TWI226437B - Image display type biochip instrument - Google Patents

Image display type biochip instrument Download PDF

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Publication number
TWI226437B
TWI226437B TW92123648A TW92123648A TWI226437B TW I226437 B TWI226437 B TW I226437B TW 92123648 A TW92123648 A TW 92123648A TW 92123648 A TW92123648 A TW 92123648A TW I226437 B TWI226437 B TW I226437B
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Taiwan
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biochip
light
image
light source
imaging
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TW92123648A
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Chinese (zh)
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TW200508594A (en
Inventor
Jian-Hua Wang
Tz-Chiang Wu
Jian-He Juang
Tsung-Kai Juang
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Kaiwood Technology Co Ltd
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Publication of TW200508594A publication Critical patent/TW200508594A/en

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Abstract

The invented image display type biochip instrument at least contains the followings: a light source for emitting light beam; a collimating lens for making light beam emitted from light source form large-area parallel light that passes through the biochip to excite the fluorescent material on the biochip and to emit fluorescent light; a focus lens for focusing fluorescent light; a filter plate for removing the interference light wave; and a CCD camera for extracting image of the fluorescent light signal. The image extracted by CCD camera can be converted by an image converting apparatus into the data so as to become convenient for determining the fluorescent light intensity of each analyzed sample point. The image display type biochip instrument uses the collimating lens to make laser light source generate large-area laser-light excitation light source such that each sample point can receive high efficiency excitation light source. In addition, by using CCD camera, large-area fluorescent light image of biochip can be extracted quickly to perform the analysis such that the analysis time is dramatically reduced.

Description

1226437 五、發明說明(1) 發明所屬之技術領域 本發明係關於一種生物晶片讀取裝置,特 ' ΤΛ r _____η____1 ^ J τχ _ _ · 〜 ^ ' 斤】是一 用 CCD (Charge-Coupled Device,電荷耗合元株—種利 圖像後進行分析的裝置。 仃耦…牛)相機擷取 先前技術 目鈾已有許多分析工具或分析方法可用亦、 蛋白質等生物分子,但是這些分析方法在分、^核酸或 時,常常需耗費相當長的時間才能得知分析2量的樣品 分析大量樣品時,常因樣品數過多, ^。再者, 中完成,如此容易造成分析數據的誤差丁於^一次分析 蛋白質體方面的研究而言,常需同時進行^量J因體以及 的分析工具。 个敦所而,因此需要更有效率 生物晶片具有可同時分析大量樣品的優點, f ◊ 矚目。此種分析工具可以節省分析的人力物力,因此f文 面的應用潛力,例如找尋呈立 ,具有夕方 的表現機制’“藥物筛選研究基因 等。 袁疋作為^床檢驗工具 目則的生物晶片係以Dna曰η幺太、、☆ 致上如第一圖所示,首. 一日日 、、々丨L ’其偵測方式大 片)的表面放置許多被當作在一固體承載物(如坡片或矽晶 成DNA晶片(〇,一般這也、抓針的/知DNA片段(2)而形 因此被稱為DNA微陣列。二另二針(2^疋以陣列方式排列, 另一方面,在待測的未知DNA片段1226437 V. Description of the invention (1) The technical field to which the invention belongs The present invention relates to a bio-chip reading device, and particularly 'ΤΛ r _____ η ____ 1 ^ J τχ _ _ · ~ ^' Jin] is a CCD (Charge-Coupled Device, Charge consumable strains—devices that analyze images after they are used to extract images. Couplings ... cattle) There are many analysis tools or analysis methods available for cameras to capture uranium in the prior art. Proteins and other biomolecules are available, but these analysis methods are It is often necessary to take a considerable time to know the analysis of 2 samples. When analyzing a large number of samples, it is often caused by too many samples. In addition, it is completed in China, so it is easy to cause errors in the analysis data. For the analysis of proteomics in one analysis, it is often necessary to simultaneously analyze the factors and analysis tools. Therefore, the need for more efficient biochips has the advantage of being able to analyze a large number of samples at the same time. This kind of analysis tool can save the manpower and material resources for analysis, so it has potential for application in f-text, for example, to find a stand-up, with the performance mechanism of Xi Fang '"drug screening and research genes, etc." Taking DNA as η 幺, ☆, as shown in the first picture, first. Day, day, 々 丨 L 'its detection method is large) The surface is placed as a solid load (such as slope A piece of silicon or a silicon crystal is formed into a DNA chip (0, which is generally also called a DNA microarray by grasping the needle / known DNA fragment (2). Two other needles (2 ^ 疋 are arranged in an array, on the other hand , Unknown DNA fragment under test

