TWI569010B - Three dimensional flowing channel paper substrate sensor that applicable for biological testing chip and its making method - Google Patents

Three dimensional flowing channel paper substrate sensor that applicable for biological testing chip and its making method Download PDF

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TWI569010B
TWI569010B TW104133617A TW104133617A TWI569010B TW I569010 B TWI569010 B TW I569010B TW 104133617 A TW104133617 A TW 104133617A TW 104133617 A TW104133617 A TW 104133617A TW I569010 B TWI569010 B TW I569010B
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paper substrate
paper
flow path
sensor
layer
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TW201713943A (en
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莊承鑫
張凱傑
張龍右
吳熏培
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南臺科技大學
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應用於生物檢測晶片之具三維流道紙基板感測器及其製造方法Three-dimensional flow path paper substrate sensor applied to bio-detection wafer and manufacturing method thereof

本發明係關於一種紙基板感測器及其製造方法,尤指應用於生物檢測晶片且具三維流道之感測器者。The present invention relates to a paper substrate sensor and a method of fabricating the same, and more particularly to a sensor for a biometric wafer and having a three-dimensional flow path.

根據Total Biosensor Market 2016年市場分析調查當中顯示,生物檢測器用於居家照護將會是生醫檢測未來之發展方式,且預估將有超過65%以上的使用族群著重於家庭診斷,使病患能於家中透過簡便且低成本的設備達到檢測功能。由於紙張具有低成本、高生產性及通用性…等特點,且利用紙張所製成之感測器能適用於較彈性、可移植、一次性及能簡易操作之檢測,其所賦予之可攜性、便利性及立即性使紙型感測器逐漸成為生物感測器未來之發展趨勢。According to the Total Biosensor Market 2016 market analysis survey, bio-detectors for home care will be the way for biomedical testing to develop in the future, and it is estimated that more than 65% of the user population will focus on family diagnosis, enabling patients to The detection function is achieved at home through simple and low-cost equipment. Due to the low cost, high productivity and versatility of paper, and the sensor made of paper can be used for flexible, portable, disposable and easy-to-operate detection, it is portable. Sex, convenience and immediacy make paper sensors gradually become the future trend of biosensors.

相關之先前技術,請參閱中華民國公開第201116412號專利,係揭露一種「網版印刷之功能性微系統」,其係於一基材上透過網版印刷使該基材上沈積有複數層第一墨水沈積物結構及第二墨水沈積物結構,並使第二墨水沈積物結構位於第一墨水沈積物結構相對處,位於第一及第二墨水沈積物結構之間上方設有外罩,以藉第一及第二墨水沈積物結構、基材及外罩界定一微流道,藉此,透過網版印刷多層堆疊之方式製作具不同電極厚度之感測器,進而控制感測器微流道高度,並利用電化學方或偵測檢測細胞與細菌之阻抗變化,藉以觀測出阻抗與濃度間之關係。For related prior art, please refer to the Patent No. 201116412 of the Republic of China, which discloses a "functional microsystem for screen printing" which is formed by depositing a plurality of layers on a substrate by screen printing. An ink deposit structure and a second ink deposit structure, and the second ink deposit structure is located opposite the first ink deposit structure, and a cover is disposed between the first and second ink deposit structures to The first and second ink deposit structures, the substrate and the outer cover define a micro flow channel, thereby forming a sensor with different electrode thicknesses by means of a screen printing multilayer stack, thereby controlling the sensor micro flow path height And use electrochemical or detection to detect changes in impedance between cells and bacteria to observe the relationship between impedance and concentration.

而,中國大陸公告第103041876號專利,係揭露一種「三維微流控紙芯片的製備及在現場電化學檢測中的應用」,其係於三張濾紙上批量打印出疏水蠟圖案,待熔蠟成型後,於濾紙上批量網印陣列工作電極、參比電極與對電極,並於濾紙的無工作電極面上批量打印辣根過氧化物酶和氧化酶,接著,裁剪紙芯片後透過雙面膠片粘合濾紙以構成電化學三維微流控紙芯片夾。In addition, the Chinese Patent Publication No. 103041876 discloses a "three-dimensional microfluidic paper chip preparation and application in on-site electrochemical detection", which is a series of hydrophobic wax patterns printed on three filter papers to be melted wax. After molding, the array working electrode, the reference electrode and the counter electrode are screen printed on the filter paper, and the horseradish peroxidase and oxidase are batch-printed on the non-working electrode surface of the filter paper, and then the paper chip is cut and then passed through both sides. The film is bonded to the filter paper to form an electrochemical three-dimensional microfluidic paper chip holder.

