移行に伴い脆弱物および液体を収容した容器内空間の気体および液体を押し出して容器と密着することで液密空間を形成する、前記デバイスに関する。 One aspect of the present invention is a device comprising a bottomed cylindrical container for accommodating a fragile material, a lid member for sealing the container, and an expansion member interposed between the container and the lid member, The member is capable of transitioning to a contracted form and an expanded form that expands more closely than the contracted form and is in close contact with the container, and the expansion member contains a fragile substance and a liquid along with the transition from the contracted form to the expanded form. It is related with the said device which forms liquid tight space by extruding the gas and liquid of internal space, and closely_contact | adhering with a container.
本明細書における脆弱物とは、物理的強度が低く、液体の揺れなどによって、破れ、破損、変形などが生じ得る物体をいう。かかる物体としては、薄肉部を有する物体、帯形状を有する物体、シート形状を有する物体などが挙げられる。かかるシート形状を有する物体としては、とくに限定されないが、シート状構造物、例えば、シート状細胞培養物などの、生体由来材料からなる平膜上の膜組織や、プラスチック、紙、織布、不織布、金属、高分子、脂質といった種々の材質のフィルム等が含まれる。これらのうち、液体中で難分解性のもの、液体中で難崩壊性のものなどが好ましい。シート状構造物は、多角形や円形などであってもよく、幅、厚み、直径などは一様であってもなくてもよい。本発明におけるシート状構造物は、1枚のみを単層の状態で使用してもよいし、2枚以上を重ねた積層の状態で使用してもよい。後者の場合、積層の各層は互いに連結していても、連結していなくてもよく、連結している場合は、重なり合っている部分が全て連結していても、部分的に連結していてもよい。 In this specification, a fragile material refers to an object that has low physical strength and can be broken, damaged, deformed, or the like due to liquid shaking. Examples of such an object include an object having a thin portion, an object having a band shape, and an object having a sheet shape. The object having such a sheet shape is not particularly limited, but a sheet-like structure, for example, a membrane structure on a flat membrane made of a biological material such as a sheet-like cell culture, plastic, paper, woven fabric, and non-woven fabric. , Films of various materials such as metals, polymers and lipids. Of these, those that are hardly decomposable in liquid and those that are hardly disintegrable in liquid are preferable. The sheet-like structure may be polygonal or circular, and the width, thickness, diameter, etc. may or may not be uniform. In the present invention, only one sheet-like structure may be used in a single layer state, or two or more sheets may be used in a laminated state. In the latter case, the layers of the stack may or may not be connected to each other, and in the case of being connected, all overlapping portions may be connected or partially connected. Good.
本明細書において、シート状細胞培養物とは、細胞が互いに連結してシート状になったものをいう。細胞同士は、直接(接着分子などの細胞要素を介するものを含む)および/または介在物質を介して、互いに連結していてもよい。介在物質としては、細胞同士を少なくとも物理的(機械的)に連結し得る物質であれば特に限定されないが、例えば、細胞外マトリックスなどが挙げられる。介在物質は、好ましくは細胞由来のもの、特に、シート状細胞培養物を構成する細胞に由来するものである。細胞は少なくとも物理的(機械的)に連結されるが、さらに機能的、例えば、化学的、電気的に連結されてもよい。シート状細胞培養物は、1の細胞層から構成されるもの(単層)であっても、2以上の細胞層から構成されるもの(積層(多層)、例えば、2層、3層、4層、5層、6層など)であってもよい。また、シート状細胞培養物は、細胞が明確な層構造を示すことなく、細胞1個分の厚みを超える厚みを有する3次元構造を有してもよい。例えば、シート状細胞培養物の垂直断面において、細胞が水平方向に均一に整列することなく、不均一に(例えば、モザイク状に)配置された状態で存在していてもよい。 In the present specification, the sheet-shaped cell culture refers to a cell-shaped culture in which cells are connected to each other. The cells may be linked to each other directly (including those via cell elements such as adhesion molecules) and / or via intervening substances. The intervening substance is not particularly limited as long as it is a substance that can connect cells at least physically (mechanically), and examples thereof include an extracellular matrix. The intervening substance is preferably derived from cells, particularly derived from cells constituting the sheet-shaped cell culture. The cells are at least physically (mechanically) connected, but may be further functionally, for example, chemically or electrically connected. The sheet-shaped cell culture is composed of one cell layer (single layer) or composed of two or more cell layers (stacked (multilayer), for example, two layers, three layers, four layers) Layer, 5 layers, 6 layers, etc.). Further, the sheet-shaped cell culture may have a three-dimensional structure having a thickness exceeding the thickness of one cell without the cells showing a clear layer structure. For example, in the vertical cross section of the sheet-shaped cell culture, the cells may be present in a non-uniform (for example, mosaic) arrangement without being uniformly aligned in the horizontal direction.
本明細書におけるシート状細胞培養物は、上記の構造を形成し得る任意の細胞から構成される。かかる細胞の例としては、限定されずに、接着細胞(付着性細胞)を含む。接着細胞は、例えば、接着性の体細胞(例えば、心筋細胞、線維芽細胞、上皮細胞、内皮細胞、肝細胞、膵細胞、腎細胞、副腎細胞、歯根膜細胞、歯肉細胞、骨膜細胞、皮膚細胞、滑膜細胞、軟骨細胞など)および幹細胞(例えば、筋芽細胞、心臓幹細胞などの組織幹細胞、胚性幹細胞、iPS(induced pluripotent stem)細胞などの多能性幹細胞、間葉系幹細胞等)などを含む。体細胞は、幹細胞、特にiPS細胞から分化させたものであってもよい。シート状細胞培養物を形成し得る細胞の非限定例としては、例えば、筋芽細胞(例えば、骨格筋芽細胞など)、間葉系幹細胞(例えば、骨髄、脂肪組織、末梢血、皮膚、毛根、筋組織、子宮内膜、胎盤、臍帯血由来のものなど)、心筋細胞、線維芽細胞、心臓幹細胞、胚性幹細胞、iPS細胞、滑膜細胞、軟骨細胞、上皮細胞(例えば、口腔粘膜上皮細胞、網膜色素上皮細胞、鼻粘膜上皮細胞など)、内皮細胞(例えば、血管内皮細胞など)、肝細胞(例えば、肝実質細胞など)、膵細胞(例えば、膵島細胞など)、腎細胞、副腎細胞、歯根膜細胞、歯肉細胞、骨膜細胞、皮膚細胞等が挙げられる。本明細書においては、単層の細胞培養物を形成するもの、例えば、筋芽細胞などが好ましく、とくに好ましくは骨格筋芽細胞である。 The sheet-like cell culture in this specification is comprised from the arbitrary cells which can form said structure. Examples of such cells include, but are not limited to, adherent cells (adherent cells). Adherent cells are, for example, adherent somatic cells (eg, cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, kidney cells, adrenal cells, periodontal cells, gingival cells, periosteum cells, skin Cells, synovial cells, chondrocytes, etc.) and stem cells (eg, tissue stem cells such as myoblasts, cardiac stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.) Etc. Somatic cells may be differentiated from stem cells, particularly iPS cells. Non-limiting examples of cells that can form a sheet-like cell culture include, for example, myoblasts (eg, skeletal myoblasts), mesenchymal stem cells (eg, bone marrow, adipose tissue, peripheral blood, skin, hair roots) , Muscle tissue, endometrium, placenta, cord blood, etc.), cardiomyocytes, fibroblasts, cardiac stem cells, embryonic stem cells, iPS cells, synovial cells, chondrocytes, epithelial cells (eg, oral mucosal epithelium) Cells, retinal pigment epithelial cells, nasal mucosal epithelial cells, etc.), endothelial cells (eg, vascular endothelial cells), hepatocytes (eg, liver parenchymal cells), pancreatic cells (eg, islet cells), kidney cells, adrenal glands Examples include cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells and the like. In the present specification, those forming a monolayer cell culture, such as myoblasts, are preferred, and skeletal myoblasts are particularly preferred.