$ 6頁 1226437 五、發明說明(2) (3) (Target MA,目標DNA)上標記上螢光標記分子。接著將 DNA晶片(1)與目楳DNA(3)進行雜交(Hybr idization),經過 清洗步驟,使DNA晶片(1 )上只留有與ΜΑ探針結合的ΜΑ片 段,再經過生物晶片儀的掃描’測定螢光標記分子被激發 出的螢光,即可得知分析結果。 為了能更快速而正確地得知分析結果,讀取生物晶片 分析結果的生物晶片儀,也吸引相當多的研究者投入。 目前最常見的生物晶片儀是使用雷射光作為激發光 源,並且利用光電倍增管作為光偵測器,其元件構成大致 上如第二圖所示。此種生物晶片儀(4 )係由_雷射光源(4 〇 ) 發出光束,此雷射光束通過聚焦透鏡(41),於分光鏡(Beam splitter) (42)上反射,再通過另一聚焦透鏡(43),到達待 測晶片(44 )表面’晶片(44 )上的螢光標記分子受到雷射 的激發而被基發出螢光(45),螢光(45)通過聚焦透 (43)、分光鏡(42)、聚焦透鏡(46),再通過濾波 (Filter) (47)濾除激發光源的光波,^ 電倍增管(—ltipller tube,PMT)(JU以 (48)將光訊號轉為電子訊號並將訊 i 增官 分析儀需對生物晶片上的所有樣一 ^,阳片陣列 光訊號,因此相當耗時。 ’ .、, 進仃知描讀取螢 另一種類型的生物曰U装 激發光源,並以高像素^ c ’疋利用寬頻譜的白光作為 此種生物晶片儀雖然毋泰 機擷取圖像後再進行分析。 母而對樣品點一一進行掃描,但是^$ 6 pages 1226437 5. Description of the invention (2) (3) (Target MA, target DNA) is labeled with a fluorescent label molecule. Next, the DNA wafer (1) is hybridized with the target DNA (3). After the washing step, the DNA wafer (1) is left with only the MA fragment bound to the MA probe, and then passed through the biochip instrument. Scan 'to measure the fluorescence emitted by the fluorescently labeled molecules, and you can get the analysis result. In order to obtain the analysis results more quickly and accurately, the biochip reader that reads the analysis results of biochips has attracted considerable investment from researchers. At present, the most common biochip instrument uses laser light as the excitation light source and photomultiplier tube as the light detector. Its component structure is roughly shown in the second figure. This biochip (4) is a light beam emitted by a laser source (40). This laser beam passes through a focusing lens (41), is reflected on a beam splitter (42), and then passes through another focus. The lens (43) reaches the surface of the wafer to be measured (44). The fluorescently labeled molecules on the wafer (44) are excited by the laser to emit fluorescence (45) by the base, and the fluorescence (45) passes through the focus (43) , Beam splitter (42), focusing lens (46), and then filter (47) to filter out the light waves of the excitation light source, ^ electric multiplier tube (-ltipller tube (PMT) (JU to (48) to convert the optical signal It is an electronic signal and the signal analyzer needs to analyze all the samples on the biochip, and the optical signals of the positive array are very time-consuming. U is equipped with an excitation light source, and uses high-resolution white light with a wide pixel ^ c '此种 as this kind of biochip. Although the image is not captured by a Thai machine for analysis. The sample points are scanned one by one, but ^

