TWI849643B - Improved structure of quantitative molecular detection chip - Google Patents
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Abstract
本發明係揭露一種定量分子檢測晶片之改良結構,其主要係包括一基部、一反應槽及一透光部,其中,該反應槽係設於該基部上,用以容置一待測物;該透光部係具有一與該反應槽相隔開來之曲面,並使該曲面的光學聚焦點位於該反應槽之槽空間範圍內,據以使一光線經過該曲面後,可將該光線聚焦於該反應槽中。 The present invention discloses an improved structure of a quantitative molecular detection chip, which mainly includes a base, a reaction tank and a light-transmitting portion, wherein the reaction tank is arranged on the base to accommodate a test object; the light-transmitting portion has a curved surface separated from the reaction tank, and the optical focus point of the curved surface is located within the tank space range of the reaction tank, so that a light ray can be focused in the reaction tank after passing through the curved surface.
Description
本發明係與生物晶片技術有關,特別是關於一種定量分子檢測系統、定量分子檢測晶片之改良結構及該晶片的製造方法。 The present invention is related to biochip technology, in particular to a quantitative molecular detection system, an improved structure of a quantitative molecular detection chip and a method for manufacturing the chip.
按,生物晶片(biochip)係藉由微機電技術進行生物性反應或分析,例如,基因表現分析、疾病診斷、篩檢藥物、基因定序、蛋白質分析等。而生物晶片檢測的方式種類眾多,譬如光學光譜偵測、電化學偵測、質譜分析法等,其中,針對光學光譜偵測,主要係以特定波長之光線來照射待測樣品,以接收經激發的散射光或反射光、並進行分析。 According to the microelectromechanical technology, biochips are used to perform biological reactions or analyses, such as gene expression analysis, disease diagnosis, drug screening, gene sequencing, protein analysis, etc. There are many types of biochip detection methods, such as optical spectroscopy, electrochemical detection, mass spectrometry, etc. Among them, optical spectroscopy mainly uses light of a specific wavelength to illuminate the sample to be tested, so as to receive the excited scattered light or reflected light and perform analysis.
然而,如前所述,現有技術中雖利用光學偵測的方式進行檢測,但其檢測效果不佳,絕大部分都是因為光學偵測對於散射或反射光之光波訊號強度較為敏感,若其強度稍有不足,將可能影響檢測結果的準確性。 However, as mentioned above, although the existing technology uses optical detection for detection, its detection effect is not good. Most of the reasons are that optical detection is more sensitive to the intensity of the light wave signal of scattered or reflected light. If the intensity is slightly insufficient, it may affect the accuracy of the detection result.
據此,如能在避免增加設備成本的考量下,即並未提高既有光源的發光強度的前提,如何提供一種可確保光波訊號的強度的檢測方法,將有待進一步改善與研發。 Based on this, how to provide a detection method that can ensure the intensity of light wave signals without increasing the cost of equipment, that is, without increasing the intensity of the existing light source, will require further improvement and research and development.
因此,本發明之主要目的係在於提供一種定量分子檢測晶片之改良結構,其係能夠將外部光源所發出的光線匯聚至該檢測晶片上之一待測區域中,以提高受激發的反射光的光波訊號強度,並改善習知技術檢測效果不佳的問題。 Therefore, the main purpose of the present invention is to provide an improved structure of a quantitative molecular detection chip, which can focus the light emitted by an external light source into a test area on the detection chip to increase the light wave signal intensity of the stimulated reflected light and improve the problem of poor detection effect of the known technology.
緣是,為達成上述目的,本發明所提供的定量分子檢測晶片之改良結構,其主要係包括一基部、一反應槽及一透光部,其中,該反應槽係設於該基部上,用以容置一待測物;該透光部係具有一與該反應槽相隔開來之曲面,並使該曲面的光學聚焦點位於該反應槽之槽空間範圍內,據以使一光線經過該曲面後,可將該光線聚焦於該反應槽中。 Therefore, in order to achieve the above-mentioned purpose, the improved structure of the quantitative molecular detection chip provided by the present invention mainly includes a base, a reaction tank and a light-transmitting portion, wherein the reaction tank is arranged on the base to accommodate a test object; the light-transmitting portion has a curved surface separated from the reaction tank, and the optical focusing point of the curved surface is located within the tank space range of the reaction tank, so that a light ray can be focused in the reaction tank after passing through the curved surface.
