TWI323743B - Apparatus for cell culture and method for culturing cells - Google Patents

Apparatus for cell culture and method for culturing cells Download PDF

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Publication number
TWI323743B
TWI323743B TW092137188A TW92137188A TWI323743B TW I323743 B TWI323743 B TW I323743B TW 092137188 A TW092137188 A TW 092137188A TW 92137188 A TW92137188 A TW 92137188A TW I323743 B TWI323743 B TW I323743B
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Taiwan
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culture
plate
top plate
fluid
cell
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TW092137188A
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TW200521225A (en
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Wen Tyng Li
yu shi Weng
Ming Zheng Shiu
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Ind Tech Res Inst
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Priority to US11/019,380 priority patent/US7029907B2/en
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/16—Microfluidic devices; Capillary tubes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/12—Well or multiwell plates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/22—Transparent or translucent parts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/14—Scaffolds; Matrices
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability

Description

1323743 玫、發明說明： 【發明所屬之技術領域】 本發明係關於一種細胞培養裝置與體外培養細胞的 方法，尤指一種適用於醫療級細胞增生、藥物篩選或自動 5 化細胞分析之組織工程技術。 【先前技術】 在未來的組織工程領域中，細胞移植將扮演—重要的 角色，而目前的細胞擴大培養裝置，不論是傳統的實驗室 10細胞培養技術，或是傳統生物反應器，對於未來用以培養 醫療級的細胞來源都有其侷限性，前者最大的弊病在於其 缺乏質傳系統而難以呈現細胞於體内的真實活性；後者則 只適用於蛋白質藥物，例如一般耐受性較佳的間質細胞 (stromal cells)或纖維母細胞（fibr〇blast)的量產，而且其體 15積大、操作不便，系統中極大流體剪力與缺乏類似生理模 式下的微環境，對於具生物功能的組織專屬（tissue specific 細胞（如肝細胞），幾乎無法進行培養。此外，在量產個人 用細胞時，傳統系統中所需付出的龐大成本，將難進行個 人化細胞醫療的產業化。 20 美國MIT大學與麻州醫院曾於w〇 9947922號專利中 揭露一種包含微陣歹Umocromatrix)和灌注單元、以及感應 裝置的系統設計，其主要係用於藥物篩選與檢測，其雖可 於體外維持細胞功能’但細胞會形成團塊，難以分離與增 生。另外，美國UCSD大學於美國專利公開號第 6

Claims (1)