細胞は、細胞培養物による治療が可能な任意の生物に由来し得る。かかる生物には、とくに限定されないが、例えば、ヒト、非ヒト霊長類、イヌ、ネコ、ブタ、ウマ、ヤギ、ヒツジなどが含まれる。また、シート状細胞培養物の形成に用いる細胞は1種類のみであってもよいが、2種類以上の細胞を用いることもできる。本発明の好ましい態様において、細胞培養物を形成する細胞が2種類以上ある場合、最も多い細胞の比率(純度)は、細胞培養物製造終了時において、例えば骨格筋芽細胞の場合、65%以上、好ましくは70%以上、より好ましくは75%以上である。 The cells can be derived from any organism capable of being treated with cell culture. Such organisms include, but are not limited to, humans, non-human primates, dogs, cats, pigs, horses, goats, sheep, and the like. Further, only one type of cell may be used for forming the sheet-shaped cell culture, but two or more types of cells may be used. In a preferred embodiment of the present invention, when there are two or more types of cells forming a cell culture, the highest cell ratio (purity) is 65% or more at the end of cell culture production, for example, in the case of skeletal myoblasts. , Preferably 70% or more, more preferably 75% or more.
本発明におけるシート状細胞培養物は、スキャフォールド(細胞培養時の足場)に細胞を播種し、培養することによって得られるシート形状の培養組織などでもよいが、好ましくは、細胞培養物を構成する細胞由来の物質のみからなり、それら以外の物質を含まない。
シート状細胞培養物は、任意の既知の手法によって製造されたものであってよい。
The sheet-shaped cell culture in the present invention may be a sheet-shaped cultured tissue obtained by seeding and culturing cells in a scaffold (scaffold during cell culture), but preferably constitutes a cell culture. Consists only of cell-derived substances and does not contain any other substances.
The sheet-like cell culture may be produced by any known technique.
本発明の一態様において、シート状細胞培養物は、シート状骨格筋芽細胞培養物である。これは、シート状骨格筋芽細胞培養物は、その一部をつかむと自重で破断するほど脆弱であるがゆえに、従来単体で移送することができないばかりか、一度折り重なると元の形状に戻すことが極めて困難なため、液中でシート形状を維持することに大きな意義があるからである。 In one embodiment of the present invention, the sheet-like cell culture is a sheet-like skeletal myoblast culture. This is because the sheet-like skeletal myoblast culture is so fragile that it breaks by its own weight when it is grabbed, so it cannot be transferred by itself, but once it is folded, it returns to its original shape. This is because it is extremely difficult to maintain the sheet shape in the liquid.
本明細書において、容器は、内部に脆弱物、液体などを収容でき、液体が漏出しないものであればとくに限定されず、市販の容器を含む任意のものを用いることができる。容器の材料としては、例えば、ポリエチレン、ポリプロピレン、テフロン(登録商標)、ポリエチレンテレフタレート、ポリメチルメタクリレート、ナイロン6,6、ポリビニルアルコール、セルロース、シリコン、ポリスチレン、ガラス、ポリアクリルアミド、ポリジメチルアクリルアミド、金属(例えば、鉄、ステンレス、アルミニウム、銅、真鍮)等が挙げられるがこれに限定されない。また、容器は、脆弱物の形状を維持するための少なくとも1つの平坦な底面を有することが好ましく、例えば、シャーレ、細胞培養皿、細胞培養ボトルなどが挙げられるがこれに限定されない。平坦な底面の面積は、特に限定されないが、典型的には、1.13〜78.5cm2、好ましくは12.6〜78.5cm2、より好ましくは9.1〜60.8cm2である。 In this specification, a container will not be specifically limited if a fragile substance, a liquid, etc. can be accommodated in the inside, and a liquid does not leak, Arbitrary things including a commercially available container can be used. Examples of the material of the container include polyethylene, polypropylene, Teflon (registered trademark), polyethylene terephthalate, polymethyl methacrylate, nylon 6,6, polyvinyl alcohol, cellulose, silicon, polystyrene, glass, polyacrylamide, polydimethylacrylamide, metal ( Examples thereof include, but are not limited to, iron, stainless steel, aluminum, copper, and brass. Moreover, it is preferable that a container has at least 1 flat bottom face for maintaining the shape of a fragile substance, for example, a petri dish, a cell culture dish, a cell culture bottle etc. are mentioned, However It is not limited to this. The area of the flat bottom surface is not particularly limited, but is typically 1.13 to 78.5 cm 2 , preferably 12.6 to 78.5 cm 2 , more preferably 9.1 to 60.8 cm 2 . .
本明細書において、容器内の液体は、少なくとも1種の成分から構成され、その成分としてはとくに限定されないが、例えば、水、水溶液、非水溶液、懸濁液、乳液などの液体から構成される。
本明細書における液または液体とは、全体として流動性を有する流体であればよく、細胞足場などの固形物質や気泡などその他非液体成分を含んでもよい。
In the present specification, the liquid in the container is composed of at least one component, and the component is not particularly limited. For example, the liquid is composed of liquid such as water, aqueous solution, non-aqueous solution, suspension, and emulsion. .
The liquid or liquid in the present specification may be a fluid having fluidity as a whole, and may include other non-liquid components such as solid substances such as cell scaffolds and bubbles.