在一實施例中,該反應槽槽壁與槽底係形成有一第一親水性表面,以避免該待測物置入該反應槽之際產生氣泡,而影響反應溫度的均勻性、光學偵測準確性、或導致漏液。 In one embodiment, the reaction tank wall and the bottom are formed with a first hydrophilic surface to prevent the generation of bubbles when the test object is placed in the reaction tank, thereby affecting the uniformity of the reaction temperature, the accuracy of optical detection, or causing leakage.
在一實施例中,該第一親水性表面係以電漿處理所形成。 In one embodiment, the first hydrophilic surface is formed by plasma treatment.
在一實施例中,該透光部之曲面係形成於該基部外圍輪廓表面上。 In one embodiment, the curved surface of the light-transmitting portion is formed on the outer peripheral contour surface of the base.
在一實施例中,該透光部與該基部係一體成形。 In one embodiment, the light-transmitting portion and the base are integrally formed.
在一實施例中,該曲面係以該反應槽的中心作為光學聚焦點。 In one embodiment, the curved surface uses the center of the reaction tank as the optical focal point.
在一實施例中,該反應槽係呈圓管狀,並使圓管之曲率中心係作為該曲面之光學聚焦點。 In one embodiment, the reaction tank is in the shape of a circular tube, and the center of curvature of the circular tube is used as the optical focusing point of the curved surface.
在一實施例中,該基部係具有一第一側,並使該反應槽之槽口位於該第一側上,而本發明更包含有一封裝部,係設於該基部之該第一側上,以封閉該反應槽的槽口。 In one embodiment, the base has a first side, and the notch of the reaction tank is located on the first side, and the present invention further includes a packaging part, which is arranged on the first side of the base to close the notch of the reaction tank.
在一實施例中,該封裝部包括一膜層及一第一膠層,其中,該膜層係覆於該基部之該第一側上;該第一膠層係介於該膜層與該基部之間,以將該膜層黏合於該基部上。 In one embodiment, the packaging portion includes a film layer and a first adhesive layer, wherein the film layer covers the first side of the base; the first adhesive layer is between the film layer and the base to bond the film layer to the base.
在一實施例中,該基部具有一板體,而該板體具有一板身、一第一側、一第二側、一注入凹孔、一注入流道、一流出凹孔及一流出流道,而該第一側與該第二側分別位於該板身上兩相背之端面,且該反應槽係凹設於該板身之該第一側上,該注入凹孔係與該反應槽相隔開來地凹設於該板身之該第一側上,並於該注入凹孔與該反應槽之間設有該注入流道,藉以連通該注入凹孔與該反應槽,而該流出凹孔係遠離該注入凹孔所在位置並與該反應槽相隔開來地凹設於該板體之該第一側上,並於該流出凹孔與該反應槽之間設有該流出流道,藉以連通該流出凹孔與該反應槽。 In one embodiment, the base has a plate body, and the plate body has a plate body, a first side, a second side, an injection concave hole, an injection flow channel, an outflow concave hole and an outflow flow channel, and the first side and the second side are respectively located on two opposite end surfaces of the plate body, and the reaction tank is recessed on the first side of the plate body, and the injection concave hole is recessed on the plate body to be separated from the reaction tank. The injection concave hole is disposed on the first side of the plate body, and the injection channel is disposed between the injection concave hole and the reaction tank to connect the injection concave hole and the reaction tank, and the outflow concave hole is disposed on the first side of the plate body away from the injection concave hole and separated from the reaction tank, and the outflow channel is disposed between the outflow concave hole and the reaction tank to connect the outflow concave hole and the reaction tank.
在一實施例中,該封裝部包括一座體、一第一流道及一第二流道,其中,該第一流道及一第二流道係分別對應該注入凹孔與該流出凹孔之所在位置貫設於該座體上,且該第一流道內壁面及一第二流道內壁面係分別形成有一第二親水性表面;據此,當該座體設於該基部之該第一側上時,係使該第一流道及一第二流道分別與該注入凹孔與該流出凹孔對接且相連通。 In one embodiment, the packaging part includes a base, a first flow channel and a second flow channel, wherein the first flow channel and the second flow channel are respectively arranged on the base corresponding to the positions of the injection concave hole and the outflow concave hole, and the inner wall surface of the first flow channel and the inner wall surface of the second flow channel are respectively formed with a second hydrophilic surface; accordingly, when the base is arranged on the first side of the base, the first flow channel and the second flow channel are respectively connected to and communicated with the injection concave hole and the outflow concave hole.