另,美國公告第8628729號專利,係揭露一種「三維微流體裝置」,其係包含至少二圖案化之多孔親水層,且於每一親水層設有不透液阻擋層並滲透親水層之厚度以形成限定邊界,位於二親水層以及每二個相鄰之親水層之間設有不透液層,且不透液層具有一對準至少一相鄰親水層內之至少一部分親水性區域的開口,並將一或多種試劑設置於親水區域以及親水區域之檢測區,用以比色檢測該檢測區中所存在之分析物。In addition, U.S. Patent No. 8,826,729 discloses a "three-dimensional microfluidic device" comprising at least two patterned porous hydrophilic layers, and each of the hydrophilic layers is provided with a liquid-impermeable barrier layer and penetrates the thickness of the hydrophilic layer. Forming a defined boundary, a liquid-impermeable layer is disposed between the two hydrophilic layers and each of the two adjacent hydrophilic layers, and the liquid-impermeable layer has at least a portion of the hydrophilic region aligned with at least one adjacent hydrophilic layer. Opening, and one or more reagents are disposed in the hydrophilic region and the detection region of the hydrophilic region for colorimetric detection of the analyte present in the detection zone.

有鑑於生物檢測器具有能減少檢體及試劑量、縮短反應時間、減少設備成本…等優點,而逐漸被廣為運用。是以,本發明之目的乃是透過將具不同功能之紙張多層堆疊於紙基材以建立一三維微流體帶,並藉此達成檢體過濾與檢測之功效。In view of the advantages of biodetectors, such as reducing the amount of samples and reagents, shortening reaction time, and reducing equipment costs, they are widely used. Therefore, the object of the present invention is to establish a three-dimensional microfluidic tape by stacking paper sheets having different functions on a paper substrate, thereby achieving the effects of sample filtration and detection.

本發明之另一目的係配合生物免疫反應機制使所製成之感測器能應用於多種檢測領域,並達到快速、高靈敏度之免疫分析檢測。Another object of the present invention is to enable the prepared sensor to be applied to various detection fields in combination with a biological immune reaction mechanism, and to achieve rapid and high sensitivity immunoassay detection.

為達前揭目的,本發明之其中一種技術手段在於提供一種應用於生物檢測晶片之具三維流道紙基板感測器製造方法,該方法包含︰ (a)  將導電溶液印刷於一紙基板以形成具特定形狀之電極圖案; (b) 分別於該紙基板及一濾紙噴塗膠粘劑,並使膠體固化,而於該紙基板及該濾紙形成疏水區域,使該濾紙具有一流道而構成運輸層; (c)  於該電極圖案表面修飾可結合待檢測分子之抗體奈米粒子以構成一傳感層; (d) 以親水膠依序將該傳感層及該運輸層貼合於一吸收層;以及 (e)  構成一紙基板感測器。In order to achieve the foregoing, one of the technical means of the present invention is to provide a method for manufacturing a three-dimensional flow path paper substrate sensor applied to a bio-detection wafer, the method comprising: (a) printing a conductive solution on a paper substrate Forming an electrode pattern having a specific shape; (b) spraying the adhesive on the paper substrate and a filter paper respectively, and solidifying the colloid, and forming a hydrophobic region on the paper substrate and the filter paper, so that the filter paper has a first-class track to constitute a transport layer; (c) modifying the surface of the electrode pattern to bind the antibody nanoparticles of the molecule to be detected to form a sensing layer; (d) sequentially bonding the sensing layer and the transport layer to an absorbing layer with a hydrophilic gel; And (e) constituting a paper substrate sensor.

於本發明之一較佳實施例中,該步驟(a)之印刷方式為網版印刷。In a preferred embodiment of the invention, the printing method of step (a) is screen printing.

於本發明之一較佳實施例中,該步驟(a)之導電溶液為貴金屬溶液,特別為銀膠溶液。In a preferred embodiment of the present invention, the conductive solution of the step (a) is a precious metal solution, particularly a silver paste solution.