容器内の液体を構成する成分は、脆弱物に与える影響が少ないものであればとくに限定されない。脆弱物が生体由来材料からなる膜である場合、容器内の液体を構成する成分は、生物学的安定性や長期保存可能性の観点から、生体適合性のもの、すなわち、生体組織や細胞に対して炎症反応、免疫反応、中毒反応などの望まない作用を起こさないか、少なくともかかる作用が小さいものが好ましく、例えば、水、生理食塩水、生理緩衝液(例えば、HBSS、PBS、EBSS、Hepes、重炭酸ナトリウム等)、培地(例えば、DMEM、MEM、F12、DMEM/F12、DME、RPMI1640、MCDB、L15、SkBM、RITC80−7、IMDM等)、糖液(スクロース溶液、Ficoll−paque(登録商標)PLUS等)、海水、血清含有溶液、レノグラフィン(登録商標)溶液、メトリザミド溶液、メグルミン溶液、グリセリン、エチレングリコール、アンモニア、ベンゼン、トルエン、アセトン、エチルアルコール、ベンゾール、オイル、ミネラルオイル、動物脂、植物油、オリーブ油、コロイド溶液、流動パラフィン、テレピン油、アマニ油、ヒマシ油などが挙げられる。 The components constituting the liquid in the container are not particularly limited as long as they have little influence on the fragile material. When the fragile material is a membrane made of a bio-derived material, the components constituting the liquid in the container are biocompatible from the viewpoint of biological stability and long-term storage, i.e., living tissue or cells. It is preferable that it does not cause an undesirable action such as an inflammatory reaction, an immune reaction, an toxic reaction, or at least a small such action. For example, water, physiological saline, physiological buffer (for example, HBSS, PBS, EBSS, Hepes) , Sodium bicarbonate, etc.), medium (for example, DMEM, MEM, F12, DMEM / F12, DME, RPMI1640, MCDB, L15, SkBM, RITC80-7, IMDM, etc.), sugar solution (sucrose solution, Ficoll-paque (registered) Trademark) PLUS), seawater, serum-containing solution, Renographin (registered trademark) solution, metrizamide solution, Meg Minine solution, glycerin, ethylene glycol, ammonia, benzene, toluene, acetone, ethyl alcohol, benzol, oil, mineral oil, animal fat, vegetable oil, olive oil, colloidal solution, liquid paraffin, turpentine oil, flaxseed oil, castor oil, etc. It is done.
脆弱物がシート状細胞培養物である場合、容器内の液体を構成する成分は、細胞を安定して保存することができ、細胞生存に必要な最低限の酸素や栄養等を含み、細胞を浸透圧等により破壊しないものが好ましく、例えば、生理食塩水、生理緩衝液(例えば、HBSS、PBS、EBSS、Hepes、重炭酸ナトリウム等)、培地(例えば、DMEM、MEM、F12、DMEM/F12、DME、RPMI1640、MCDB、L15、SkBM、RITC80−7、IMDM等)、糖液(スクロース溶液、Ficoll−paque PLUS(登録商標)等)などが挙げられるが、これらに限定されない。 When the fragile material is a sheet-like cell culture, the components constituting the liquid in the container can stably store the cells, contain the minimum oxygen and nutrients necessary for cell survival, Those that do not break due to osmotic pressure or the like are preferable. For example, physiological saline, physiological buffer (eg, HBSS, PBS, EBSS, Hepes, sodium bicarbonate, etc.), medium (eg, DMEM, MEM, F12, DMEM / F12, Examples thereof include, but are not limited to, DME, RPMI 1640, MCDB, L15, SkBM, RITC80-7, IMDM, and the like, sugar solutions (sucrose solution, Ficoll-paque PLUS (registered trademark), and the like).
本明細書において、蓋部材は、容器を密閉するものであればとくに限定されない。蓋部材の材料としては、例えば、ポリエチレン、ポリプロピレン、テフロン(登録商標)、ポリエチレンテレフタレート、ポリメチルメタクリレート、ナイロン6,6、ポリビニルアルコール、セルロース、シリコン、ポリスチレン、ガラス、ポリアクリルアミド、ポリジメチルアクリルアミド、金属(例えば、鉄、ステンレス、アルミニウム、銅、真鍮)等が挙げられるがこれに限定されない。 In the present specification, the lid member is not particularly limited as long as it seals the container. Examples of the material of the lid member include polyethylene, polypropylene, Teflon (registered trademark), polyethylene terephthalate, polymethyl methacrylate, nylon 6,6, polyvinyl alcohol, cellulose, silicon, polystyrene, glass, polyacrylamide, polydimethylacrylamide, and metal. (For example, iron, stainless steel, aluminum, copper, brass) and the like may be mentioned, but are not limited thereto.
本明細書において、容器は、有底筒状の形状を有する。筒状の水平断面の形状は、脆弱物の形状を維持するための少なくとも1つの平坦な底面が形成され得る限り、特に限定されないが、例えば、三角形、四角形、多角形、円形、楕円形などであり得る。蓋部材の形状は、蓋部材と容器とが係合可能で、かかる係合により密閉空間が形成され得る限り、特に限定されない。例えば、容器が汎用シャーレである場合は、蓋部材の形状を円形にすることが好ましい。また、蓋部材および/または容器を光透過性の材料で構成することで、容器に収容されている脆弱物の状態や、液体中の気泡の有無を確認できるようにしてもよい。 In the present specification, the container has a bottomed cylindrical shape. The shape of the cylindrical horizontal cross section is not particularly limited as long as at least one flat bottom surface for maintaining the shape of the fragile object can be formed, but for example, a triangle, a rectangle, a polygon, a circle, an ellipse, etc. possible. The shape of the lid member is not particularly limited as long as the lid member and the container can be engaged and a sealed space can be formed by the engagement. For example, when the container is a general-purpose petri dish, the shape of the lid member is preferably circular. Moreover, you may enable it to confirm the state of the weak substance accommodated in the container, and the presence or absence of the bubble in a liquid by comprising a cover member and / or a container with a light transmissive material.
本明細書において、容器の下部とは、液体、気体、脆弱物などを収容できる平坦な底面を有する容器の下側をいい、容器の上部とは、容器の上側、すなわち、容器の開口と下部との間をいう。また、容器の段差部とは、下部と上部との境界部分をいい、容器の内径が急減した部分、または、下部から上部にかけて内径が大きくなるテーパー部分をいい、下部と上部の内径の差分による幅を持つ環状の面を有している。そして、下部空間とは、容器の下部で取り囲まれる収容空間をいい、上部空間とは、容器の上部で取り囲まれる空間をいい、下部空間の開口とは、下部空間と段差部との境界の縁部を開口部とする開口をいい、上部空間の開口とは、容器の縁部、すなわち上部空間の縁部を開口部とする開口をいう。 In this specification, the lower part of the container refers to the lower side of the container having a flat bottom surface that can accommodate liquid, gas, fragile substances, etc., and the upper part of the container refers to the upper side of the container, that is, the opening and the lower part of the container. Between. The step part of the container refers to the boundary between the lower part and the upper part, the part where the inner diameter of the container suddenly decreases, or the tapered part where the inner diameter increases from the lower part to the upper part. It has an annular surface with a width. The lower space is the housing space surrounded by the lower part of the container, the upper space is the space surrounded by the upper part of the container, and the opening of the lower space is the edge of the boundary between the lower space and the stepped part. The opening of the upper space is an opening having the edge of the container, that is, the edge of the upper space as the opening.
