TWI388825B - Substrate - Google Patents

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TWI388825B
TWI388825B TW97135411A TW97135411A TWI388825B TW I388825 B TWI388825 B TW I388825B TW 97135411 A TW97135411 A TW 97135411A TW 97135411 A TW97135411 A TW 97135411A TW I388825 B TWI388825 B TW I388825B
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Taiwan
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fluid
nitrocellulose
zone
substrate
test piece
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TW97135411A
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Chinese (zh)
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TW201013181A (en
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Wen Pin Hsieh
Yi Jen Wu
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Actherm Inc
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Description

流體檢測試片之基板Substrate for fluid detection test piece

本發明係關於一種基板,特別是一種有關於生化檢測與免疫檢測所使用之流體檢測試片所使用的基板。The present invention relates to a substrate, and more particularly to a substrate for use in a fluid test strip for use in biochemical detection and immunoassays.

以流體檢測試片進行生化檢測與免疫檢測的習知技術中,流體檢測試片在其基板或底材上設計有流道或微流道結構,而因流道周圍並非吸水材質,且待測流體多為含有如蛋白質或是醣類等黏滯度高之組成物,所以當待測流體流過後,會在流道上殘留,使得待測流體無法完全反應,如此一來,不僅造成待測流體的浪費,更可能造成最終測試結果的誤差。In the conventional technique of performing biochemical detection and immunodetection using a fluid detecting test piece, the fluid detecting test piece is designed with a flow path or a micro flow path structure on the substrate or the substrate, and the surrounding of the flow path is not a water absorbing material, and is to be tested. The fluid is mostly composed of a highly viscous composition such as protein or saccharide. Therefore, when the fluid to be tested flows, it will remain on the flow path, so that the fluid to be tested cannot be completely reacted, thus not only causing the fluid to be tested. The waste is more likely to cause errors in the final test results.

此外,習知技術的流體檢測試片在流體傳送方面,可設計有微流道結構,並係利用微流道結構產生的毛細現象,將流體經過流道被動傳送至反應偵測區域;另一種方式則是在注入待測流體時即利用加壓等方式,給予流體一驅動力,使得流體可主動通過流道,到達反應偵測區域。但是無論是上述任一種方式,待測流體注入流道後常常產生大小不一的氣泡使得流道阻塞,造成實際測量上之誤差,甚至致使測試失敗。In addition, the fluid detecting test piece of the prior art can be designed with a micro-flow channel structure in fluid transfer, and utilizes the capillary phenomenon generated by the micro-flow path structure to passively transfer the fluid through the flow path to the reaction detecting area; The method is to apply a driving force to the fluid when the fluid to be tested is injected, that is, using a pressure or the like, so that the fluid can actively pass through the flow path to reach the reaction detecting area. However, in either of the above manners, after the fluid to be tested is injected into the flow channel, bubbles of different sizes are often generated to block the flow path, causing an error in actual measurement, and even causing the test to fail.

最後,習知技術的檢測試片,在製作上多使用模鑄或射出成型或壓印(imprint)的方式在基板上做出流道或微流道結構,所以必須使用聚乙烯(PE)、聚氯乙烯(PVC)或聚丙烯(PP)等價格較高之塑膠聚合物作為材質且模具耗損較快,進而造成試片之總體成本的提高。Finally, the test strips of the prior art use a die casting or injection molding or imprinting method to make a flow path or a micro flow path structure on the substrate, so polyethylene (PE) must be used. High-priced plastic polymers such as polyvinyl chloride (PVC) or polypropylene (PP) are used as materials and the molds are worn faster, which in turn leads to an increase in the overall cost of the test piece.