於本發明之一較佳實施例中,該步驟(a)之電極圖案為指叉式電極。In a preferred embodiment of the present invention, the electrode pattern of the step (a) is an interdigitated electrode.

於本發明之一較佳實施例中,該步驟(a)之紙基板之材質為濾紙。In a preferred embodiment of the present invention, the material of the paper substrate of the step (a) is a filter paper.

於本發明之一較佳實施例中,該步驟(b)之膠粘劑係透過UV燈固化。In a preferred embodiment of the invention, the adhesive of step (b) is cured by means of a UV lamp.

於本發明之一較佳實施例中,該步驟(d)之吸收層之材質為無塵紙。In a preferred embodiment of the present invention, the material of the absorption layer of the step (d) is a dust-free paper.

本發明之另一技術手段在於提供一種應用於生物檢測晶片之具三維流道紙基板感測器,包含︰一吸收層,該吸收層包含一無塵紙,用以吸收多餘檢體;一傳感層,以親水膠結合於該吸收層,並包含一紙基板,位於該紙基板上印刷有電極圖案,且於該紙基板上方結合有膠粘劑,並使該膠粘劑固化而形成疏水區域,位於該電極圖案表面修飾有抗體奈米粒子;以及一運輸層,以親水膠結合於該傳感層,並包含一濾紙,位於該濾紙上方結合有膠粘劑,並使該膠粘劑固化而形成疏水區域及一流道,而能藉該流道運輸檢體。Another technical means of the present invention is to provide a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer, comprising: an absorbing layer, the absorbing layer comprising a dust-free paper for absorbing excess sample; The layer is bonded to the absorbing layer by a hydrophilic glue, and comprises a paper substrate on which an electrode pattern is printed, and an adhesive is bonded on the paper substrate, and the adhesive is cured to form a hydrophobic region at the electrode. The surface of the pattern is modified with antibody nano particles; and a transport layer is bonded to the sensing layer by a hydrophilic glue, and comprises a filter paper, an adhesive is disposed on the filter paper, and the adhesive is solidified to form a hydrophobic region and a first-class track. The specimen can be transported by the runner.

於本發明之一較佳實施例中,該紙基板為濾紙。In a preferred embodiment of the invention, the paper substrate is a filter paper.

於本發明之一較佳實施例中,該電極圖案係透過將銀膠溶液以網版印刷方式成型。In a preferred embodiment of the invention, the electrode pattern is formed by screen printing a silver paste solution.

於本發明之一較佳實施例中,該膠粘劑係透過UV燈固化。In a preferred embodiment of the invention, the adhesive is cured by a UV lamp.

基於上述,使運用本發明所提供之技術手段製作之紙基材感測器具有三維流道,且能透過運輸層及傳感層使檢測電極與參考電極同時反應,再搭配分析儀讀取檢測數據,而能於運算阻抗數值後推算其反應程度,以完成生物材料免疫分析檢測。Based on the above, the paper substrate sensor manufactured by using the technical means provided by the invention has a three-dimensional flow channel, and the detection electrode and the reference electrode can be simultaneously reacted through the transport layer and the sensing layer, and then read and detected by the analyzer. Data, and the degree of reaction can be calculated after calculating the impedance value to complete the biological material immunoassay.

為使  貴審查委員瞭解本發明欲達成目的所運用之技術、手段及功效,茲舉一較佳實施例並配合圖式,詳細說明如后︰In order to make the reviewers aware of the techniques, means and effects of the present invention in order to achieve the objectives, a preferred embodiment will be described in detail with reference to the drawings.

首先,請參閱第1-A~1-B圖所示,係本發明感測器製作之流程圖,包含下列步驟︰First, please refer to the figure 1-A~1-B, which is a flow chart of the sensor manufacturing of the present invention, comprising the following steps:

於本實施例中,其感測器1包含一傳感層11、一運輸層12及一吸收層13;而該感測器1製作上,(步驟S1)係選用具適當孔洞大小之濾紙作為印刷紙基板111,再藉由網版印刷技術將導電溶液印刷於紙基板111以形成具特定形狀之電極圖案112,較佳者,該導電溶液為貴金屬溶液,特別為銀膠溶液。而其電極圖案112為指叉式電極,並以左右兩邊呈梳狀排列。接著,(步驟S2)於紙基板111噴塗適量紫外線膠粘劑113,並使膠粘劑113穿透紙張深度,再透過照射UV燈使膠體固化而能遮蔽特定區域並於紙基板111形成疏水區域;且於另一濾紙121噴塗適量紫外線膠粘劑122,並同樣透過UV燈使膠體固化,使濾紙121具有疏水區域,並使濾紙121未噴塗膠體之部分形成一流道123,以構成運輸層12。(步驟S3)位於電極圖案112表面修飾可結合待檢測分子之抗體奈米粒子114以構成一傳感層11。(步驟S4)以親水膠依序將傳感層11及運輸層12貼合於一吸收層13,以藉吸收層13吸收多餘檢體;並構成一紙基板感測器1(步驟S5)。且能將該感測器1封裝於一具窗口21之殼體2(配合參閱第2圖),並於殼體2與感測器1之間設一過濾層3。In this embodiment, the sensor 1 includes a sensing layer 11, a transport layer 12 and an absorbing layer 13; and the sensor 1 is fabricated, (step S1) is selected as a filter material of a suitable hole size. The printed paper substrate 111 is printed on the paper substrate 111 by a screen printing technique to form an electrode pattern 112 having a specific shape. Preferably, the conductive solution is a precious metal solution, particularly a silver paste solution. The electrode pattern 112 is an interdigitated electrode and is arranged in a comb shape on both left and right sides. Next, (step S2) spraying an appropriate amount of the ultraviolet adhesive 113 on the paper substrate 111, and allowing the adhesive 113 to penetrate the depth of the paper, and then curing the colloid by irradiating the UV lamp to cover a specific region and form a hydrophobic region on the paper substrate 111; A filter paper 121 is sprayed with an appropriate amount of the ultraviolet adhesive 122, and the colloid is also solidified by the UV lamp, so that the filter paper 121 has a hydrophobic region, and the portion of the filter paper 121 not sprayed with the gel forms a channel 123 to constitute the transport layer 12. (Step S3) The surface of the electrode pattern 112 is modified to bind the antibody nanoparticles 114 to be detected to form a sensing layer 11. (Step S4) The sensing layer 11 and the transport layer 12 are sequentially attached to an absorbing layer 13 with a hydrophilic gel to absorb the excess sample by the absorbing layer 13; and a paper substrate sensor 1 is constructed (step S5). The sensor 1 can be packaged in a housing 2 with a window 21 (refer to FIG. 2), and a filter layer 3 is disposed between the housing 2 and the sensor 1.

基於上述技術手段,使所製成之感測器1藉由疏水區域形成可快速運輸檢體至檢測區之流道123(配合參閱第3圖),並透過使傳感層11之印刷電極圖案112形成之檢測區115與參考區116同時反應,且搭配分析儀4以量測免疫分析前、後之阻抗值變化量,藉此完成生物材料免疫分析檢測。Based on the above technical means, the prepared sensor 1 forms a flow path 123 capable of quickly transporting the sample to the detection area by the hydrophobic region (refer to FIG. 3), and transmits the printed electrode pattern of the sensing layer 11 The detection zone 115 formed by 112 and the reference zone 116 are simultaneously reacted, and the analyzer 4 is used to measure the change of the impedance value before and after the immunoassay, thereby completing the biomaterial immunoassay detection.