本明細書において、拡張部材とは、収縮形態と、該収縮形態よりも拡張して容器と密着する拡張形態とに移行可能な部材をいう。拡張部材は、蓋部材と容器との間に介在することができ、拡張部材を収縮形態から拡張形態へ移行させることで脆弱物および液体を収容した容器内空間の気体および液体を押し出して、容器と密着させることで液密空間を形成することができる。すなわち、拡張部材が収縮形態から拡張形態に移行する間、つまり拡張部材が、容器と密着するまでは、拡張部材と容器との間に空間ができるため、この空間を排出経路として利用して、容器内から押し出された気体および液体を排出することができる。拡張部材は、蓋部材の一部であっても、蓋部材と別体であってもよい。拡張部材の形状は、拡張形態において容器の内面に密着可能であれば、特に限定されない。 In this specification, the expansion member refers to a member that can be shifted to a contracted form and an expanded form that expands more than the contracted form and comes into close contact with the container. The expansion member can be interposed between the lid member and the container, and by moving the expansion member from the contracted form to the expanded form, the gas and liquid in the container internal space containing the fragile material and liquid are pushed out, and the container A liquid-tight space can be formed by closely contacting. That is, while the expansion member transitions from the contracted form to the expanded form, that is, until the expansion member comes into close contact with the container, a space is created between the expansion member and the container. The gas and liquid pushed out from inside the container can be discharged. The expansion member may be a part of the lid member or may be separate from the lid member. The shape of the expansion member is not particularly limited as long as it can be in close contact with the inner surface of the container in the expanded configuration.
本明細書において、凸部とは、例えば、突き出ている部分、膨らんでいる部分など、すなわち、平坦ではない部分をいう。下部空間に向けて突出する凸部とは、凸部が容器の下部空間内の液体や気体を押し出すことができる程度に突出していることをいい、当業者は、容器の容積、使用する液体の量や液嵩に応じて、凸部の大きさを自由に設定することができる。 In this specification, the convex portion refers to, for example, a protruding portion, a bulging portion, or the like, that is, a portion that is not flat. The convex portion protruding toward the lower space means that the convex portion protrudes to such an extent that the liquid or gas in the lower space of the container can be pushed out. The size of the convex portion can be freely set according to the amount and the liquid volume.
本明細書において、容器内空間とは、液体、気体、脆弱物などを収容できる平坦な面を有する容器の収容空間をいう。したがって、容器内空間に向けて突出する凸部とは、容器内空間の気体や液体が凸部の容積分だけ押し出されることを意味する。さらに、容器の縁部とは、容器内空間を構成する容器の縁部をいう。 In this specification, the container internal space refers to a container storage space having a flat surface that can store liquid, gas, fragile material, and the like. Therefore, the convex portion protruding toward the inner space of the container means that the gas or liquid in the inner space of the container is pushed out by the volume of the convex portion. Furthermore, the edge part of a container means the edge part of the container which comprises the space in a container.
本明細書において、凸部の水平断面積とは、例えば、凸部を液体に浸漬した状態で、凸部を液面で切断したときに現れる2次元断面の面積をいう。したがって、凸部の水平断面積が垂直下方に向かうほど小さいとは、凸部を液体の上方から垂直下方に降下させながら液体に浸漬する場合、凸部と液体との接触面積が徐々に大きくなることをいう。 In this specification, the horizontal cross-sectional area of a convex part means the area of the two-dimensional cross section which appears when a convex part is cut | disconnected by the liquid level in the state which immersed the convex part in the liquid, for example. Therefore, the horizontal cross-sectional area of the convex portion is so small that it goes vertically downward. When the convex portion is immersed in the liquid while descending vertically from the top of the liquid, the contact area between the convex portion and the liquid gradually increases. That means.
本発明の一態様において、凸部は、頂部を有するドーム形状であり、好ましくは、凸部の頂部と、蓋部材の中心線および容器の中心線とが交わるように設計される。凸部の曲面の形状としては、双曲面形状、放物面形状、半球面形状、円錐面形状、角錐面形状などが挙げられるが、これに限定されない。 In one aspect of the present invention, the convex portion has a dome shape having a top portion, and is preferably designed so that the top portion of the convex portion intersects the center line of the lid member and the center line of the container. Examples of the curved shape of the convex portion include, but are not limited to, a hyperboloid shape, a paraboloid shape, a hemispherical shape, a conical surface shape, and a pyramidal surface shape.
本明細書において、脆弱物は液体が収容された容器内の液体中に保持される。脆弱物の液体中での位置は、特に限定されないが、蓋部材を容器に取り付けて密閉空間を形成した状態で、蓋部材(または拡張部材)と脆弱物とが接触しない位置に配置される(または接触してもよい)。好ましくは、脆弱物は、容器の液体中で、容器の底面上、底面付近などに配置される。 In this specification, the fragile substance is held in a liquid in a container in which the liquid is stored. The position of the fragile material in the liquid is not particularly limited, but is arranged at a position where the lid member (or the expansion member) and the fragile material do not come into contact with the lid member attached to the container to form a sealed space ( Or you may touch. Preferably, the fragile substance is disposed on the bottom surface of the container, in the vicinity of the bottom surface, or the like in the liquid of the container.
以下、本発明の好適な実施形態について、図面を参照しつつ詳細に説明する。
〔第1実施形態〕
まず、本発明の第1実施形態について説明する。
図1は、本発明の第1実施形態に係るデバイスの断面図、図2は、第1実施形態の第1変形例に係るデバイスの断面図、図3は、第1実施形態の第2変形例に係るデバイスの断面図、図4は、第1実施形態の第3変形例に係るデバイスの断面図である。なお、本願における各図において、説明を容易とするため、各部材の大きさは、適宜強調されており、図示の各部材は、実際の大きさを示すものではない。
DESCRIPTION OF EXEMPLARY EMBODIMENTS Hereinafter, preferred embodiments of the invention will be described in detail with reference to the drawings.
[First Embodiment]
First, a first embodiment of the present invention will be described.
1 is a cross-sectional view of a device according to the first embodiment of the present invention, FIG. 2 is a cross-sectional view of a device according to a first modification of the first embodiment, and FIG. 3 is a second modification of the first embodiment. Sectional drawing of the device which concerns on an example, FIG. 4 is sectional drawing of the device which concerns on the 3rd modification of 1st Embodiment. In each drawing in the present application, for ease of explanation, the size of each member is emphasized as appropriate, and the illustrated members do not indicate actual sizes.
図1Aに示すように、本発明の第1実施形態に係るデバイス1は、容器2および容器2を密閉する蓋部材3を含む。容器2は、縁部25を有する汎用シャーレであり、脆弱物Sなどを収容できる容器内空間を構成する。蓋部材3は、容器2の縁部25と密着して容器2内を密閉することができる天板部36と、天板部36の周縁から垂下する筒状スカート壁37と、筒状スカート壁37の内面に突設される係合部33とを含む。蓋部材3は、さらに拡張部材32と、拡張部材32に給排気を行うための給排気弁Vを含み、拡張部材32は、底面34、外周面35を含む。 As shown in FIG. 1A, the device 1 according to the first embodiment of the present invention includes a container 2 and a lid member 3 that seals the container 2. The container 2 is a general-purpose petri dish having an edge 25 and constitutes a container internal space that can accommodate the fragile material S and the like. The lid member 3 is in close contact with the edge 25 of the container 2 to seal the inside of the container 2, a cylindrical skirt wall 37 that hangs down from the periphery of the top plate 36, and a cylindrical skirt wall 37 and an engaging portion 33 projecting from the inner surface of 37. The lid member 3 further includes an expansion member 32 and a supply / exhaust valve V for supplying and exhausting the expansion member 32, and the expansion member 32 includes a bottom surface 34 and an outer peripheral surface 35.
