TWI252806B - Multichannel and multilayer pharmaceutical device - Google Patents
Multichannel and multilayer pharmaceutical device Download PDFInfo
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- TWI252806B TWI252806B TW093100052A TW93100052A TWI252806B TW I252806 B TWI252806 B TW I252806B TW 093100052 A TW093100052 A TW 093100052A TW 93100052 A TW93100052 A TW 93100052A TW I252806 B TWI252806 B TW I252806B
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B18/00—Layered products essentially comprising ceramics, e.g. refractory products
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
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- B29C65/00—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
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- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
- B81C1/00119—Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
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- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
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- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
- B01J2219/00317—Microwell devices, i.e. having large numbers of wells
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/12—Specific details about manufacturing devices
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B01L2300/0819—Microarrays; Biochips
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- B01L2300/0887—Laminated structure
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- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2203/00—Basic microelectromechanical structures
- B81B2203/03—Static structures
- B81B2203/0323—Grooves
- B81B2203/0338—Channels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
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- C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
- C04B2235/65—Aspects relating to heat treatments of ceramic bodies such as green ceramics or pre-sintered ceramics, e.g. burning, sintering or melting processes
- C04B2235/656—Aspects relating to heat treatments of ceramic bodies such as green ceramics or pre-sintered ceramics, e.g. burning, sintering or melting processes characterised by specific heating conditions during heat treatment
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- C04B2237/00—Aspects relating to ceramic laminates or to joining of ceramic articles with other articles by heating
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Description
1252806 五、發明說明(1) 一、 【發明所屬之技術領域】 本發明之技藝範圍乃同時測試生物/化學相互作用之 多個化合物。尤其,本發明是一種裝置/結構,及一種測 試藥物交互作用的方法。 二、 【先前技術】 在製藥工業中,測試化學材料A與化學材料B「B A間 的反應(包括生物活性)是必要的,上述的η可以是一個 大的數字,達到百萬的等級。 一種普遍的方法是在一塊塑膠卡上提供一材料陣列Β厂 Β η,然後放置材料Α使之與每一種Β接觸。商業上可以取得 的塑膠卡陣列包含9 6及3 8 4個井(we 1 1 )。井的直徑大約為 幾毫米的等級。化學材料的放置或分配方式通常是利用微 量吸管。可以使用電腦協控的掃描器以分類化學相互作 用。 由於進行測試排除可能性的化學材料有幾百種組合, 需要花費與製藥相關之公司幾年的時間進行藥物研發,才 能得到一成功藥物上市。利用本電腦協助掃描裝置的速 度,將可以縮短藥物研發的時間,例如,增加同一時間内 樣本掃描的速度。舉例來說,如果我們在特定的體積之下 可以裝入更多數量的井,便可能增加速度。於特定體積中 數量較多的井,也可以減少使用於每個井中昂貴化學材料
4IBM03139TW.ptd 第6頁 1252806 五、發明說明(2) 的量。 本塑膠卡通常是利用射出成型的方式形成,每一陣列 之中,每個孔洞直徑及位置的精準度並不足以製造出微孔 及通道。這必定限制了這個領域中的塑膠伸展性。 製藥工業正在積極尋找具有數千個井,且直徑達到 1 0 0微米等級的微型裝置,且在陣列之中,通道可連接不 同水平的選擇性井。 三、【發明内容】 本發明與一種陶瓷的裝置有關,且此裝置具有微井及 微通道,本發明也與形成上述裝置之方法有關。 本發明的一項特點為,陶瓷結構中的微井及微通道的 製造,是經過層壓(1 a m i n a t i n g )多塊個別的生胚片 (greensheet)0 一方面,本發明之開放式井及通道是由獨立層個別化 所形成。 另一方面,井及通道結構的多層陣列含有一組構造, 該構造由燒結後形成通道的材料所構成。
4IBM03139TW.ptd 第7頁 五 發明說明(3) 本發明 的另外— 井、通道;5、亡 貝特點為使用女丨 ^些孔隙。 材枓移除技術,以形成 本發明的另外— material), —項特點為使用犧在k結的過程 #材料(sacri f icial太私 ,可從陶究結構中逸散。 本發明的另外 不會有殘留 物 項特點為使用 犧牲材料’在燒結後將 本發明的另外_ |材料,在燒結接# Γ項特點為使用 後這些井將會連7 =用會留下多孔構造的犧牲 接起來 或金屬或組合物)以於項—特二為使用不可密化的材料(無機 本發明的另外 ^ Λ' 道。 ' 可密化基體(matrix)中形成通 本發明的另外—項特 |積的控制。 、在燒結的過程中對通道體 本發明的另外一項特點 因化學分解作用或氣相沉在通道中使用一種材料, 積後而留下一塗芦。 四 實施方式 圖1顯示出根據本發明 μ 心間化的完整結構,具有一個 4IBM03139TW.ptd 1252806 五、發明說明(4) 單一的水平通道2 5形成於1 0 - 2層,連接形成於1 0 - :1、1 0 - 2 及1 0 - 3層中之第一個垂直的孔隙2 2,以及於1 0 - 3層之孔隙 24。10-1至10 - 3層在一開始是分離的陶竟生胚片,經過一 般的過程進行層壓及燒結,而形成陶瓷板1 0。在操作時, 一種材料會被向上推進而通過1 0 - 1層,於1 0 - 3層的二個位 置分離出去。同樣地,流動的方向可能是相反的,有二種 材料進入1 0 - 3層的二個孔隙,於1 0 - 1層的單一開口結合出 去。 圖1顯示利用三塊生胚片及一個水平通道連接二個垂 直井所形成的結構,以便於說明。此結構已經由層壓而將 個別的薄片組合起來。組合的過程與陶竟結構是一致的, 陶瓷結構係具有幾千個孔的陣列,且具有幾千個水平的通 道,選擇性地連接至相連的垂直孔。陶瓷材料可包括氧化 鋁、玻璃陶瓷、氮化鋁、硼化矽玻璃及玻璃。 垂直井的直徑可以為2 01¾米或以上,通道的寬度可以 為2 0微米或以上,且長度最小值為2 0微米。這種接觸一材 料的井形狀可以為圓形、長方形、平滑或粗糙。板1 0的總 厚度可以為任何期望的值,但較佳係小於1毫米。生胚片 的厚度乃依據應用的不同而異,但是較佳的範圍介於約3 哩至約30哩之間。 層壓的過程包括加熱、壓力及時間。較佳的層壓壓力