由於近年來慢性腎臟病之盛行率於世界各國有逐年攀升的趨勢,且於本國有約九成以上患者不知自身罹患此病而延誤治療,因此,本發明之一研究實驗係將感測器1設計應用於尿液中蛋白質含量檢測。於此項實驗中,本發明係使用尺寸1微米之聚苯胺生物微米探針(PANI MPs),利用氧化還原方式將氧化鋁(Al 2O 3)粒子表面包覆導電性聚苯胺(PANDB)材料,以矽烷官能基修飾粒子表面以供抗體鍵結形成探針並擔任生物識別元件,而無鍵結抗體之探針則作為對照,並分別將有鍵結抗體及無鍵結抗體之探針修飾於檢測區115及參考區116表面(配合參閱第4-A~4-B圖)。於此實驗中,本發明採用蛋白質溶液為檢體5滴入感測器1,使檢體5經由過濾層3緩衝後,由流道123導引至檢測區115及參考區116。透過生物抗體與蛋白質之間產生免疫分析反應後,所反應的蛋白質溶液中,抗原會與抗體產生自組性相嫁接現象,而能搭配市售阻抗分析儀4(LCR Meter)來讀取檢測數據,並於運算阻抗數值後推算其反應程度,以完成生物材料免疫分析檢測。其運算方式係透過阻抗變化率公式計算即[(免疫反應後-免疫反應前)/免疫反應前],以得知反應過程中感測器1之變化率。實驗結果顯示(配合參閱第5圖),本發明之感測器1有鍵結抗體的阻抗數值明顯高於無鍵結抗體的阻抗數值,且二者差異達2.1倍,證明本發明之感測器1確實能分辨出感測檢體5中,其免疫分析的差別。 Since the prevalence of chronic kidney disease has been increasing year by year in various countries in the world, and more than 90% of patients in the country do not know that they suffer from this disease and delay treatment, therefore, one of the research experiments of the present invention will be the sensor 1 Designed for use in the detection of protein in urine. In this experiment, the present invention uses a 1 micron size polyaniline biomicron probe (PANI MPs) to coat the surface of alumina (Al 2 O 3 ) particles with a conductive polyaniline (PANDB) material by redox. The surface of the particle is modified with a decane functional group for antibody binding to form a probe and serves as a biorecognition element, while the probe of the unbound antibody is used as a control, and the probe with the bound antibody and the unbound antibody is respectively modified. On the surface of the detection area 115 and the reference area 116 (refer to Figures 4-A to 4-B). In this experiment, the present invention uses a protein solution to drop the sample 5 into the sensor 1, and after the sample 5 is buffered via the filter layer 3, it is guided by the flow path 123 to the detection area 115 and the reference area 116. After an immunoassay reaction between the biological antibody and the protein, the antigen will be self-assembled with the antibody in the reacted protein solution, and the detection data can be read by using a commercially available impedance analyzer 4 (LCR Meter). And calculate the degree of reaction after calculating the impedance value to complete the biological material immunoassay. The calculation method is calculated by the equation of the impedance change rate, ie [(before the immune reaction - before the immune reaction) / before the immune reaction], to know the rate of change of the sensor 1 during the reaction. The experimental results show that (in conjunction with FIG. 5), the impedance value of the bonded antibody of the sensor 1 of the present invention is significantly higher than that of the unbound antibody, and the difference between the two is 2.1 times, which proves the sensing of the present invention. The device 1 can indeed distinguish the difference in immunoassay in the sensing sample 5.

是以,透過本發明之技術手段製作之紙基板感測器1,顯然能達成如下之功效︰ 1.     本發明係依序透過以疏水區域界定供運輸檢體5之流道123的運輸層12、利用網印技術印製指叉狀之銀微電極圖案112,而能用於量測免疫分析前後之阻抗值變化量的傳感層11,以及能將多餘檢體5快速吸收之吸收層13,使所構成之感測器1能利用特定蛋白與抗體間形成複合物,並以電阻值之變化來達到定量檢測與快速篩檢之目的。 2.     本發明之感測器1能配合生物免疫反應機制使其能應用於多種檢測領域,並具有多功能性、快速、高靈敏度及低成本等優點,而能用於臨床與化學分析及疾病檢測、食安問題、農藥殘留、流感病毒或是毒品篩檢…等其它檢測領域。 3.     本發明選用無塵紙材質作為吸收層13,而能於感測時快速將多餘檢體5吸乾,使阻抗值能在短時間內穩定,有效的降低反映過程時間,並有助於後續數據量測。 4.     本發明之傳感層11係利用網印技術取代傳統黃光微影製程,以藉此提高生產效率,並降低生產晶片之成本。 5.     本發明之運輸層12於係採用可透過UV光固化之膠粘劑113(122)噴塗技術,成功的將濾紙圖案化而分別形成親疏水區域,且圖案化後之濾紙表面膜厚均勻,有利於後續實驗之進行。Therefore, the paper substrate sensor 1 manufactured by the technical means of the present invention can obviously achieve the following effects: 1. The present invention sequentially passes through the transport layer 12 defining the flow path 123 for transporting the sample 5 with a hydrophobic region. The fingerprint layer 11 for printing the interdigitated silver microelectrode pattern 112 by screen printing technology, and the sensing layer 11 capable of measuring the change in the impedance value before and after the immunoassay, and the absorption layer 13 capable of rapidly absorbing the excess sample 5 The sensor 1 can be used to form a complex between a specific protein and an antibody, and the resistance value is used to achieve quantitative detection and rapid screening. 2. The sensor 1 of the invention can be applied to various detection fields in combination with a biological immune reaction mechanism, and has the advantages of versatility, rapidity, high sensitivity and low cost, and can be used for clinical and chemical analysis and diseases. Other testing areas such as testing, food safety problems, pesticide residues, influenza viruses or drug screening... 3. The invention adopts the dust-free paper material as the absorbing layer 13, and can quickly dry the excess sample 5 during sensing, so that the impedance value can be stabilized in a short time, effectively reducing the reflection process time, and contributing to the subsequent Data measurement. 4. The sensing layer 11 of the present invention replaces the conventional yellow light lithography process by screen printing technology, thereby increasing production efficiency and reducing the cost of producing wafers. 5. The transport layer 12 of the present invention uses a UV-curable adhesive 113 (122) spraying technique to successfully pattern the filter paper to form a hydrophilic and hydrophobic region, and the patterned filter paper has a uniform film thickness. In the follow-up experiment.