図1Bに示すように、デバイス1を使用する際は、容器2に液体Lを注ぎ入れて脆弱物Sを収容し、容器2に蓋部材3を被せる。次に、収縮形態の拡張部材32に給排気弁Vから空気を給気して拡張部材32を拡張させる。拡張部材32が液面に達した後、さらに拡張部材32を拡張させると、容器内の気体と液体Lは拡張部材32の外周面35と容器2の内周面との間の空間に押し出され、天板部36と縁部25との間を通って外に押し出される。したがって、拡張部材32と容器2との間、および天板部36と縁部25との間が、容器2内の気体および液体Lの排出経路となる。 As shown in FIG. 1B, when using the device 1, the liquid L is poured into the container 2 to contain the fragile material S, and the container 2 is covered with the lid member 3. Next, the expansion member 32 is expanded by supplying air from the supply / exhaust valve V to the expansion member 32 in the contracted form. When the expansion member 32 is further expanded after the expansion member 32 reaches the liquid level, the gas and the liquid L in the container are pushed into the space between the outer peripheral surface 35 of the expansion member 32 and the inner peripheral surface of the container 2. Then, it is pushed out through the space between the top plate portion 36 and the edge portion 25. Therefore, the space between the expansion member 32 and the container 2 and the space between the top plate portion 36 and the edge portion 25 serve as a discharge path for the gas and liquid L in the container 2.
また、さらに拡張部材32を拡張させて拡張形態にすると、拡張部材32の外周面35と、容器2の内周面とが密着し、拡張部材32の底面34と、容器2の内面とで囲まれる液密空間が形成される。液密空間を形成した後、蓋部材3の天板部36を容器2の縁部25に対して押し付け、蓋部材3の係合部33を容器2に係合させて容器2を密閉し、デバイス1を移送する。このように、拡張部材32は、拡張部材32による液密空間の形成の後に、蓋部材3による密閉空間の形成を行うことができる拡張機構として機能する。脆弱物Sを使用する際は、蓋部材3の係合を解除して、天板部36と縁部25との密着を解除し、拡張部材32の給排気弁Vから空気を排気して、拡張部材32を収縮形態に移行させ、蓋部材3を容器2から取り外して、脆弱物Sを取り出す。 Further, when the expansion member 32 is further expanded to an expanded form, the outer peripheral surface 35 of the expansion member 32 and the inner peripheral surface of the container 2 are in close contact with each other, and are surrounded by the bottom surface 34 of the expansion member 32 and the inner surface of the container 2. A liquid-tight space is formed. After forming the liquid-tight space, the top plate portion 36 of the lid member 3 is pressed against the edge 25 of the container 2, the engaging portion 33 of the lid member 3 is engaged with the container 2, and the container 2 is sealed, Device 1 is transported. As described above, the expansion member 32 functions as an expansion mechanism that can form the sealed space by the lid member 3 after the liquid-tight space is formed by the expansion member 32. When using the fragile material S, the engagement of the lid member 3 is released, the close contact between the top plate portion 36 and the edge portion 25 is released, air is exhausted from the supply / exhaust valve V of the expansion member 32, The expansion member 32 is shifted to the contracted form, the lid member 3 is removed from the container 2, and the fragile material S is taken out.
本実施形態はこれに限定されるものではなく、当業者は、異なる構成や形状を有するデバイスを設計することができる。例えば、蓋部材3および/または容器2に、容器2内の気体および液体Lの排出経路となる排出口を設けて、かかる排出口を開閉しながら、液密空間や気密空間を形成するようにしてもよい。この場合は、蓋部材3を容器2に取り付けた状態で、拡張部材32の拡張を行ってもよい。また、例えば、容器2の外周面に、蓋部材3の係合部27と係合する溝を上側と下側の2カ所に設けて、2段階で係合できるようにしてもよい。これにより、1段階目の係合で、蓋部材3の容器2に対する位置決め、すなわち、拡張部材32の容器2に対する位置決めを行い、2段階目の係合で、容器2を密閉できるようにしてもよい。このように、拡張部材32は、拡張部材32による液密空間の形成の後に、蓋部材3による密閉空間の形成を行うことができる。 This embodiment is not limited to this, and those skilled in the art can design devices having different configurations and shapes. For example, the lid member 3 and / or the container 2 is provided with a discharge port serving as a discharge path for the gas and liquid L in the container 2, and a liquid-tight space and an air-tight space are formed while opening and closing the discharge port. May be. In this case, the expansion member 32 may be expanded with the lid member 3 attached to the container 2. Further, for example, grooves that engage with the engaging portion 27 of the lid member 3 may be provided on the outer peripheral surface of the container 2 at two locations, the upper side and the lower side, so that the engagement can be performed in two stages. As a result, the lid member 3 is positioned with respect to the container 2 by the first-stage engagement, that is, the expansion member 32 is positioned with respect to the container 2, and the container 2 can be sealed by the second-stage engagement. Good. Thus, the expansion member 32 can form the sealed space by the lid member 3 after the liquid-tight space is formed by the expansion member 32.
以上、本発明の第1実施形態に係るデバイス1によれば、容器内を確実に液密空間にできるため、泡(気体)が容器内に入らず、容器の揺れによって泡が容器内で動いて脆弱物を破損することがない。特に、脆弱物がシート状細胞培養物の積層体である場合に、気泡が移動して、積層体がズレたり欠損したりすることがない。また、製造段階で容器や蓋の寸法にズレが生じても、確実に容器内を液密にすることができるため、設計コストや製造コストの点において大きなメリットがある。 As mentioned above, according to the device 1 which concerns on 1st Embodiment of this invention, since the inside of a container can be made into a liquid-tight space reliably, a bubble (gas) does not enter in a container, but a bubble moves in a container by the shaking of a container. And will not damage fragile materials. In particular, when the fragile material is a laminated body of sheet-like cell cultures, bubbles do not move and the laminated body is not displaced or lost. In addition, even if the container or the lid is displaced in the manufacturing stage, the inside of the container can be surely liquid-tight, which is a great merit in terms of design cost and manufacturing cost.
次に、本発明の第1実施形態に係るデバイス1の第1変形例について説明する。以下、第1実施形態との相違点について詳細に説明し、同様の事項については、説明を省略する。 Next, a first modification of the device 1 according to the first embodiment of the present invention will be described. Hereinafter, differences from the first embodiment will be described in detail, and description of similar matters will be omitted.