為克服上述之缺點,本發明提供一種流體檢測試片之基板,基板上表面向下凹設至少一流道,此流道包含依序連接之第一流體區、第二流體區與第三流體區,第一流體區係供流體之注入。此基板之特徵在於第二流體區與第三流體區之底部形成有硝化纖維層,此硝化纖維層包含有中空網狀構型,而流道中第二 流體區是供流體傳送之用,第三流體區是供流體反應之用,且第二流體區的硝化纖維層平均厚度不大於第三流體區硝化纖維層厚度。In order to overcome the above disadvantages, the present invention provides a substrate for a fluid detecting test piece, wherein an upper surface of the substrate is recessed downwardly with at least a first-class channel, the flow path including a first fluid region, a second fluid region and a third fluid region sequentially connected The first fluid zone is for fluid injection. The substrate is characterized in that a nitrocellulose layer is formed at the bottom of the second fluid region and the third fluid region, and the nitrocellulose layer comprises a hollow network configuration, and the second in the flow channel The fluid zone is for fluid transfer, the third fluid zone is for fluid reaction, and the average thickness of the nitrocellulose layer of the second fluid zone is no greater than the thickness of the nitrocellulose layer of the third fluid zone.

因此,本發明之主要目的,係提供一種流體檢測試片之基板,因具有可吸水的硝化纖維層,故可避免流道之待測流體殘留。Therefore, the main object of the present invention is to provide a substrate for a fluid detecting test piece which has a water-absorbing nitrocellulose layer, thereby avoiding residual fluid to be tested in the flow path.

本發明之另一目的,係提供一種流體檢測試片之基板,其具有可吸水的硝化纖維層,由於單位體積的硝化纖維吸水量係為定值,故可經由設定基板上硝化纖維層的體積,而提供流體的定量檢測。Another object of the present invention is to provide a substrate for a fluid detecting test piece having a water absorbing nitrocellulose layer. Since the water volume per unit volume of nitrocellulose is constant, the volume of the nitrocellulose layer on the substrate can be set. , while providing quantitative detection of fluids.

本發明之又一目的,係提供一種流體檢測試片之基板,具有中空網狀構型的硝化纖維層,由於流體流經中空網狀構型時,流體中的氣泡會被破壞,故可消彌較大的氣泡,避免微流道技術中氣泡阻塞流道的狀況發生,進而影響定量分析結果。Another object of the present invention is to provide a substrate for a fluid detecting test piece having a hollow network structure of a nitrocellulose layer, and the bubbles in the fluid are destroyed due to the fluid flowing through the hollow network configuration, so Larger bubbles prevent the occurrence of bubbles blocking the flow path in the microfluidic technology, which in turn affects the quantitative analysis results.

由於本發明係揭露一種流體檢測試片之基板,其中所利用物理、化學原理及溶液塗布技術,已為相關技術領域具有通常知識者所能明瞭,故以下文中之說明,不再作完整描述。同時,以下文中所對照之圖式,係表達與本發明特徵有關之示意,並未亦不需要依據實際情形完整繪製,合先敘明。Since the present invention discloses a substrate for a fluid detecting test piece, the physical, chemical, and solution coating techniques utilized therein are well known to those of ordinary skill in the art, and therefore, the description below will not be fully described. At the same time, the drawings in the following texts are indicative of the features related to the features of the present invention, and are not required to be completely drawn according to the actual situation.

如第1A圖所示,為本發明第一較佳實施例之流體檢測試片的基板示意圖。流體檢測試片的基板1自上表面10向下凹設有流道11,流道11包含有依序連接的第一流體區111、第二流體區112與第三流體區113。第一流體區111係供流體之注入,流體在注入第一流體區111後,經由第二流體區112的傳送,到達第三流體區113,流體中的待測成份在第三流體區113進行反應。又,在較佳的實施狀態中,基板1為生物相容(biocompatible)材料。FIG. 1A is a schematic view showing a substrate of a fluid detecting test piece according to a first preferred embodiment of the present invention. The substrate 1 of the fluid detecting test piece is recessed downward from the upper surface 10 with a flow path 11 including a first fluid region 111, a second fluid region 112 and a third fluid region 113 which are sequentially connected. The first fluid zone 111 is for the injection of a fluid. After the fluid is injected into the first fluid zone 111, the fluid is transferred to the third fluid zone 113 via the second fluid zone 112, and the component to be tested in the fluid is performed in the third fluid zone 113. reaction. Also, in a preferred embodiment, the substrate 1 is a biocompatible material.