惟以上所述者,僅為本發明之較佳實施例,並非用以限定本發明之實施範圍,凡未脫離本發明技藝精神所為之變化與修飾,皆為本發明專利範圍所涵蓋。The above is only the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention, and variations and modifications thereof are not included in the scope of the present invention.

綜上所述,本發明確實已突破傳統並具有改良及創新之創作內容且能具體實施,理應符合發明專利之法定要件,爰依法提出專利申請,懇請 鈞局審查委員授予合法專利權,以勵創作,至感德便。In summary, the present invention has indeed broken through the tradition and has improved and innovative creation content and can be specifically implemented, which should meet the statutory requirements of the invention patent, and file a patent application according to law, and invite the examination committee of the bureau to grant legal patent rights. Creation, to the sense of virtue.

本發明︰
S1~S5 步驟
1‧‧‧感測器
11‧‧‧傳感層
111‧‧‧紙基板
112‧‧‧電極圖案
113‧‧‧膠粘劑
114‧‧‧抗體奈米粒子
115‧‧‧檢測區
116‧‧‧參考區
12‧‧‧運輸層
121‧‧‧濾紙
122‧‧‧膠粘劑
123‧‧‧流道
13‧‧‧吸收層
2‧‧‧殼體
21‧‧‧窗口
3‧‧‧過濾層
4‧‧‧分析儀
5‧‧‧檢體
this invention︰
S1~S5 Step 1‧‧‧Sensor 11‧‧‧Sensor layer 111‧‧‧paper substrate 112‧‧‧electrode pattern 113‧‧‧Adhesive 114‧‧‧Antibody nanoparticles 115‧‧‧Detection area 116 ‧ ‧ Reference area 12 ‧ ‧ transport layer 121 ‧ ‧ filter paper 122 ‧ ‧ adhesive 123 ‧ ‧ flow path 13 ‧ ‧ absorbent layer 2 ‧ ‧ housing 21 ‧ ‧ window 3 ‧ ‧ filter layer 4‧‧‧Analyzer 5‧‧‧

第1-A~1-B圖係本發明感測器製作之流程圖。 第2圖係本發明感測器封裝之流程圖。 第3圖係本發明感測器檢測之示意圖。 第4-A~4-B圖係本發明感測器免疫分析之示意圖。 第5圖係本發明感測器免疫分析結果之曲線圖。Figures 1-A~1-B are flow charts for the fabrication of the sensor of the present invention. Figure 2 is a flow chart of the sensor package of the present invention. Figure 3 is a schematic illustration of the sensor detection of the present invention. Figures 4-A to 4-B are schematic views of the immunoassay of the sensor of the present invention. Fig. 5 is a graph showing the results of immunoassay of the sensor of the present invention.