4IBM03139TW.ptd 第9頁 1252806 燒結 五、發明説明(5) 為8 0 0 p s i以下’溫度為9 0°C以下,時間少於5分鐘 的過程包括選擇材料及用以形成生胚片的接合系統 圖2 A至2 C顯示出分離的生胚片1 〇 一卜1 〇 一 2及1 〇 - 3,這 些生胚片已經經過層壓而形成圖1的結構。其說明如下, 水平通道2 5的長度大於孔隙2 2或2 4之直徑的二倍。其說明 如下,孔隙2 2的直徑大約為2 〇微米以上。用來製造的直徑 將依據特殊應用及技術之差異性而有所不同,例如通過材 料的黏性、表面及流體的表面張力/活性、期望的流力、 毛細作用或增壓直流、期望的量及流速等。 根據本發b月’生胚片是從如氧化鋁 及陶瓷等材料所形成的。製作垂直 ,陶瓷玻璃 是將藉由技術將材料移除,技術舉例來;:平通道的技術 包括切削、雷射鑽孔、電子束 °兄為將材料打穿’ I射。 、砂磨及高,液體噴 精由將材料壓至邊側並使生胚 (miCromolding)並不包含較佳者片艾形的微成型 材料置換技術。這些技術是不ί望二 ^巾,通常會被歸類為 及通道位置間之準確度相當小,、坐因為所希望的各井 |置換技術所引導的變形對於提供° =米,i經由材料 一 度是一大障礙。 弟一個實施例的易揮發材料可以日 疋任何的可相容有機 4IBM03139TW.Ptd 第10頁 1252806 •五、發明說明(6) 甲酸、石告斗、# a或其他有機材料 例
材料,例如J 在第二個實施例之中,少 瓷,如氧化鋁、破螭陶j,成多孔結構的材料可 的大小少於40微米。 、虱化鋁及硼化矽破螭,其微粒 水平以及垂直孔隙可处 力不在意日寺,或者是其他二下:口,此係當處理時的壓 揮發材料。 *作扭曲之,或者是被填入一易 在本發明的第一個實施例 :會;存的材料。移除易揮發封料的ί 23=離開後 而至環境中;或二^丨ί 度,使材料以蒸氣的型態離開 將易揮發材^ =组技術,包括燃燒或其他化學反應, 插:: 子與反應劑氣體的分子結合,以形成- 能較;為氣體並且逸散至環境。易揮發材料的型 :型能谷易塗抹在生胚片之孔隙中的塑‘態’例如-糊狀 人 f第一個實施例之中,易揮發材料與第二個材料妗 ^ 並且將形成一種燒結而成的多孔構造,例如一種易 毛=tl之微粒型態的混合物,顆粒大小足以使顆粒可以】 未、TO i的狀怨下接觸。因此,一個持續開孔的材 後仍然會伴技 ^ ^ m r + . 、、 π „ 牧k結 1示符—開孔的基質(m a t r l χ ),而可以讓測★式
4IBM03139TW.Ptd
1252806 ----^ 五、發明說明(?) 從板1 0的一側流、局 、_ 燒結的多孔體將可 ^至其他板。更為顯著的是通道_未 而且,通道中未=形成被控制的開放體積及通道直徑。 過程中塌陷。&結的多孔體將有助於避免通道在燒結的 圖6為對應於 一 直的孔隙是開放的,的#分,顯示出完整的構造,其t垂 且水平通道含有一 “ f燒結之前已經被填入易揮發材料, 前已經被填入充埴^二孔的基質。水平通道2 2 5在燒結之 質材料的混合物,、細:,這個充填材料是易揮發材料及基 放的孔洞而可以讓;結;形成一種多孔基質,具有開 裱*體欠垂直孔隙22流至垂直孔隙24。 圖7 Α及7 C顯示φ a 樣填入相同易揮於好肱片Μ — 1及2〇一2,係如之前的例子 生胚片。 χ材料222。圖8Β顯示具有孔隙空洞的 圖8顯不2〇-1極2〇〜2之次薄板(subHmin 1 入充填材料2 25的水平孔隙。其說明如下: 2 225疋易、揮發材#與上列之顆粒的混合物,經過燒結
4將I A種開孔的結構。依設計的觀點,垂直通道— :填:多孔材料,Μ達到設計之目㈤。圖1〇顯示出燒結 前的最終結構。 本發明的另一種形式包括使用一種可密化的材料製作
1252806 五、發明說明(8) 生胚片,並且以不可密化的材料填入開孔,以維持通道的 直徑。例如,基質材料可能是一種無機相,如氧化銘與玻 璃粉混合以進行密化,然而,於通道(及或孔洞)中卻是不 可密化的材料,可以是剛好大於陶瓷顆粒如氧化鋁。 此外,通道的材料可以在燒結處形成非多孔性覆蓋 層,如此可使通道具有内襯,如此的覆蓋層具有二種表面 能量/活性,而比板1 0的基質材料/本體更多。覆蓋層的材 料可以為無機物、金屬或合成物。覆蓋層的形成是由於薄 板中的第一個材料與充填物中的第二個材料之間的化學分 解作用所致,或者是於四周氣體及/或覆蓋層的形成是由 於氣相沉積所致。另外一種選擇為,由充填材料所散發出 的蒸氣,沉積於壁上而形成内襯,或與薄板中所含有的材 料產生反應而形成。 雖然本發明已經以一些較佳的實施例加以描述,可以 讓習知技藝者了解本發明在下列之申請專利範圍的精神和 領域之中,以不同的版本實行。