在一實施例中,該第二親水性表面係以電漿處理所形成。 In one embodiment, the second hydrophilic surface is formed by plasma treatment.
在一實施例中,該封裝部更包括一第二膠層,係介於該座體與該基部之間,以將該座體黏合於該基部上。 In one embodiment, the packaging portion further includes a second adhesive layer between the seat and the base to bond the seat to the base.
在一實施例中,該封裝部更包括一塞體,可拆卸地嵌設於該流道遠離該基部而於該座體一端側所開設之一開口中,以封閉該流道與外界之連通。 In one embodiment, the packaging part further includes a plug body, which is detachably embedded in an opening opened at one end of the base body away from the flow channel to seal the connection between the flow channel and the outside.
在一實施例中,該基部係具有相背於該第一側之一第二側;而本發明更包含有一溫度調節部及一感測部,其中,該溫度調節部係對應該反應槽的位置而設於該基部之該第二側上,以對該反應槽中所容置的該待測物進行溫度調控;該感測部係與該溫度調節部電性連接,並鄰近於該溫度調節部的位置上。 In one embodiment, the base has a second side opposite to the first side; and the present invention further includes a temperature adjustment portion and a sensing portion, wherein the temperature adjustment portion is disposed on the second side of the base corresponding to the position of the reaction tank to adjust the temperature of the object to be tested contained in the reaction tank; the sensing portion is electrically connected to the temperature adjustment portion and is located adjacent to the temperature adjustment portion.
在一實施例中,該溫度調節部與該感測部係設於一本體上,並分別以一回饋電路與一處理部電性連接,而該處理部係接收該感測部所偵測出的訊號,藉以控制該溫度調節部之運作。 In one embodiment, the temperature adjustment part and the sensing part are arranged on a body and are electrically connected to a processing part via a feedback circuit respectively, and the processing part receives the signal detected by the sensing part to control the operation of the temperature adjustment part.
在一實施例中,該溫度調節部具有一平面加熱降溫迴圈,係配合該反應槽的形狀設置於該本體上與該反應槽重疊的區域中。 In one embodiment, the temperature regulating part has a planar heating and cooling loop, which is arranged in the area overlapping the reaction tank on the body in accordance with the shape of the reaction tank.
在一實施例中,該感測部具有一溫度感測點,對應該反應槽所在位置設於該本體上,且該加熱線圈係圍繞於該溫度感測點。 In one embodiment, the sensing portion has a temperature sensing point, which is arranged on the main body corresponding to the location of the reaction tank, and the heating coil surrounds the temperature sensing point.
再者,本發明還提供一種定量分子檢測系統,其包括一機台、一如前所述之晶片、一光源、一影像擷取部及一散熱部,其中,該晶片係設於該機台上;該光源係設於該機台上,而該光源所產生之一入射光係照射於該晶片上之該反應槽;該影像擷取部係設於該機台上,並接收由該入射光所激發之一螢光;該散熱部係設於該機台鄰近該晶片的位置上,用以對該晶片進行降溫。 Furthermore, the present invention also provides a quantitative molecular detection system, which includes a machine, a chip as described above, a light source, an image capture unit and a heat sink, wherein the chip is disposed on the machine; the light source is disposed on the machine, and an incident light generated by the light source is irradiated on the reaction tank on the chip; the image capture unit is disposed on the machine and receives a fluorescent light excited by the incident light; the heat sink is disposed at a position of the machine adjacent to the chip to cool the chip.
此外,本發明更提供一種製造定量分子檢測晶片之方法,係包含有下述步驟:步驟A:取用如前述之該基部;步驟B:對該基部上所設之該反應槽的槽壁進行電漿處理,以形成一第一親水性表面;步驟C:取一貼片覆設於該基部上,而該貼片載有一溫度調節部,用以對該反應槽中所容置的該待測物進行加熱及降溫;步驟D:利用一封裝技術封閉該反應槽之槽口。 In addition, the present invention further provides a method for manufacturing a quantitative molecular detection chip, which includes the following steps: Step A: Take the base as described above; Step B: Perform plasma treatment on the wall of the reaction tank provided on the base to form a first hydrophilic surface; Step C: Take a patch and cover it on the base, and the patch carries a temperature regulating part to heat and cool the test object contained in the reaction tank; Step D: Use a packaging technology to seal the slot of the reaction tank.