1226437 五、發明說明(3) 白光光源的激發效能較差,因此其分析靈敏度不如前述類 型的生物晶片儀。若希望提昇分析靈敏度,則仍需耗費相 當長的時間才能得到較高的螢光訊號值。 綜前所述,若能發展一種快速讀取生物晶片分析結果 的生物晶片儀,將使生物晶片分析系統的實用性大幅提 昇。 發明内容 本發明的目的之一為提供一種顯像式生物晶片儀,其 係以大面積的雷射光同時激發生物晶片上的樣品,並以大 鏡頭的CCD相機將訊號擷取為影像再進行分析,如此可達到 快速偵測的目的。 本發明之顯像式生物晶片儀,其至少包含:一光源, 其係用以發出光束;一準直透鏡(Collimating Lens), 其係使光源所發出之光束形成大面積的平行光,該平行光 通過生物晶片,可使生物晶片上之螢光物質被激發出螢 光;一聚焦透鏡,其係用以使螢光聚焦;一濾光片;其係 用以濾除干擾光波;以及一 CCD相機,其係用以將螢光訊號 擷取為影像。該CCD相機所擷取的影像可經由一影像數據轉 換裝置,將影像訊號轉為數據,以利判讀各分析樣品點的 螢光強度。 - 因為本發明之顯像式生物晶片儀係使用準直透鏡使雷 射光源產生大面積的雷射光激發光源,因此可以使各樣品 點同時接受到高效能的激發光源。此外,本發明之顯像式1226437 V. Description of the invention (3) The excitation efficiency of the white light source is poor, so its analytical sensitivity is not as good as the aforementioned type of biochip instrument. If you want to increase the sensitivity of the analysis, it still takes a considerable time to get a higher fluorescence signal value. In summary, if we can develop a biochip analyzer that can quickly read the results of biochip analysis, the utility of the biochip analysis system will be greatly improved. SUMMARY OF THE INVENTION One of the objects of the present invention is to provide an imaging biochip, which uses a large area of laser light to simultaneously excite a sample on a biochip, and uses a large lens CCD camera to capture the signal as an image for analysis. , So you can achieve the purpose of rapid detection. The imaging biochip of the present invention includes at least: a light source for emitting a light beam; and a collimating lens (Collimating Lens) for forming a large area of parallel light emitted by the light source, the parallel light Light passing through the biochip can cause fluorescent substances on the biochip to be excited into fluorescence; a focusing lens for focusing the fluorescence; a filter; it is used to filter out interference light waves; and a CCD Camera for capturing fluorescent signals as images. The image captured by the CCD camera can be converted into data through an image data conversion device to facilitate the interpretation of the fluorescence intensity of each analysis sample point. -Because the imaging biochip of the present invention uses a collimating lens to make the laser light source generate a large area of laser light excitation light source, each sample point can receive a high-efficiency excitation light source at the same time. In addition, the development type of the present invention