図2Aに示すように、第1変形例に係るデバイス1Aは、容器2Aおよび容器2Aを密閉する蓋部材3Aを含む。本変形例において、容器2Aは、上部22および下部23を含む有底筒状の容器であり、下部23は、脆弱物Sなどを収容できる容器内空間を構成する。上部22の内径は下部23の内径より大きく、上部22と下部23との境界に段差部24が設けられている。容器2Aの上部22外周の下端部と上端部との間には係合部27が設けられており、蓋部材3Aの係合部33と係合できるようになっている。 As shown in FIG. 2A, the device 1A according to the first modification includes a container 2A and a lid member 3A that seals the container 2A. In this modification, the container 2A is a bottomed cylindrical container including an upper part 22 and a lower part 23, and the lower part 23 constitutes a container inner space in which the fragile material S and the like can be accommodated. The inner diameter of the upper part 22 is larger than the inner diameter of the lower part 23, and a step part 24 is provided at the boundary between the upper part 22 and the lower part 23. An engaging portion 27 is provided between the lower end portion and the upper end portion of the outer periphery of the upper portion 22 of the container 2A so that it can engage with the engaging portion 33 of the lid member 3A.
図2Bに示すように、デバイス1Aを使用する際は、容器2Aに液体Lを注ぎ入れて、容器2Aの下部23に脆弱物Sを収容する。そして、容器2Aに蓋部材3Aを被せて、蓋部材3Aの係合部33と、容器2Aの外周に設けられた係合部27とを係合させて、蓋部材3Aの容器2Aに対する位置決め、すなわち、拡張部材32の容器2Aに対する位置決めを行う。この際、係合部33を上部22の下端部までは係合させず、容器2Aの天板部36と容器2Aの縁部25とを密着させずに排出経路を確保しておく。 As shown in FIG. 2B, when using the device 1A, the liquid L is poured into the container 2A, and the fragile material S is accommodated in the lower portion 23 of the container 2A. Then, the lid member 3A is placed on the container 2A, and the engaging portion 33 of the lid member 3A is engaged with the engaging portion 27 provided on the outer periphery of the container 2A, so that the positioning of the lid member 3A with respect to the container 2A is performed. That is, the expansion member 32 is positioned with respect to the container 2A. At this time, the engaging portion 33 is not engaged to the lower end portion of the upper portion 22, and the discharge path is secured without bringing the top plate portion 36 of the container 2A and the edge portion 25 of the container 2A into close contact.
次に、拡張部材32を拡張形態に移行させ、拡張部材32が液面に達した後、さらに拡張部材32を進入させると、液体Lは拡張部材32の外周面35と容器2Aの内周面との間の空間に押し出されて液面が上昇する。液面が上昇すると、容器2A内の空気Aが押されて、容器2Aの上部開口部25から外に排出される。この時点では天板部36と上部開口部25との密着が起こっていないため、液体Lおよび空気Aが移動することができる。そして、さらに拡張部材32を拡張させると、拡張部材32の底面34と段差部24との密着が起こり、収容空間(下部23空間)内に液密空間が形成される。 Next, when the expansion member 32 is shifted to the expanded form, and the expansion member 32 reaches the liquid level, and the expansion member 32 is further moved in, the liquid L is in the outer peripheral surface 35 of the expansion member 32 and the inner peripheral surface of the container 2A. The liquid level rises by being pushed into the space between the two. When the liquid level rises, the air A in the container 2A is pushed and discharged outside from the upper opening 25 of the container 2A. At this time, since the close contact between the top plate portion 36 and the upper opening 25 has not occurred, the liquid L and the air A can move. When the expansion member 32 is further expanded, the bottom surface 34 of the expansion member 32 and the stepped portion 24 come into close contact with each other, and a liquid-tight space is formed in the accommodation space (lower 23 space).
本変形例においては、拡張部材32は、拡張形態において、その底面34は容器2Aの段差部24とは密着するが、その外周面35は容器2Aの上部22内周面とは密着しない。すなわち、拡張形態において、拡張部材32の外径が、下部23の内径より大きく、かつ上部22の内径より小さく、そして、拡張部材32の高さが、容器2Aの上部22の高さより僅かに大きくなるように構成されている。これにより、押し出された液体が、外周面35と上部22との間の液体受容空間に受容されるため、周囲を汚染することがない上に、液密空間を確実に形成した後に、蓋部材3Aで容器2Aを密閉することができる。 In this modification, in the expanded form, the expansion member 32 has its bottom surface 34 in close contact with the stepped portion 24 of the container 2A, but its outer peripheral surface 35 is not in close contact with the inner peripheral surface of the upper portion 22 of the container 2A. That is, in the expanded form, the outer diameter of the expansion member 32 is larger than the inner diameter of the lower portion 23 and smaller than the inner diameter of the upper portion 22, and the height of the expansion member 32 is slightly larger than the height of the upper portion 22 of the container 2A. It is comprised so that it may become. Thus, the extruded liquid is received in the liquid receiving space between the outer peripheral surface 35 and the upper portion 22, so that the surroundings are not contaminated, and the lid member is formed after the liquid-tight space is reliably formed. The container 2A can be sealed with 3A.
液密空間を形成した後、蓋部材3Aの天板部36を容器2Aの上部開口部25に対して押し付け、蓋部材3Aの係合部33を容器2Aの上部22の下端部に係合させて容器2Aを密閉し、デバイス1Aを移送する。脆弱物Sを使用する際は、蓋部材3Aの係合を解除して、天板部36と上部開口部25との密着を解除し、拡張部材32の給排気弁Vから空気を排気して、拡張部材32を収縮形態に移行させ、蓋部材3Aを容器2Aから取り外して、脆弱物Sを取り出す。 After forming the liquid-tight space, the top plate portion 36 of the lid member 3A is pressed against the upper opening 25 of the container 2A, and the engaging portion 33 of the lid member 3A is engaged with the lower end portion of the upper portion 22 of the container 2A. The container 2A is sealed and the device 1A is transferred. When using the fragile material S, the engagement of the lid member 3A is released, the close contact between the top plate portion 36 and the upper opening 25 is released, and air is exhausted from the supply / exhaust valve V of the expansion member 32. Then, the expansion member 32 is shifted to the contracted form, the lid member 3A is removed from the container 2A, and the fragile material S is taken out.
以上、本発明の第1実施形態に係るデバイス1の第1変形例によれば、容器内を確実に液密空間にできるため、泡(気体)が容器内に入らず、容器の揺れによって泡が容器内で動いて脆弱物を破損することがない。特に、脆弱物がシート状細胞培養物の積層体である場合に、気泡が移動して、積層体がズレたり欠損したりすることがない。また、製造段階で容器や蓋の寸法にズレが生じても、確実に容器内を液密にすることができるため、設計コストや製造コストの点において大きなメリットがある。 As mentioned above, according to the 1st modification of the device 1 which concerns on 1st Embodiment of this invention, since the inside of a container can be made into a liquid-tight space reliably, a bubble (gas) does not enter into a container but a bubble is caused by the shaking of a container. Will not move in the container and damage fragile materials. In particular, when the fragile material is a laminated body of sheet-like cell cultures, bubbles do not move and the laminated body is not displaced or lost. In addition, even if the container or the lid is displaced in the manufacturing stage, the inside of the container can be surely liquid-tight, which is a great merit in terms of design cost and manufacturing cost.