在一實施例中,該封裝技術係以一膜層上形成有一第一膠層之一側貼覆於該基部上,以將該膜層黏合於該基部上,並藉以封閉該反應槽。 In one embodiment, the packaging technology is to form a first adhesive layer on a film layer and affix one side of the first adhesive layer to the base to bond the film layer to the base and thereby seal the reaction tank.
在一實施例中,該封裝技術係將一注液座設於該基部上,且該注液座具有一座體及一貫穿該座體之流道,當該座體設於該基部上時,係使該流道與該反應槽相連通;將一塞體嵌設於該流道中,以封閉該流道與外界之連通。 In one embodiment, the packaging technology is to set a liquid injection seat on the base, and the liquid injection seat has a seat body and a flow channel penetrating the seat body. When the seat body is set on the base, the flow channel is connected to the reaction tank; a plug body is embedded in the flow channel to close the connection between the flow channel and the outside.
在一實施例中,更對該流道內壁面進行電漿處理,以形成一第二親水性表面。 In one embodiment, the inner wall surface of the flow channel is further subjected to plasma treatment to form a second hydrophilic surface.
在一實施例中,當該座體設於該基部上時,係使一第二膠層介於該座體與該基部之間,以將該座體黏合於該基部上。 In one embodiment, when the base is disposed on the base, a second adhesive layer is interposed between the base and the base to bond the base to the base.
10:定量分子檢測晶片 10: Quantitative molecular detection chip
10A、10B:晶片 10A, 10B: Chip
11:基部 11: Base
111、111A:板體 111, 111A: Plate
1111:板身 1111: Board body
1112、1112A:第一側 1112, 1112A: First side
1113:第二側 1113: Second side
1115、1115A:注入凹孔 1115, 1115A: injection concave hole
1116、1116A:注入流道 1116, 1116A: Injection channel
1117、1117A:流出凹孔 1117, 1117A: outflow concave hole
1118、1118A:流出流道 1118, 1118A: Outflow channel
12:感應加熱降溫單元 12: Induction heating and cooling unit
121:本體 121:Entity
122:溫度調節部 122: Temperature control unit
123:感測部 123:Sensor unit
124:回饋電路 124: Feedback circuit
13、13A:封裝部 13, 13A: Packaging Department
131:膜層 131: Membrane layer
132:第一膠層 132: First adhesive layer
133:座體 133: Seat
1331:基板 1331: Substrate
1332:第一管件 1332: First pipe fitting
1333:第二管件 1333: Second pipe fitting
1334:第一通孔 1334: First through hole
1335:第二通孔 1335: Second through hole
134:第一流道 134: First flow channel
135:第二膠層 135: Second adhesive layer
136:第一塞體 136: First plug
137:第二流道 137: Second flow channel
138:第二塞體 138: Second plug
14、14A:反應槽 14, 14A: Reactor
15:透光部 15: Light-transmitting part
20、20B:處理部 20, 20B: Processing Department
30:機台 30: Machine
40:光源 40: Light source
50:影像擷取部 50: Image capture unit
60:散熱部 60: Heat dissipation part
圖1係本發明之第一實施例所提供之定量分子檢測晶片的立體組合圖。 Figure 1 is a three-dimensional assembly diagram of the quantitative molecular detection chip provided by the first embodiment of the present invention.
圖2係本發明之第一實施例之定量分子檢測晶片的立體分解圖。 Figure 2 is a three-dimensional exploded view of the quantitative molecular detection chip of the first embodiment of the present invention.
圖3係就圖1沿3-3剖面線之剖視圖。 Figure 3 is a cross-sectional view taken along section line 3-3 of Figure 1.
圖4係本發明之第一實施例的具體使用態樣之系統方塊圖。 Figure 4 is a system block diagram of a specific usage pattern of the first embodiment of the present invention.
圖5係本發明之第二實施例所提供之定量分子檢測晶片的立體組合圖。 Figure 5 is a three-dimensional assembly diagram of the quantitative molecular detection chip provided by the second embodiment of the present invention.
圖6係本發明之第二實施例所提供之定量分子檢測晶片的立體分解圖。 Figure 6 is a three-dimensional exploded view of the quantitative molecular detection chip provided by the second embodiment of the present invention.