ϋ
4IBM03139TW.ptd 第13頁 1252806 圖式簡單說明 五、【圖式簡單說明】 圖1 顯示經過一第一種過程後之一完整結構。 圖2 - 5顯示第一個過程中的步驟。 圖6 顯示經過一第二種過程後之一完整結構。 圖7 - 1 0 顯示第二個過程中的步驟。 圖式元件符號說明 22 孔隙 24 孔隙 2 5 水平通道 2 2 2易揮發材料 2 2 5水平通道
4IBM03139TW.ptd 第14頁
Claims (1)
1252806 六、申請專利範圍 1. 一種形成一種板的方法,使至少一種物質可以通過一組 孔隙,從一第一側到達一第二側,該方法包含以下的步 驟: 形成複數個垂直孔隙在一第一個陶瓷生胚片(c e r a m i c greensheet); 形成複數個水平孔隙在一第二個陶瓷生胚片; 形成複數個垂直孔隙在一第三個陶瓷生胚片,其中, 至少某些該第二個生胚片中的該水平孔隙連接該第一個生 胚片的一個孔隙與該第三個生胚片的一個孔隙; 填入一種包含一易揮發材料(fugitive material)之 充填材料於至少某些該孔隙; 將該第一個、第二個及第三個陶瓷生胚片層壓在一 起;以及 燒結該第一個、第二個及第三個生胚片,從而形成該 板5並且釋放出該易揮發材料。 2 .如申請專利範圍第1項所述之方法,其中: 形成至少該第一個、第二個及第三個生胚片之一的該步 驟,將受到一種材料移除技術的影響。 3 .如申請專利範圍第1項所述之方法,其中: 該第二個生胚片與該第一個及第三個生胚片之一層壓在一 起,以在之後該易揮發材料填入該孔隙的步驟前形成一個 次薄板。
4IBM03139TW.ptd 第15頁 1252806 六、申請專利範圍 4 .如申請專利範圍第1項所述之方法,其中: 該第一個、第二個及第三個生胚片的孔隙,在與其他該生 胚片層壓之前,將該易揮發材料填入。 5 .如申請專利範圍第1項所述之方法,其中: 於該第一個、第二個及第三個生胚片之一中的孔隙並未以 該易揮發材料填入。 6 .如申請專利範圍第2項所述之方法,其中: 該易揮發材料在一燒結的過程中逸散且不會留下一殘留 物。 7 .如申請專利範圍第3項所述之方法,其中: 該易揮發材料在一燒結的過程中逸散且不會留下一殘留 物。 8 .如申請專利範圍第4項所述之方法,其中: 該易揮發材料在一燒結的過程中逸散且不會留下一殘留 物。 9 .如申請專利範圍第2項所述之方法,其中: 填入該孔隙的該充填材料是一種易揮發材料的一種混合 物,在一燒結的過程中逸散且不會留下一殘留物,以及一
4IBM03139TW.ptd 第16頁 1252806 六、申請專利範圍 種基質材料,在該燒結過程後留下一個多孔的基質。 1 0 .如申請專利範圍第3項所述之方法,其中: 填入該孔隙的該充填材料是一種易揮發材料的一種混合 物,在一燒結的過程中逸散且不會留下一殘留物,以及一 種基質材料,在該燒結過程後留下一個多孔的基質。 1 1 .如申請專利範圍第4項所述之方法,其中: 填入該孔隙的該充填材料是一種易揮發材料的一種混合 物,在一燒結的過程中逸散且不會留下一殘留物,以及一 種基質材料,在該燒結過程後留下一個多孔的基質。 1 2 .如申請專利範圍第1項所述之方法,其中: 該易揮發材料是選自於以下的材料,包含對苯二甲酸以及 碳。 1 3 .如申請專利範圍第9項所述之方法,其中: 該易揮發材料是選自於以下的材料,包含:對苯二甲 酸以及碳;以及 該基質材料是選自於以下的材料,包含: 陶瓷如氧化鋁、玻璃陶瓷、氮化鋁以及硼化矽玻璃。 1 4. 一種形成一種板的方法,使至少一種物質可以通過一 組孔隙,從第一側到達第二側,該方法並包含以下的步
4IBM03139TW.ptd 第17頁 1252806 六、申請專利範圍 驟: 形成複數個垂直孔隙在一第一個陶瓷生胚片; 形成複數個水平孔隙在一第二個陶瓷生胚片; 形成複數個垂直孔隙在一第三個陶瓷生胚片,其中, 至少某些該第二個生胚片中的該水平孔隙連接該第一個生 胚片的一個孔隙與該第三個生胚片的一個孔隙; 將該第一個、第二個及第三個陶瓷生胚片層壓在一 起;以及 燒結該第一個、第二個及第三個生胚片。 1 5 .如申請專利範圍第1 4項所述之方法,其中: 形成至少一該第一個、第二個及第三個生胚片的該步驟, 將會受到一種材料移除技術的影響。 1 6 .如申請專利範圍第1 4項所述之方法,其中·· 該第二個生胚片與該第一個或第三個生胚片其中之一層壓 在一起,以形成一個次薄板。 1 7 .如申請專利範圍第1 5項所述之方法,其中: 該第二個生胚片與該第一個或第三個生胚片其中之一層壓 在一起,以形成一個次薄板。