1226437 五、發明說明(4) ^物晶片儀,可以利用CCD相機,大面積而快速的擷取生物 晶片的螢光影像,再進行分析,因此可大幅降低分析時 間。 以下將配合圖式進一步說明本發明的實施方式,下述 所歹j舉的貫施例係用以闡明本發明,並非珣以限定本發明 之範圍,任何熟習此技藝者,在不脫離本發明之精神和範 圍内’當可做些許更動與潤飾,因此本創作之保護範圍當 視後附之申請專利範圍所界定者為準。 胃 _第三圖為本發明顯像式生物晶片儀(5 )之一種實施例。 第二圖所示之生物晶片陣列分析儀(5 )包含一光源(5 〇 ),其 係用以發出光束;一準直透鏡(5 1 ),其係使光源所發出之 光束形成大面積的平行光,該平行光通過生物晶片(52), 使生物晶片(5 2 )上之螢光物質被激發出螢光;一聚焦透鏡 (53) ’其係用以使螢光聚焦;一濾光片(54);其係用以渡 除干擾光波;一大鏡頭的CCD相機(55),其係用以將螢光〜訊 號擷取為影像;一承載平台(5 7 ),其係用以承載生物晶片 (52);以及一影像數據轉換裝置(56),其可將影像訊號轉 為數據,以利判讀各分析樣品點的螢光強度。 利用本發明之顯像式生物晶片儀分析生物晶片時,係 先將生物晶片置放於承載平台(57)上,進行分析時,雷射 光源(5 0 )發出光束,此光束經過準直透鏡(5丨)而形成大面 積的平行光,該平行光通過生物晶片(5 2 ),使生物晶片1226437 V. Description of the invention (4) The object wafer instrument can use a CCD camera to quickly and quickly capture fluorescent images of biological wafers for analysis, thus greatly reducing analysis time. The embodiments of the present invention will be further described below with reference to the drawings. The following examples are used to clarify the present invention and are not intended to limit the scope of the present invention. Any person skilled in the art will not depart from the present invention. Within the spirit and scope of 'can be changed and retouched slightly, so the scope of protection of this creation shall be determined by the scope of the attached patent application. Stomach _ The third figure is an embodiment of the imaging biochip (5) of the present invention. The biochip array analyzer (5) shown in the second figure includes a light source (50) for emitting a light beam; a collimating lens (51) for forming a large area of the light beam emitted by the light source Parallel light, which passes through the biochip (52), so that the fluorescent substance on the biochip (52) is excited to emit fluorescent light; a focusing lens (53) is used to focus the fluorescent light; a filter Film (54); it is used to get rid of interference light waves; a large lens CCD camera (55), which is used to capture the fluorescence ~ signal as an image; a bearing platform (57), which is used to It carries a biochip (52); and an image data conversion device (56), which can convert the image signal into data to facilitate the interpretation of the fluorescence intensity of each analysis sample point. When analyzing the biochip by using the imaging biochip of the present invention, the biochip is first placed on a carrying platform (57). During the analysis, a laser light source (50) emits a light beam, and the light beam passes through a collimating lens (5 丨) to form a large area of parallel light, which passes through the biochip (5 2), so that the biochip

1226437 五 、發明説明(5) (52) 上的螢光物質被激發出螢光。此光訊號通過聚焦 (53) ,並以濾光片(54)濾除干擾光波後,由CCD相 將螢光訊號操取為影像,此影像訊號傳輸至影像數 ) 裝置(56),而將影像訊號轉為數據。為了使數據的 析更方便,此影像數據轉換裝置(5 6 )可為一電腦,此二 (56)可以同時包含控制生物晶片承載平台(57)移動的甸 式,使此顯像式生物晶片儀(5 )更容易操作。 王1226437 V. Description of the invention (5) (52) The fluorescent substance is excited to emit fluorescence. After the optical signal is focused (53) and the interference light wave is filtered by a filter (54), the CCD phase processes the fluorescent signal as an image, and this image signal is transmitted to the image number) device (56), and the The image signal is converted into data. In order to make the analysis of the data more convenient, the image data conversion device (56) can be a computer, and the two (56) can also include a Dian type that controls the movement of the biochip carrying platform (57), so that the imaging type biochip The instrument (5) is easier to operate. king

綜合上述說明及實施例,本發明之顯像式生 利2準直透鏡使雷射光源產生大面積的雷射光激發光源, 使得各樣品點同時接受高效能的激發光源。此外7利/用CCD 相機大面積而快速的擷取生物晶片的螢光影像再進行分 析’可以大幅降低分析時間。In summary of the above descriptions and embodiments, the imaging type 2 collimating lens of the present invention enables the laser light source to generate a large area of laser light excitation light source, so that each sample point simultaneously receives a high-efficiency excitation light source. In addition, the use of a CCD camera to quickly and accurately capture the fluorescence image of a biochip and then analyze it can greatly reduce the analysis time.