次に、本発明の第1実施形態に係るデバイス1の第2変形例について説明する。以下、第1実施形態との相違点について詳細に説明し、同様の事項については、説明を省略する。 Next, a second modification of the device 1 according to the first embodiment of the present invention will be described. Hereinafter, differences from the first embodiment will be described in detail, and description of similar matters will be omitted.
図3Aに示すように、第2変形例に係るデバイス1Bは、容器2Bおよび容器2Bを密閉する蓋部材3Bを含む。本変形例において、容器2Bは、上部22および下部23を含む有底筒状の容器であり、下部23は、脆弱物Sなどを収容できる容器内空間を構成する。上部22の内径は下部23の内径より大きく、上部22と下部23との境界に段差部24が設けられている。 As illustrated in FIG. 3A, a device 1B according to the second modification includes a container 2B and a lid member 3B that seals the container 2B. In this modification, the container 2B is a bottomed cylindrical container including an upper part 22 and a lower part 23, and the lower part 23 constitutes a container inner space in which the fragile material S and the like can be accommodated. The inner diameter of the upper part 22 is larger than the inner diameter of the lower part 23, and a step part 24 is provided at the boundary between the upper part 22 and the lower part 23.
筒状スカート壁37の内周面には、雌ネジ部38が設けられており、容器2Bの上部22の外周面に設けられている雄ネジ部28と螺合できるようになっている。拡張部材32は、拡張形態において下部23内空間に向けて突出する凸部31を含む。凸部31の形状は、頂部を有する円形のドーム形状である。すなわち、凸部31の水平断面積は円形で、垂直下方に向かうほど小さく、凸部31の曲面は放物面形状を有する。 A female screw portion 38 is provided on the inner peripheral surface of the cylindrical skirt wall 37 so that it can be screwed with a male screw portion 28 provided on the outer peripheral surface of the upper portion 22 of the container 2B. The expansion member 32 includes a convex portion 31 that protrudes toward the inner space of the lower portion 23 in the expanded configuration. The shape of the convex portion 31 is a circular dome shape having a top portion. That is, the horizontal cross-sectional area of the convex portion 31 is circular and decreases toward the vertically lower side, and the curved surface of the convex portion 31 has a parabolic shape.
図3Bに示すように、デバイス1Bを使用する際は、容器2Bに液体Lを注ぎ入れて、容器2Bの下部23に脆弱物Sを収容する。そして、容器2Bに蓋部材3Bを被せて、蓋部材3Bの雌ネジ部38の下端部と、容器2Bの雄ネジ部28の上端部とを螺合させて、蓋部材3Bの容器2Bに対する位置決め、すなわち、拡張部材32の容器2Bに対する位置決めを行う。この際、雌ネジ部38の下端部を雄ネジ部28の下端部までは螺合させず、容器2Bの天板部36と容器2Bの縁部25とを密着させずに排出経路を確保しておく。 As shown in FIG. 3B, when using the device 1B, the liquid L is poured into the container 2B, and the fragile material S is accommodated in the lower part 23 of the container 2B. Then, the lid member 3B is placed on the container 2B, and the lower end portion of the female screw portion 38 of the lid member 3B and the upper end portion of the male screw portion 28 of the container 2B are screwed together to position the lid member 3B with respect to the container 2B. That is, the expansion member 32 is positioned with respect to the container 2B. At this time, the lower end portion of the female screw portion 38 is not screwed to the lower end portion of the male screw portion 28, and the discharge path is ensured without closely contacting the top plate portion 36 of the container 2B and the edge portion 25 of the container 2B. Keep it.
次に、拡張部材32を拡張形態に移行させ、凸部31が下部23内空間に向けて拡張すると、先ず容器内空間の気体が容器外空間へ押し出され、気体がすべて押し出されると、次に液体Lが押し出される。拡張部材32と容器2Bの下部開口部26との密着は、気体がすべて押し出された後に起こるように、事前に液量を調節するか、凸部31の高さを調節するなどして、液密空間が確実に形成されるようにする。また、本変形例において、拡張部材32の外周面35は、拡張形態において容器2Bの上部22の内周面と密着しないように構成されている。したがって、容器内空間から押し出された液体Lは、容器2Bの上部22と拡張部材32の外周面35との間の受容空間に受容され、外に流出することがない。また、本変形例において、拡張部材32は拡張状態で楕円体のバルーン形状を有し、図示されるように拡張部材32と天板部36との間にも受容空間を有するため、容器内の液量が多い場合であっても、押し出された液体Lを受容することができる。 Next, when the expansion member 32 is shifted to the expanded form and the convex portion 31 expands toward the inner space of the lower portion 23, first, the gas in the inner space of the container is pushed out to the outer space of the container, and then all the gas is pushed out. Liquid L is extruded. The close contact between the expansion member 32 and the lower opening 26 of the container 2B is adjusted by adjusting the amount of liquid in advance or by adjusting the height of the convex portion 31 so that the gas is completely pushed out. Ensure that a tight space is formed. Moreover, in this modification, the outer peripheral surface 35 of the expansion member 32 is configured not to be in close contact with the inner peripheral surface of the upper portion 22 of the container 2B in the expanded configuration. Therefore, the liquid L pushed out from the inner space of the container is received in the receiving space between the upper part 22 of the container 2B and the outer peripheral surface 35 of the expansion member 32, and does not flow out. Further, in this modification, the expansion member 32 has an elliptical balloon shape in the expanded state, and has a receiving space between the expansion member 32 and the top plate portion 36 as shown in the figure. Even when the amount of liquid is large, the extruded liquid L can be received.
容器2Bの下部開口部26と密着する拡張部材32の密着部分(この場合、凸部31)は、容器2Bの水平面に対して傾斜しているため、気体に浮力が掛りやすく、液体中の気泡などを確実に押し出すことができる。また、かかる傾斜により、拡張部材32を容器2Aの下部23空間内に拡張する際に、拡張部材32の外面と下部23の内面との距離が徐々に小さくなるため、液体Lを容器外空間へ緩やかに押し出すことができ、下部23内の液体Lの流動を抑えることができる。 Since the close contact portion (in this case, the convex portion 31) of the expansion member 32 that is in close contact with the lower opening 26 of the container 2B is inclined with respect to the horizontal plane of the container 2B, buoyancy tends to be applied to the gas, and bubbles in the liquid Etc. can be pushed out reliably. In addition, when the expansion member 32 is expanded into the lower space 23 of the container 2A due to such an inclination, the distance between the outer surface of the expansion member 32 and the inner surface of the lower portion 23 is gradually reduced. The liquid L can be gently pushed out, and the flow of the liquid L in the lower portion 23 can be suppressed.