請參考第1B圖,為第1A圖中沿AA連線之剖面圖。基板1的特徵在於,在第二流體區112與第三流體區113之底部均形成有硝化纖維層1121與1131,而硝化纖維層1121與1131的構型為中空網狀,此種具有多孔性的中空網狀結構,可以吸收由第一流體區111流入的流體,使得流體中的待測成份與存在於 硝化纖維層1131中的試劑進行反應。由於硝化纖維層1121與1131係為可吸水材質,故可避免流體殘留於流道11中,且由於流體流經中空網狀構型的硝化纖維層1121與1131時,流體中的氣泡會被破壞,故可避免氣泡阻塞流道11。此外,第二流體區112的硝化纖維層1121平均厚度Da不大於第三流體區113硝化纖維層1131厚度Db,亦即Da會小於或等於Db。此外,為降低所需生物檢體之體積,第二流體區112與第三流體區113的寬度Wa與Wb(如第1A圖所示)較佳至少為0.3mm。Please refer to Figure 1B for a cross-sectional view along line AA in Figure 1A. The substrate 1 is characterized in that nitrocellulose layers 1121 and 1131 are formed at the bottom of the second fluid region 112 and the third fluid region 113, and the nitrocellulose layers 1121 and 1131 have a hollow mesh shape, which is porous. Hollow network structure, which can absorb the fluid flowing in from the first fluid zone 111, so that the component to be tested in the fluid exists The reagent in the nitrocellulose layer 1131 is reacted. Since the nitrocellulose layers 1121 and 1131 are water absorbing materials, fluid can be prevented from remaining in the flow path 11, and bubbles in the fluid are destroyed as the fluid flows through the nitrocellulose layers 1121 and 1131 of the hollow network configuration. Therefore, it is possible to prevent the bubble from blocking the flow path 11. In addition, the average thickness Da of the nitrocellulose layer 1121 of the second fluid region 112 is not greater than the thickness Db of the nitrocellulose layer 1131 of the third fluid region 113, that is, Da may be less than or equal to Db. Further, in order to reduce the volume of the desired biological specimen, the widths Wa and Wb of the second fluid region 112 and the third fluid region 113 (as shown in Fig. 1A) are preferably at least 0.3 mm.

在製作上,硝化纖維層1121與1131的形成方式,係將硝化纖維粉末(nitrocellulose powder)與含有酯類(ester)和酮類(ketone)的有機溶劑混合後形成一硝化纖維溶液;再將形成後的硝化纖維溶液,澆注(casting)於第二流體區112與第三流體區113的底部,經乾燥後,於第二流體區112底部則會形成硝化纖維層1121,而於第三流體區113的底部則形成硝化纖維層1131。為達較佳的澆注效果,流道11之表面粗糙度(Ra值)以介於3微米至50微米之間為佳。In the production, the nitrocellulose layers 1121 and 1131 are formed by mixing a nitrocellulose powder with an organic solvent containing esters and ketones to form a nitrocellulose solution; The subsequent nitrocellulose solution is cast in the bottom of the second fluid zone 112 and the third fluid zone 113. After drying, a nitrocellulose layer 1121 is formed at the bottom of the second fluid zone 112, and in the third fluid zone. The bottom of 113 forms a nitrocellulose layer 1131. For better casting, the surface roughness (Ra value) of the flow path 11 is preferably between 3 and 50 microns.