圖7係就圖5沿7-7剖面線之剖視圖。 Figure 7 is a cross-sectional view taken along section line 7-7 of Figure 5.
圖8係本發明之第三實施例所提供之定量分子檢測系統的示意圖。 Figure 8 is a schematic diagram of the quantitative molecular detection system provided by the third embodiment of the present invention.
圖9係本發明之第三實施例所提供之定量分子檢測系統的系統方塊圖。 FIG9 is a system block diagram of the quantitative molecular detection system provided by the third embodiment of the present invention.
首先,請參閱圖1至圖3所示,係本發明之第一實施例中所提供的定量分子檢測晶片10,其主要乃係包括一基部11、一感應加熱降溫單元12、一封裝部13、一反應槽14及一透光部15。
First, please refer to Figures 1 to 3, which are the quantitative
該基部11具有一板體111,該板體111具有一板身1111、一第一側1112、一第二側1113、一注入凹孔1115、一注入流道1116、一流出凹孔1117及一流出流道1118,其中,該板身1111為硬質的塑膠材質,例如聚碳酸酯(Polycarbonate,PC),並呈透明型態,以允許可見光通過,而該第一側1112與該第二側1113分別位於該板身1111上兩相背之端面。
The
再者,該反應槽14係凹設於該板身1111之該第一側1112上,用以容置一待測物。進一步來說,本例之該反應槽14係呈圓管狀結構,而在其他可能的實施態樣中,該反應槽14的槽壁所圍繞的形狀可為其他任意之造型,例如矩形、菱形、多邊形等。
Furthermore, the
該注入凹孔1115係與該反應槽14相隔開來地凹設於該板身1111之該第一側1112上,並於該注入凹孔1115與該反應槽14之間設有該注入流道1116,藉以連通該注入凹孔1115與該反應槽14,而該流出凹孔1117係遠離該注入凹孔1115所在位置並與該反應槽14相隔開來地凹設於該板體111之該第一側1112上,且使該反應槽14介於該注入凹孔1115與該流出凹孔1117之間,並於該流出凹孔1117與該反應槽14之間設有該流出流道1118,藉以連通該流出凹孔1117與該反應槽14。
The injection
該感應加熱降溫單元12具有一本體121、一溫度調節部122、一感測部123及一回饋電路124,其中,該本體121係為具撓性之聚醯亞胺薄膜(Polyimide Film,PI)、並配合該板體111的外圍輪廓形狀來設計,且其厚度為0.025mm,而該本體121係貼覆於該板體111之該第二側1113上。該感測部123具有一溫度感測點,係對應該反應槽14所在位置設於該本體121上相向於該板體111之
一側。該溫度調節部122具有一平面加熱降溫迴圈,係配合該反應槽14的形狀設置於該本體121上相向於該板體111之一側、並位於與該反應槽14相重疊的區域中,並使該加熱線圈圍繞於該溫度感測點,換句話說,該平面加熱降溫迴圈以該溫度感測點為中心、分設有多個直徑介於8mm至10mm之間的同心圓,並且,該平面加熱迴圈係同時以T-type熱電偶原理對該反應槽14中所承載的該待測物進行溫度偵測。該回饋電路124係利用現有軟性線路製程設於該本體121上,並於該本體121一側形成有數個接腳,以將該溫度調節部122與該感測部123分別電性連接至一外部之處理部20,如圖4所示,而該處理部20係接收該感測部123所偵測出的溫度訊號,藉以控制該溫度調節部122之運作。並且,該回饋電路124的材料可為銅、康銅、銦錫氧化物、金屬、導電型的碳材或其組合,而本例係選用銅及康銅,並利用金屬融合接合技術(Eutectic Bonding)來整合該溫度調節部122與該感測部123,而該金屬融合接合技術為習知技術,故不再贅述。此外,該本體121設有該回饋電路124、該溫度調節部122與該感測部123的一側面更可再貼覆一層聚醯亞胺薄膜。
The inductive heating and
藉由前述說明,該感應加熱降溫單元12係作為一溫度感測溫控貼片來使用,而貼覆於該基部11上。
According to the above description, the inductive heating and
該封裝部13係呈透明型態、允許可見光通過,並包括一膜層131及一第一膠層132,其中,該膜層131係厚度0.05mm之聚合物薄膜,固著並覆於該板體111之該第一側1112上,以同時封閉該反應槽14、該注入凹孔1115、該注入流道1116、該流出凹孔1117及該流出流道1118。並容許待測物與反應試劑穿透輸入反應槽14。再者,該第一膠層132係厚度0.125mm之聚合物封膜,並覆蓋膜層131以將該膜層之注入孔封閉並提供光學透性。此外,該膜層131與該板體111之間的固定技術並不限於前述黏合方式,更可利用其他的固定方式如超音波熔封、膠封等達到同樣的效果。
The