また、凸部31の形状が頂部を有するドーム形状であるため、凸部31を液体Lに浸漬する際に、面積の小さな頂部が最初に液面に接触し、それから徐々に接触面積が大きくなるため、容器2B内の液体Lの波打ちを最小限に抑えることができる。また、凸部31のドーム形状が円形であるため、液体Lは円形ドームに沿って放射状に均一に押し出される。したがって、容器2B内の液体Lが半径方向の偏った方向に移動することがなく、結果的に、容器2B内の液体Lの流動を抑えることができる。 Moreover, since the shape of the convex part 31 is a dome shape having a top part, when the convex part 31 is immersed in the liquid L, the small top part first comes into contact with the liquid surface, and then the contact area gradually increases. Therefore, the undulation of the liquid L in the container 2B can be minimized. Moreover, since the dome shape of the convex part 31 is circular, the liquid L is uniformly extruded radially along the circular dome. Therefore, the liquid L in the container 2B does not move in the radial direction, and as a result, the flow of the liquid L in the container 2B can be suppressed.
液密空間を形成した後、雌ネジ部38の下端部を雄ネジ部28の下端部まで螺合させて、蓋部材3Bを容器2Bに対して螺着させて密閉し、デバイス1Bを移送する。脆弱物Sを使用する際は、蓋部材3Bの螺着を解除して、天板部36と縁部25との密着を解除し、拡張部材32の給排気弁Vから空気を排気して、拡張部材32を収縮形態に移行させ、蓋部材3Bを容器2Bから取り外して、脆弱物Sを取り出す。 After forming the liquid-tight space, the lower end portion of the female screw portion 38 is screwed to the lower end portion of the male screw portion 28, the lid member 3B is screwed onto the container 2B, and the device 1B is transferred. . When using the fragile material S, the screwing of the lid member 3B is released, the close contact between the top plate portion 36 and the edge portion 25 is released, the air is exhausted from the supply / exhaust valve V of the expansion member 32, The expansion member 32 is shifted to the contracted form, the lid member 3B is removed from the container 2B, and the fragile material S is taken out.
以上、本発明の第1実施形態に係るデバイス1の第2変形例によれば、容器内を確実に液密空間にできるため、泡(気体)が容器内に入らず、容器の揺れによって泡が容器内で動いて脆弱物を破損することがない。特に、脆弱物がシート状細胞培養物の積層体である場合に、気泡が移動して、積層体がズレたり欠損したりすることがない。また、製造段階で容器や蓋の寸法にズレが生じても、確実に容器内を液密にすることができるため、設計コストや製造コストの点において大きなメリットがある。 As mentioned above, according to the 2nd modification of the device 1 which concerns on 1st Embodiment of this invention, since the inside of a container can be made into a liquid-tight space reliably, a bubble (gas) does not enter in a container, but a bubble is caused by the shaking of a container. Will not move in the container and damage fragile materials. In particular, when the fragile material is a laminated body of sheet-like cell cultures, bubbles do not move and the laminated body is not displaced or lost. In addition, even if the container or the lid is displaced in the manufacturing stage, the inside of the container can be surely liquid-tight, which is a great merit in terms of design cost and manufacturing cost.
本実施形態はこれに限定されるものではなく、当業者は、上記の第1実施形態に係るデバイス1、第1変形例に係るデバイス1A、および第2変形例に係るデバイス1Bの構成および形状を好適に組み合わせて、異なる構成や形状を有するデバイスを設計することができる。例えば、図4に示される第3変形例のように、第1実施形態に係るデバイス1の拡張部材32の形状を、第2変形例に係るデバイス1Bの拡張部材32のように、拡張状態において楕円体のバルーン形状を有するように構成してもよい。これにより、拡張部材32を拡張して、拡張部材32の外周面35が容器2の内面と密着した際に、押し出された液体Lを拡張部材32と天板部36との間の受容空間で受容することで、液体Lが容器外に流出しないようにすることもできる。 This embodiment is not limited to this, and those skilled in the art will understand the configuration and shape of the device 1 according to the first embodiment, the device 1A according to the first modification, and the device 1B according to the second modification. Devices having different configurations and shapes can be designed by suitably combining the above. For example, as in the third modification shown in FIG. 4, the shape of the expansion member 32 of the device 1 according to the first embodiment is set in the expanded state like the expansion member 32 of the device 1B according to the second modification. You may comprise so that it may have an ellipsoidal balloon shape. Thereby, when the expansion member 32 is expanded and the outer peripheral surface 35 of the expansion member 32 comes into close contact with the inner surface of the container 2, the pushed liquid L is received in the receiving space between the expansion member 32 and the top plate portion 36. By receiving the liquid L, it is possible to prevent the liquid L from flowing out of the container.
以上、本発明を図示の実施形態について説明したが、本発明はこれに限定されるものではない。例えば、容器の段差部に凹部を設けて、かかる凹部に容器から押し出された液体が保持されるように構成してもよい。これにより、拡張部材を収縮形態に移行させた場合であっても、凹部内に保持されている液体が容器に戻ることがないため、容器内の液体の流動が起こりにくいだけでなく、脆弱物の汚染を防ぐことができる。また、蓋部材と容器の縁部との間にパッキンリングを介在させて、密閉性を高めるように構成してもよい。
本発明においては、各構成は、同様の機能を発揮し得る任意のものと置換することができ、あるいは、任意の構成を付加することもできる。
Although the present invention has been described with reference to the illustrated embodiment, the present invention is not limited to this. For example, a recess may be provided in the step portion of the container, and the liquid pushed out from the container may be held in the recess. Thereby, even when the expansion member is moved to the contracted form, the liquid held in the recess does not return to the container, so that the liquid in the container does not easily flow and is not fragile. Can prevent pollution. Moreover, you may comprise so that a sealing ring may be improved by interposing a packing ring between the cover member and the edge of a container.
In the present invention, each component can be replaced with any component that can exhibit the same function, or any component can be added.
1、1A、1B デバイス
2、2A、2B 容器
22 上部
23 下部
24 段差部
25 縁部、上部開口部
26 下部開口部
27 係合部
28 雄ネジ部
1, 1A, 1B Device 2, 2A, 2B Container 22 Upper part 23 Lower part 24 Step part 25 Edge part, Upper opening part 26 Lower opening part 27 Engagement part 28 Male thread part
3、3A、3B 蓋部材
31 凸部
32 拡張部材
33 係合部
34 底面
35 外周面
36 天板部
37 筒状スカート壁
38 雌ネジ部
3, 3A, 3B Lid member 31 Convex part 32 Expansion member 33 Engagement part 34 Bottom face 35 Outer peripheral face 36 Top plate part 37 Cylindrical skirt wall 38 Female thread part
Claims (8)
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JP2017141180A JP2019017344A (en) | 2017-07-20 | 2017-07-20 | Fragile product holding device equipped with expansion mechanism |
Applications Claiming Priority (1)
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JP2017141180A JP2019017344A (en) | 2017-07-20 | 2017-07-20 | Fragile product holding device equipped with expansion mechanism |
Publications (1)
Publication Number | Publication Date |
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JP2019017344A true JP2019017344A (en) | 2019-02-07 |
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