硝化纖維溶液乾燥後形成具有中空網狀構型的硝化纖維層,為了調整較佳的中空網狀構型,本發明的硝化纖維溶液中,硝化纖維粉末與含有酯類和酮類的有機溶劑混合的較佳體積比例為1:9。由於單位體積的硝化纖維吸水量係為定值,故可由欲吸收之待測流體的體積推算出對應的硝化纖維溶液的體積,之後再行澆注。如此可以固定檢測所需液體之體積量,並適用於微量檢測。After the nitrocellulose solution is dried, a nitrocellulose layer having a hollow network configuration is formed. In order to adjust a preferred hollow network configuration, the nitrocellulose powder of the nitrocellulose solution of the present invention is mixed with an organic solvent containing an ester and a ketone. The preferred volume ratio is 1:9. Since the water absorption per unit volume of the nitrocellulose is constant, the volume of the corresponding nitrocellulose solution can be derived from the volume of the fluid to be absorbed, and then cast. This makes it possible to fix the volume of the liquid required for detection and to be suitable for micro-testing.

上述之第一較佳實施例係為具有三個流體區域的檢測試片基板,而根據本發明之精神,尚可在流道中加設第四流體區,以供儲存流道中多餘之流體。以下將就本發明之第二實施例具有四個流體區的檢測試片基板進行描述。The first preferred embodiment described above is a test strip substrate having three fluid regions, and in accordance with the spirit of the present invention, a fourth fluid region may be added to the flow path for storing excess fluid in the flow channel. A test strip substrate having four fluid regions of the second embodiment of the present invention will be described below.

請參考第2A圖,為本發明第二實施例之流體檢測試片的基板示意圖。基板2自上表面20向下凹設有流道21,流道21包含有依序連接的第一流體區211、第二流體區212、第三流體213區與第四流體區214。第一流體區211係供流體之注入,流體在注入第一流體區211後,經由第二流體區212的傳送, 到達第三流體區213,流體中的待測成份在第三流體區213反應。Please refer to FIG. 2A, which is a schematic diagram of a substrate of a fluid detecting test piece according to a second embodiment of the present invention. The substrate 2 is recessed from the upper surface 20 with a flow path 21, and the flow path 21 includes a first fluid region 211, a second fluid region 212, a third fluid 213 region and a fourth fluid region 214 which are sequentially connected. The first fluid zone 211 is for the injection of fluid, and after the fluid is injected into the first fluid zone 211, the second fluid zone 212 is transferred. Upon reaching the third fluid zone 213, the component to be tested in the fluid reacts in the third fluid zone 213.

請參考第2B圖,為第2A圖沿AA連線之剖面圖。在第二流體區212與第三流體區213之底部均形成有硝化纖維層2121與2131,且第二流體區212的硝化纖維層2121平均厚度Dc等於第三流體區213硝化纖維層2131厚度Dd。第四流體區214之底部與第二及第三流體區212、213相同,亦形成有硝化纖維層2141,且亦為中空網狀構型,以供多餘流體之貯存。而第四流體區214底部之硝化纖維層2141,在製作上,與第二及第三流體區212、213底部之硝化纖維層2121與2131相同,均以硝化纖維溶液經澆注於第二流體區212、第三流體區213與第四流體區214之底部再經乾燥後所形成。Please refer to Figure 2B for a cross-sectional view along line AA of Figure 2A. The nitrocellulose layers 2121 and 2131 are formed at the bottom of the second fluid region 212 and the third fluid region 213, and the average thickness Dc of the nitrocellulose layer 2121 of the second fluid region 212 is equal to the thickness Dd of the third fluid region 213 nitrocellulose layer 2131. . The bottom of the fourth fluid zone 214 is identical to the second and third fluid zones 212, 213, and is also formed with a nitrocellulose layer 2141 and also in a hollow mesh configuration for storage of excess fluid. The nitrocellulose layer 2141 at the bottom of the fourth fluid zone 214 is identical in fabrication to the nitrocellulose layers 2121 and 2131 at the bottom of the second and third fluid zones 212, 213, and is cast in the second fluid zone with the nitrocellulose solution. 212. The third fluid zone 213 and the bottom of the fourth fluid zone 214 are formed by drying.