1226437 圖式簡單說明 第一圖為習知DNA晶片測定之示意圖。 第二圖為習知生物晶片儀之示意圖。 第三圖為本發明顯像式生物晶片儀之示意圖。 元件符號說明 1 DNA晶片 1 4 習知的生物晶片 4 1聚焦透鏡 42 44晶片 45 47濾波片 48 5 本發明之顯像式 51準直透鏡 52 54濾光片 55 57承載平台 DNA探針 3 儀 40 分光鏡 43 螢光 46 光電倍增管 49 生物晶片儀 50 生物晶片 53 CCD相機 56 目標DNA 雷射光源 聚焦透鏡 聚焦透鏡 電腦 光源 聚焦透鏡 影像數據轉換裝置1226437 Brief description of the diagram The first diagram is a schematic diagram of the conventional DNA wafer measurement. The second figure is a schematic diagram of a conventional biochip instrument. The third figure is a schematic diagram of an imaging biochip of the present invention. Description of component symbols 1 DNA wafer 1 4 Conventional biological wafer 4 1 Focusing lens 42 44 wafer 45 47 filter 48 5 imaging 51 collimator lens 52 54 filter 55 57 bearing platform DNA probe 3 instrument of the present invention 40 Beamsplitter 43 Fluorescence 46 Photomultiplier tube 49 Biochip 50 Biochip 53 CCD camera 56 Target DNA Laser light source focusing lens focusing lens Computer light source focusing lens image data conversion device

第11頁Page 11

Claims (1)

1226437 六、申請專利範圍 1. 一種顯像式生物晶片儀,其至少包含: 一光源,其係用以發出光束; 一準直透鏡,其係使光源所發出之光束形成大面積的平 行光,該平行光通過生物晶片,使生物晶片上之螢光物 質被激發出螢光; 一聚焦透鏡,其係用以使該螢光聚焦; 一濾光片;其係用以濾除干擾光波;以及 一 CCD相機,其係用以將該螢光訊號擷取為影像。 2. 如申請專利範圍第1項所述之顯像式生物晶片儀,該顯像 式生物晶片儀進一步包含一影像數據轉換裝置,此裝置 可將CCD相機所擷取的影像訊號轉為數據。 3. 如申請專利範圍第2項所述之顯像式生物晶片儀,該顯像 式生物晶片儀進一步包含一承載平台,用以承載該生物 晶片,該承載平台可作X轴向移動。 4. 如申請專利範圍第3項所述之顯像式生物晶片儀,該顯像 式生物晶片儀進一步包含一電腦,該電腦至少包含一組 控制該承載平台移動方向的控制參數。 5. 如申請專利範圍第:4項所述之顯像式生物晶片儀,其中該 電腦可作為影像數據轉換裝置,其係至少包含一組可將 該CCD相機所擷取的影像訊號轉為數據的參數。1226437 VI. Application Patent Scope 1. An imaging biochip, which includes at least: a light source for emitting a light beam; a collimating lens for forming a large area of parallel light from the light beam emitted by the light source, The parallel light passes through the biochip, so that the fluorescent substance on the biochip is excited to emit fluorescence; a focusing lens for focusing the fluorescence; a filter; it is used for filtering out interference light waves; and A CCD camera is used to capture the fluorescent signal as an image. 2. The imaging biochip apparatus described in item 1 of the scope of patent application, the imaging biochip apparatus further includes an image data conversion device, which can convert the image signal captured by the CCD camera into data. 3. The imaging biochip apparatus described in item 2 of the scope of patent application, the imaging biochip apparatus further comprises a carrying platform for carrying the biochip, and the carrying platform can move in the X-axis direction. 4. The imaging biochip apparatus described in item 3 of the scope of patent application, the imaging biochip apparatus further includes a computer, the computer including at least a set of control parameters that control the moving direction of the bearing platform. 5. The imaging biochip device as described in the scope of patent application: Item 4, wherein the computer can be used as an image data conversion device, which includes at least one group that can convert the image signals captured by the CCD camera into data Parameters.
TW92123648A 2003-08-27 2003-08-27 Image display type biochip instrument TWI226437B (en)

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