並且,該反應槽14槽壁與槽底、該注入凹孔1115孔壁、該注入流道1116壁面、該流出凹孔1117孔壁及該流出流道1118壁面分別形成有一第一親水性表面。換句話說,該晶片用以供該待測物流經通過或儲存之用而相接觸的表面上均可設置有該第一親水性表面。其中,該第一親水性表面係以電漿處理所形成,且該電漿最佳實施例為氧氣電漿,次佳為氬氣電漿,而該基部11在電漿中的光與離子的作用下,其表面係產生自由基(Free Radicals),而自由基的活性很大,很容易與物質產生化學反應,因此可以作為媒介去接合其他的物質。具體來說,在未經電漿改質表面與該第一親水性表面的水接觸角測試結果如下表所示,其中,該第一親水性表面分別於第一條件及第二條件下進行改質,第一條件係指選用電壓100W、固定氧氣流量50sscm、及測試時間為5分鐘,而第二條件係指選用電壓200W、固定氧氣流量50sscm、及測試時間為15分鐘,由下表數據可知,該第一親水性表面在不同條件下的親水性均大幅優於未經電漿改質的其他表面。據此,當該待測物流經該第一親水性表面之際,係能避免氣泡產生,以維持反應溫度的均勻性、光學偵測準確性、或避免漏液等情形發生。
Furthermore, the wall and bottom of the
該透光部15係具有一與該反應槽14相隔開來之曲面,且該曲面係一體成形地形成於該板體111之外圍輪廓表面上,並使該曲面之光學聚焦點位於
該反應槽14之槽空間範圍內,當一光線經過該曲面後,係使該光線聚焦於該反應槽14中。進一步來說,該曲面更以該反應槽14的中心作為光學聚焦點,得使該光線匯聚於該反應槽14上。並且,該光線的光斑範圍能夠涵蓋該反應槽14周遭外圍至少5mm之區域。
The light-transmitting
據此,藉由上述結構說明,本發明定量分子檢測晶片10的具體製造步驟如下:步驟A:取如前述之該基部11;步驟B:對該基部11上所設之該反應槽14的槽壁進行電漿處理,以形成一第一親水性表面;步驟C:取呈該溫度感測加熱降溫貼片覆設於該基部11上,而該溫度感測加熱降溫貼片上係載有該溫度調節部122,用以對該反應槽14中所容置的該待測物進行加熱與藉由金屬迴圈之高導熱特性配合氣冷降溫;步驟D:利用一封裝技術封閉該反應槽14之槽口。其中,該封裝技術係以該膜層131上形成有該第一膠層132之一側貼覆於該基部11上,以將該膜層131黏合於該基部11上,並藉以封閉該反應槽14。
Accordingly, through the above structural description, the specific manufacturing steps of the quantitative
如圖5及圖7所示,係本發明之第二實施例,其所揭之晶片10A與第一實施例主要差異在於該封裝部13A係作為一注液座,具體來說,該該封裝部13A包括有一座體133、一第一流道134、一第二膠層135、一第一塞體136、一第二流道137及一第二塞體138,其中,該座體133具有一基板1331、一第一管件1332及一第二管件1333,該第一管件1332係對應該注入凹孔1115A所在位置、依其管軸垂直該基板1331的板面地穿設於該基板1331上之一側,並於該基板1331另一側開設有一與該第一管件1332內部空間相連通之第一通孔1334,而使該第一管件1332內部空間與該第一通孔1334共同定義出該第一流道134,而該第一通孔1334的孔徑大小相仿於該注入凹孔1115A的孔徑大小。再者,該第二管件1333係對應該流出
凹孔1117A所在位置、依其管軸垂直該基板1331的板面地穿設於該基板1331上之一側,並於該基板1331另一側開設有一與該第二管件1333內部空間相連通之第二通孔1335,而使該第二管件1333內部空間與該第二通孔1335共同定義出該第二流道137,而該第二通孔1335的孔徑大小相仿於該流出凹孔1117A的孔徑大小。
As shown in FIG. 5 and FIG. 7, the second embodiment of the present invention is disclosed. The main difference between the
並且,於該第一管件1332的內壁面與該第二管件1333的內壁面係分別形成有一第二親水性表面,而該第二親水性表面同樣以前述相同之電漿處理技術所形成。
Furthermore, a second hydrophilic surface is formed on the inner wall surface of the
再者,該第二膠層135係利用網印處理技術設於該基板1331上、並與該第一通孔1334及該第二通孔1335位在相同側。其中,所述網印處理係指使用網版遮罩的印刷技術,以進行精密圖案塗佈的網版印刷,例如,該第二膠層135係配合該反應槽14A的輪廓、而取用適當的數量,而將該第二膠層135間斷地設於該基板1331上。在其他可能的實施態樣中,該第二膠層135亦可設於該板體111A之該第一側1112A上位於該反應槽14A的周圍,同樣可以達到黏固該座體133與該板體111A之作用。此外,該座體133與該板體111A之間的固定技術並不限於前述黏合方式,更可利用其他的固定方式達到同樣的效果。