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US5976472A (en) * | 1997-10-15 | 1999-11-02 | Eastman Kodak Company | Integrated micro-ceramic chemical plant with insertable catalytic reaction chambers |
US6572830B1 (en) | 1998-10-09 | 2003-06-03 | Motorola, Inc. | Integrated multilayered microfludic devices and methods for making the same |
JP2003517591A (ja) | 1999-12-09 | 2003-05-27 | モトローラ・インコーポレイテッド | 分析試料の反応を行うための多層微量流体デバイス |
JP2001247376A (ja) * | 2000-03-02 | 2001-09-11 | Hitachi Koki Co Ltd | インクジェットヘッド等のセラミック製中空部品の製造方法 |
JP2002121078A (ja) * | 2000-10-10 | 2002-04-23 | Sumitomo Metal Electronics Devices Inc | 焼結体の製造方法 |
-
2003
- 2003-01-07 US US10/338,093 patent/US6955777B2/en not_active Expired - Lifetime
- 2003-11-25 EP EP03790042A patent/EP1587764A4/en not_active Withdrawn
- 2003-11-25 JP JP2004566498A patent/JP4553193B2/ja not_active Expired - Fee Related
- 2003-11-25 CN CNB2003801082117A patent/CN100427418C/zh not_active Expired - Lifetime
- 2003-11-25 AU AU2003293051A patent/AU2003293051A1/en not_active Abandoned
- 2003-11-25 WO PCT/US2003/037693 patent/WO2004063103A1/en active IP Right Grant
- 2003-11-25 KR KR1020057010254A patent/KR100724633B1/ko not_active IP Right Cessation
-
2004
- 2004-01-02 TW TW093100052A patent/TWI252806B/zh not_active IP Right Cessation
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2005
- 2005-07-04 IL IL169511A patent/IL169511A/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
KR20050098229A (ko) | 2005-10-11 |
WO2004063103A1 (en) | 2004-07-29 |
AU2003293051A1 (en) | 2004-08-10 |
TW200508016A (en) | 2005-03-01 |
EP1587764A4 (en) | 2009-04-15 |
US20040129371A1 (en) | 2004-07-08 |
CN100427418C (zh) | 2008-10-22 |
CN1735567A (zh) | 2006-02-15 |
EP1587764A1 (en) | 2005-10-26 |
US6955777B2 (en) | 2005-10-18 |
JP2006513064A (ja) | 2006-04-20 |
JP4553193B2 (ja) | 2010-09-29 |
KR100724633B1 (ko) | 2007-06-04 |
IL169511A (en) | 2008-12-29 |
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