此外,本實施例中第一流體區、第二流體區、第三流體區之構造、尺寸與相互連接關係、基板之較佳材料、表面粗糙度、基板中硝化纖維層之構型、形成方式、使用之硝化纖維溶液之成份與較佳比例,均與第一實施例相同,故在此不再重複贅述。In addition, in the present embodiment, the structure, the size and the interconnection relationship of the first fluid region, the second fluid region, and the third fluid region, the preferred material of the substrate, the surface roughness, the configuration of the nitrocellulose layer in the substrate, and the formation manner thereof The components and preferred ratios of the nitrocellulose solution used are the same as those of the first embodiment, and thus the description thereof will not be repeated here.

以上所述僅為本發明較佳實施例而已,並非用以限定本發明申請專利權利;同時以上的描述對於熟之本技術領域之專門人士應可明瞭與實施,因此其他未脫離本發明所揭示之精神下所完成的等效改變或修飾,均應包含於下述之申請專利範圍。The above description is only for the preferred embodiment of the present invention, and is not intended to limit the present invention. The above description is to be understood by those skilled in the art, and thus the other embodiments are not disclosed. Equivalent changes or modifications made in the spirit of the invention are to be included in the scope of the claims below.

基板‧‧‧1、2Substrate ‧‧1,2

上表面‧‧‧10、20Upper surface ‧‧10,20

11、21‧‧‧流道11, 21‧‧‧ runners

111、211‧‧‧第一流體區111, 211‧‧‧ first fluid zone

112、212‧‧‧第二流體區112, 212‧‧‧Second fluid zone

113、213‧‧‧第三流體區113, 213‧‧‧ third fluid zone

214‧‧‧第四流體區214‧‧‧Fourth fluid zone

1121、13、2121、2131、2141‧‧‧硝化纖維層1121, 13, 2121, 2131, 2141‧‧ ‧ nitrocellulose layer

Da‧‧‧硝化纖維層平均厚度Da‧‧‧ average thickness of nitrocellulose layer

Db‧‧‧硝化纖維層厚度Db‧‧‧Nitrocellulose layer thickness

Dc‧‧‧硝化纖維層平均厚度Dc‧‧‧ average thickness of nitrocellulose layer

Dd‧‧‧硝化纖維層厚度Dd‧‧‧Nitrocellulose layer thickness

Wa‧‧‧第二流體區的寬度Wa‧‧‧Width of the second fluid zone

Wb‧‧‧第三流體區的寬度Wb‧‧‧ width of the third fluid zone

第1A圖,為本發明第一實施例流體檢測試片的基板之示意圖。Fig. 1A is a schematic view showing a substrate of a fluid detecting test piece according to a first embodiment of the present invention.

第1B圖,為本發明第一實施例流體檢測試片的基板剖面之示意圖。Fig. 1B is a schematic view showing a cross section of a substrate of a fluid detecting test piece according to a first embodiment of the present invention.

第2A圖,為本發明第二實施例流體檢測試片的基板之示意圖。Fig. 2A is a schematic view showing a substrate of a fluid detecting test piece according to a second embodiment of the present invention.

第2B圖,為本發明第二實施例流體檢測試片的基板剖面之示意圖。Fig. 2B is a schematic view showing a cross section of a substrate of a fluid detecting test piece according to a second embodiment of the present invention.

基板‧‧‧1Substrate ‧‧1

第一流體區‧‧‧111First fluid area ‧‧11111

第二流體區‧‧‧112Second fluid zone ‧‧‧112

第三流體區‧‧‧113Third fluid zone ‧‧‧113

硝化纖維層‧‧‧12、13Nitrocellulose layer ‧‧‧12,13

硝化纖維層平均厚度‧‧‧DaAverage thickness of nitrocellulose layer ‧‧Da

硝化纖維層厚度‧‧‧DbNitrocellulose layer thickness ‧‧‧Db

第二流體區的寬度‧‧‧WaWidth of the second fluid zone ‧‧Wa

第三流體區的寬度‧‧‧WbWidth of the third fluid zone ‧‧‧Wb

Claims (8)