Furthermore, the second adhesive layer 135 is disposed on the substrate 1331 using screen printing technology and is located on the same side as the first through
接著,當該座體133設於該板體111A之該第一側1112A上時,係使該基板1331覆於該板體111A之該第一側1112A上,以同時封閉該反應槽14A、該注入流道1116A、及該流出流道1118A,並使該使該第一通孔1334及該第二通孔1335分別與該注入凹孔1115A孔口及該流出凹孔1117A孔口對接,以使該第一流道134與該注入凹孔1115A相連通,該第二流道137與該流出凹孔1117A相連通。此外,該第二膠層135係介於該座體133與該板體111A之間,以將該座體133黏合於該板體111A上。
Next, when the
據此,舉以實施灌注該待測物為例,以進行罐注該待測物灌注用之注射器,其注嘴係插接於插設之用的該座體133的該第一管件1332中,並使注
嘴與該第一管件1332間具有適當之密接程度,以確保所灌注之待測物不致產生不當之滲流,而使該待測物依序經由該第一流道134、該注入凹孔1115A及該注入流道1116A而進入該反應槽14A中。
Based on this, taking the implementation of the injection of the test object as an example, the nozzle of the syringe used for the injection of the test object is inserted into the
該第一塞體136係可拆卸地設於該第一管件1332遠離該板體111A之一端開口中,以封閉該第一流道134與外界之連通。
The
該第二塞體138係可拆卸地嵌設於該第二管件1333遠離該板體111A之一端開口中,以封閉該第二流道137與外界之連通。
The
更進一步來說,該第一管件1332及該第二管件1333係分別於內壁設有一止逆結構,而得與該第一塞體136與第二塞體138彼此嵌接,以增加該注入凹孔1115A及該流出凹孔1117A之封閉性。
Furthermore, the
此外,更可將第二實施例中所定義的該封裝部13A應用於第一實施例中所述之製造該定量分子檢測晶片中的封裝技術上,而進行另一型態的封裝作業。
In addition, the
如圖8及圖9所示,係本發明之第三實施例中所提供的定量分子檢測系統,乃係包括該晶片10B、該處理部20B、一機台30、一光源40、一影像擷取部50、及一散熱部60,其中,該光源40、該影像擷取部50、該散熱部60及該處理部20B彼此之間係由任何有線或無線媒體(例如:4G、5G、WIFI、藍芽、NFC、RFID等)直接或間接地進行訊號之傳送。
As shown in FIG8 and FIG9, the quantitative molecular detection system provided in the third embodiment of the present invention includes the
該機台30是作為承載其他構件之基礎結構,簡單來說,本例之該機台30主要係由四個板體相互組裝而成,用以設置該晶片10B、該光源40、影像擷取部50、該散熱部60及該處理部20B。
The
該晶片10B取自第一實施例或第二實施例中所述之定量分子檢測晶片,用以承載該待測物,本例之該待測物包含生物樣品及PCR試劑,其中,該生物樣品係指源自於人類或其他動物之生物體(Organism)、或其細胞或組織之
組分(Components)的樣品,例如血液(Blood)、血漿(Plasma)、血清(Serum)、尿液(Urine)、唾液(Saliva)或糞便(Feces)等。
The
再者,該生物樣品係以該PCR試劑來作螢光標記,而常用的螢光標記可為但不限於FAM、HEX、TET、TAMRA、Cy3、Cy5、Cy5.5、Texas Red、VIC、Yakima Yellow、BHQ-1、BHQ-2或BHQ-3,其中,FAM為綠光,HEX為黃光,TAMRA為紅光。而在本例係採用FAM進行螢光標記,且其受激發所產生的螢光為波峰在520nm之激發光綠光波段。 Furthermore, the biological sample is fluorescently labeled with the PCR reagent, and commonly used fluorescent labels may be but are not limited to FAM, HEX, TET, TAMRA, Cy3, Cy5, Cy5.5, Texas Red, VIC, Yakima Yellow, BHQ-1, BHQ-2 or BHQ-3, where FAM is green light, HEX is yellow light, and TAMRA is red light. In this example, FAM is used for fluorescent labeling, and the fluorescence generated by its excitation is the green light band of the excitation light with a peak at 520nm.