1323743 公告本 拾、申請#利範圍 L —種細胞培養裝置，係配合一流體，包括^ —具有一輸入孔之頂板； 士至少一表面形成有複數個培養單元、一接受部及複數 5個流道之培養板，對應於該頂板之-側，其中該複數個流 道2每一個培養單元連接，該接收部與該頂板之該輸入孔 重且用以接收由該輸入孔輸入之該流體，且每一培養單 兀具有一輸出孔，用以將該培養單元内過多之該流體排 出；以及 10 一底板，位於該培養板之一側，使得該培養板夹置於 该頂板與該底板之間’用以收集來自該頂板與該培養板之 流體； 其中，該流體由該頂板之輸入孔進入該培養板表面之 接收部，再經由該流道分流至每一個培養單元，最後再由 15該培養單元之輸出孔流出至該底板。 2.如申請專利範圍第1項所述之細胞培養裝置，其中 該底板表面形成有複數個與該培養板中每一培養.單元之該 輸出孔重疊之微管道，用以匯流或收集來自該培養板之= 養單元之該流體。 ° 20 3 ·如申請專利範圍第2項所述之細胞培養裝置，其中 該底板表面形成有一與該微管道連接之收集槽，用以收集 該流體。 ' 15 1323743 4·如申請專利範圍第3項所述之細胞培 包含一連接該底板之收集槽與該頂板輸人孔之卜乂其更 將於該收集槽之該流體迴流至該輸人孔。 ^管，以 5·如申請專利範圍第4項所述之細胞培養 該頂板與該培養板上相對㈣㈣叙位置分财成^中 溢出孔與-貫穿孔，以使該底板之收集槽經由該‘：：： 入 :該頂板之溢出孔、和該輸送管而與該頂板之輸 6·如申請專利範圍第丨項所述之細胞培養裝置，其中 10該頂板更包含複數個與該培養板之培養單元位置重叠ς開 口’用以檢測不同細胞間之交互作用。 7.如申請專利範圍第6項所述之細胞培養裝置，其中 該頂板與該培養板之培養單元間具有一生物性薄膜用以 提供細胞間相互作用之介面。 15 8.如申a青專利範圍第1項所述之細胞培養裳置，其中 該培養板之每一培養單元具有至少一微流管道，用以於細 胞間形成類似微血管之微管路。 9.如申請專利範圍第1項所述之細胞培養裝置，其中 該培養單元上批覆有一細胞間質，以利細胞附著。 20 1 〇.如申請專利範圍第1項所述之細胞培養裝置，其中 該頂板、該培養板與該底板之材質為透明材質。 11.如申請專利範圍第1項所述之細胞培養裝置，其中 該頂板、該培養板與該底板之材質為壓克力、聚碳酸酯 (PC)、或聚二曱基矽氧烷（PDMS)。 1323743 12. —種體外培養細胞的方法，包括以下步驟： (A)提供一細胞培養裝置，包含以下元件： 一具有一輸入孔之頂板； 至少一表面形成有複數個培養單元、一接受部及複數 個流道之培養板’對應於該頂板之―側，其_該複數個流 ，與每-個培養單元連接，該接收部與該頂板之輸入孔重 豐，用以接收由該輸入孔輸入之流體，且每一培養單元且 有一輸出孔，用以將該培養單元内過多之該流體排出；2 及 一底板，位於該培養板之一側，使得該培養板夹置於 該頂板與該底板之間，用以㈣來自該頂板與該培養板之 流體； 其中’該流體由該頂板之輸入孔進入該培養板表面之 15 接收部’再經由該流道分流至每—個培養單元，最後再由 該培養單元之輸出孔流出至該底板； (8)於遠培養單元表面上批覆—細胞間質；以及 (C)由該頂板之輸人孔注人-流體，該流體從該接收 道流至該培養單元，再由該培養板之輸出孔流 13·如申請專聽圍第12項所述之方法 面形成有—與該微管道連接之收集槽，用以表 一 14.如巾請專職圍第12項所述之方法，其更包^ 一連接该底板之收集槽與該頂板輸入孔之 '八 於該收集槽之流體迴流至該輸入孔。 ' B用以將 17 1323743 15.如申請專利範圍第12項所 之方法，其更包含於該 頂板形成複數㈣該培養板之培養單元位置㈣之開口， 以檢測不同細胞間之交互作用。 16·如申請專利範圍第15項所述之方法，其更包含提供 一位於該頂板之開π與該培養板之培養單元間之生物性薄 膜’以提供細胞間相互作用之介面。 17.如申請專利範圍第12項所述之方法，其更包含於該 ::養板之每一培養單元形成至少-微流管道，以於細胞間 才、擬微血管之微管路。 ίο 哕立8.如申叫專利範圍第丨2項所述之方法，其中該頂板、 Λ ^養板與該底板之材質為透明材質。 養裝19.如申請專利範圍第18項所述之方法，其中該細胞培 、置更包含一光偵測系統，以偵測細胞之活性。 18 1323743
50 圖5 1323743
TW092137188A 2003-12-26 2003-12-26 Apparatus for cell culture and method for culturing cells TWI323743B (en)

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US11/019,380 US7029907B2 (en) 2003-12-26 2004-12-23 Cell culture incubating apparatus and method using the same

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US20060263873A1 (en) * 2005-05-21 2006-11-23 Levine Leanna M Controlled flow microfluidic device and method of fabrication
US7820430B2 (en) * 2005-11-28 2010-10-26 Industrial Technology Research Institute Micro device for cell culture
US10119112B2 (en) * 2010-03-02 2018-11-06 Universite Technologie de Compiegne—UTC Multi-reactor unit for dynamic cell culture
TWI593798B (zh) * 2014-07-21 2017-08-01 財團法人工業技術研究院 三維細胞培養裝置與其應用

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EP1064353B1 (en) 1998-03-18 2002-11-06 Massachusetts Institute Of Technology Vascularized perfused microtissue/micro-organ arrays
US6734000B2 (en) 2000-10-12 2004-05-11 Regents Of The University Of California Nanoporous silicon support containing macropores for use as a bioreactor
AU2002257289A1 (en) * 2001-05-17 2002-11-25 The Board Of Trustees Of The Leland Stanford Junior University Device and method for three-dimensional spatial localization and functional interconnection of different types of cells

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