一種流體檢測試片之基板,該基板自其上表面向下凹設至少一流道,該流道包含依序連接之第一流體區、第二流體區與第三流體區,該第一流體區係供流體之注入,其特徵在於:該第二流體區與第三流體區之底部形成有硝化纖維層,該硝化纖維層包含有中空網狀構型,其中該硝化纖維層係由硝化纖維溶液所形成,且該硝化纖維溶液係由硝化纖維粉末與酯類及酮類溶劑以較佳的比例1:9所混合而成,該第二流體區係供流體之傳送,該第三流體區係供流體之反應,且該第二流體區的硝化纖維層平均厚度不大於該第三流體區硝化纖維層厚度,以及該第二流體區與第三流體區的最小寬度為0.3 mm。 a substrate for a fluid detecting test piece, the substrate is recessed downwardly from the upper surface thereof, at least a first channel, the flow channel comprising a first fluid zone, a second fluid zone and a third fluid zone sequentially connected, the first fluid zone The injection of the fluid is characterized in that: a nitrocellulose layer is formed at the bottom of the second fluid zone and the third fluid zone, and the nitrocellulose layer comprises a hollow network structure, wherein the nitrocellulose layer is composed of a nitrocellulose solution. Formed, and the nitrocellulose solution is formed by mixing nitrocellulose powder with an ester and a ketone solvent in a preferred ratio of 1:9, the second fluid zone is for fluid transfer, and the third fluid zone is The fluid is reacted, and the average thickness of the nitrocellulose layer of the second fluid zone is not greater than the thickness of the nitrocellulose layer of the third fluid zone, and the minimum width of the second fluid zone and the third fluid zone is 0.3 mm. 如申請專利範圍第1項的流體檢測試片之基板,其中該第二流體區的硝化纖維層平均厚度小於該第三流體區硝化纖維層厚度。 The substrate of the fluid detecting test piece according to claim 1, wherein the average thickness of the nitrocellulose layer of the second fluid region is smaller than the thickness of the nitrocellulose layer of the third fluid region. 如申請專利範圍第2項的流體檢測試片之基板,其中該硝化纖維層係以硝化纖維溶液經澆注於第二流體區與第三流體區之底部再經乾燥後所形成。 The substrate for a fluid detecting test piece according to claim 2, wherein the nitrocellulose layer is formed by pouring a nitrocellulose solution into the bottom of the second fluid zone and the third fluid zone and drying. 如申請專利範圍第2項的流體檢測試片之基板,其中該流道之表面粗糙度為3微米至50微米之間。 The substrate of the fluid detecting test piece of claim 2, wherein the flow path has a surface roughness of between 3 micrometers and 50 micrometers. 如申請專利範圍第1項的流體檢測試片之基板,其中該第二流體區的硝化纖維層平均厚度等於該第三流體區硝化纖維層厚度。 The substrate of the fluid detecting test piece of claim 1, wherein the average thickness of the nitrocellulose layer of the second fluid zone is equal to the thickness of the nitrocellulose layer of the third fluid zone. 如申請專利範圍第5項的流體檢測試片之基板,其中該流道進一步包括第四流體區,該第四流體區之底部亦形成有硝化纖維層,該硝化纖維層包含有中空網狀構型,供多餘流體之貯存。 The substrate for a fluid detecting test piece according to claim 5, wherein the flow path further comprises a fourth fluid region, and a bottom of the fourth fluid region is also formed with a nitrocellulose layer, the nitrocellulose layer comprising a hollow network structure Type for storage of excess fluid. 如申請專利範圍第6項的流體檢測試片之基板,其中該硝化纖維層係以硝化纖維溶液經澆注於第二流體區、第三流體區與第四流體區之底部再經乾燥後所形成。 The substrate for a fluid detecting test piece according to claim 6, wherein the nitrocellulose layer is formed by pouring a nitrocellulose solution into the second fluid zone, the third fluid zone and the bottom of the fourth fluid zone, and then drying. . 如申請專利範圍第6項的流體檢測試片之基板,其中該流道之表面粗糙度為3微米至50微米之間。 A substrate for a fluid detecting test piece according to claim 6 wherein the surface roughness of the flow path is between 3 micrometers and 50 micrometers.
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