該光源40可為但不限於紅色、綠色、藍色或其他顏色任一者已知之任意之發光元件,在本例中,該光源40採用型號為VISHAY 78-VLDB1232G-08之發光二極(LED),且其所發出的光線為波長介於458nm至472nm之間的藍光,較佳地該藍光峰值為465nm。再者,當該藍光照設於該晶片10B時,其入射角可為任意角度,較佳為45°。接著,該待測物受激發所產生的螢光為波峰在520nm之激發光綠光波段,並被該影像擷取部50所獲取。特別的是,該藍光得以透過該曲面而匯聚至該反應槽中,以提高受激發的螢光的光波訊號強度,而改善習知技術檢測效果不佳的問題。此外,該藍光更可穿透該封裝部13而自該板體111之該第一側1112進入該反應槽14中。
The
該影像擷取部50可為但不限於電荷耦合元件(Charge Coupled Device,CCD)、互補性氧化金屬半導體(Complementary Metal-Oxide Semiconductor,CMOS)元件或其他種類的感光元件,用以接收該螢光,以產生一光波訊號,並傳輸至該處理部20B中。並且,該影像擷取部50與該晶片10B之間更設有一濾光片,用以通過特定波長光線,以排除其他外界干擾訊號。
The
該處理部20B係具有一或多個微處理器、中央處理單元(CPU)、計算裝置、微控制器、數位信號處理器、圖形處理單元(GPU)、其他類似之具運算功能的裝置或其群組之任何組合,並接收該光波訊號用以執行檢測分析,而
該檢測分析係以螢光檢測法進行,而在其他可能的實施方式中亦可為反射率量測法或吸收率檢測法等。
The
該散熱部60為一吹風裝置,固定地設置在鄰近該晶片10B的位置上,且該吹風裝置包含有一馬達與一被該馬達驅所動之風扇,而該風扇的出風方向朝向該晶片10B,而受該處理部20B所控制以對該晶片10B進行氣冷式降溫,例如,在控制熱循環由高溫變性溫度(Denature temperature)降至低溫黏合溫度(Annealing temperature)的過程中係啟動該風扇,直到該晶片10B的溫度降到設定之黏合溫度時即停止該風扇之運轉。
The
據此,本發明之定量分子檢測系統在實際應用上係能作為qPCR(Real-time polymerase chain reaction)檢測之用。儘管以上闡述參照用於特定應用之說明性實施例,但應理解所請求之發明並不侷限於該等實施例。熟習此項技術者通過閱讀本文中所提供之教示內容將認識到隨附申請專利範圍之範疇內之額外修改、應用及實施例。 Accordingly, the quantitative molecular detection system of the present invention can be used for qPCR (Real-time polymerase chain reaction) detection in practical applications. Although the above description refers to illustrative embodiments for specific applications, it should be understood that the claimed invention is not limited to such embodiments. Those skilled in the art will recognize additional modifications, applications, and embodiments within the scope of the attached patent application by reading the teachings provided herein.
10:定量分子檢測晶片 10: Quantitative molecular detection chip
111:板體 111: Board
121:本體 121:Entity
131:膜層 131: Membrane layer
14:反應槽 14: Reactor
15:透光部 15: Light-transmitting part
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| TW200424516A (en) * | 2001-11-16 | 2004-11-16 | Nippon Sheet Glass Co Ltd | Chip element for microchemical systems , and microchemical system using the chip element |
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