1‧‧‧感測器 1‧‧‧ sensor

11‧‧‧傳感層 11‧‧‧ sensing layer

112‧‧‧電極圖案 112‧‧‧electrode pattern

115‧‧‧檢測區 115‧‧‧Detection area

116‧‧‧參考區 116‧‧‧Reference area

123‧‧‧流道 123‧‧‧ flow path

3‧‧‧過濾層 3‧‧‧Filter layer

4‧‧‧分析儀 4‧‧‧Analyzer

5‧‧‧檢體 5‧‧‧Check

Claims (10)

一種應用於生物檢測晶片之具三維流道紙基板感測器製造方法,包含下列步驟︰ (a)   將導電溶液印刷於一紙基板以形成具特定形狀之電極圖案; (b)   分別於該紙基板及一濾紙噴塗膠粘劑,並使膠體固化,而於該紙基板及該濾紙形成疏水區域,使該濾紙具有一流道而構成運輸層; (c)    於該電極圖案表面修飾可結合待檢測分子之抗體奈米粒子以構成一傳感層; (d)   以親水膠依序將該傳感層及該運輸層貼合於一吸收層;以及 (e)   構成一紙基板感測器。A method for manufacturing a three-dimensional flow path paper substrate sensor applied to a bio-detection wafer comprises the following steps: (a) printing a conductive solution on a paper substrate to form an electrode pattern having a specific shape; (b) respectively on the paper The substrate and a filter paper are sprayed with the adhesive, and the colloid is solidified, and the paper substrate and the filter paper form a hydrophobic region, so that the filter paper has a first-class track to constitute a transport layer; (c) the surface of the electrode pattern is modified to bind the molecule to be detected. The antibody nanoparticles are configured to form a sensing layer; (d) the sensing layer and the transport layer are sequentially attached to an absorbent layer with a hydrophilic gel; and (e) constitute a paper substrate sensor. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(a)之印刷方式為網版印刷。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the printing method of the step (a) is screen printing. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(a)之導電溶液為銀膠溶液。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the conductive solution of the step (a) is a silver paste solution. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(a)之電極圖案為指叉式電極。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the electrode pattern of the step (a) is an interdigitated electrode. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(a)之紙基板之材質為濾紙。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the material of the paper substrate of the step (a) is a filter paper. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(b)之膠粘劑係透過UV燈固化。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the adhesive of the step (b) is cured by a UV lamp. 如請求項1所述之應用於生物檢測晶片之具三維流道紙基板感測器製造方法,其中,該步驟(d)之吸收層之材質為無塵紙。The method for manufacturing a three-dimensional flow path paper substrate sensor for use in a bio-detection wafer according to claim 1, wherein the material of the absorption layer of the step (d) is a dust-free paper. 一種應用於生物檢測晶片之具三維流道紙基板感測器,包含︰ 一吸收層,該吸收層包含一無塵紙,用以吸收多餘檢體; 一傳感層,以親水膠結合於該吸收層,並包含一紙基板,位於該紙基板上印刷有電極圖案,且於該紙基板上方結合有膠粘劑,並使該膠粘劑固化而形成疏水區域,位於該電極圖案表面修飾有抗體奈米粒子;以及 一運輸層,以親水膠結合於該傳感層,並包含一濾紙,位於該濾紙上方結合有膠粘劑,並使該膠粘劑固化而形成疏水區域及一流道,而能藉該流道運輸檢體。A three-dimensional flow path paper substrate sensor for use in a bio-detection wafer, comprising: an absorbing layer comprising a dust-free paper for absorbing excess sample; a sensing layer bonded to the absorption by a hydrophilic glue a layer comprising a paper substrate on which an electrode pattern is printed, and an adhesive is bonded over the paper substrate, and the adhesive is cured to form a hydrophobic region, and the surface of the electrode pattern is modified with antibody nano particles; And a transport layer, which is bonded to the sensing layer by a hydrophilic glue, and comprises a filter paper, and an adhesive is disposed on the filter paper, and the adhesive is solidified to form a hydrophobic region and a first-class track, and the sample can be transported by the flow channel . 如請求項8所述之應用於生物檢測晶片之具三維流道紙基板感測器,其中,該紙基板為濾紙。A three-dimensional flow path paper substrate sensor for use in a biodetection wafer according to claim 8, wherein the paper substrate is a filter paper. 如請求項8所述之應用於生物檢測晶片之具三維流道紙基板感測器,其中,該膠粘劑係透過UV燈固化。A three-dimensional flow path paper substrate sensor for use in a bioassay wafer according to claim 8, wherein the adhesive is cured by a UV lamp.
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