TW201018905A - Optically-induced microparticle sorting device and method - Google Patents
Optically-induced microparticle sorting device and method Download PDFInfo
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201018905 九、發明說明: 【發明所屬之技術領域】 本發明是有關於一種光驅動(optically-induced)微粒 子分選(sorting)裝置及方法,且特別是有關於一種利用光 介電泳力(dielectrophoretic force)來分離微米粒子之光驅 動微粒子分選裝置及方法。 【先前技術】 • 在生醫檢測系統中,往往需要針對檢體當中某種特定 細胞做採樣研究,但是檢體中除了目標物之外還有許多其 它成份,使得目標物的偵測非常不易。為了增加命中機 率’往往需要使用大量的檢體來進行偵測,因而造成檢體 的浪費。因此,將各種不同的細胞加以分類是—項重要的 步驟,分類完成後就可直擊主要的目標物。 ❹子被電場誘-..... 生對微粒子 電極來造成 作。然而, 計非常的麻 傳統上應心《等級之微粒子分離方式包含有利 冰力或邊銷流方式。介電泳力的產生是利用介電粒201018905 IX. Description of the Invention: [Technical Field] The present invention relates to an optically-induced microparticle sorting apparatus and method, and more particularly to a dielectrophoretic force A light-driven microparticle sorting apparatus and method for separating microparticles. [Prior Art] • In the biomedical detection system, it is often necessary to conduct sampling studies on a specific cell in the sample. However, in addition to the target, the sample has many other components, making the detection of the target very difficult. In order to increase the chance of hitting, it is often necessary to use a large number of samples for detection, thus causing waste of the sample. Therefore, classifying different cells is an important step, and after the classification is completed, the main target can be directly hit. The scorpion is induced by the electric field -..... The pair of microparticle electrodes are created. However, it is very important to consider that the “scale particle separation method includes favorable ice force or side sales. Dielectrophoretic force is generated by using dielectric particles
若聚焦微粒子是帶有 另外’利用邊銷流方式來進行 個常見的缺點。第一是樣品容易受 债測物間的鍵結容易被邊銷流衝斷 5 201018905 接和官能機的磁珠或塑膠珠時,當邊銷流帶有污染物或是 流速過大時’將會使偵測物誤接污染物或是無法接上所需 之接和官能機,導致偵測誤判之結果。 【發明内容】 本發明係有關於一種光驅動微粒子分選裝置及方 法,利用光導(photoconductive)材料形成光虛擬電極 (virtual electrode)來對微粒子產生光介電泳力以進行微粒 ❹子之聚焦及分選操作,可避免傳統之目標物誤判問題以及 微型電極之複雜製程,達到更有效率及更準確之微粒子分 選效果。 根據本發明之第一方面,提出一種光驅動微粒子分選 裝置,用以分選具有不同尺寸之微粒子,此裝置包括一光 ^板。光導板包括聚焦區、微粒尺寸偵測區以及微粒分選 區。聚焦區用以將行經聚焦區之微粒子聚焦排成一列。微 魯區用以偵測排成一列之各個微粒子之尺寸。微 匕括一光虛擬開關,用以根據所偵測到之各個微 =::粒=介電泳力一,將至少兩種: 裝置艮it】:第二方面’提出一種光驅動微粒子分選 導板、同尺寸之微粒子。此Μ包含4 極板以, 第二電極板。光導板包括-第-電 光導材質層。光導材質層設置於篦一#· is拉 上,其中光導_姑哲 、第一電極板 先導材質層包括聚錢、微粒尺寸彳貞魏以及微 2010189()5 粒分選區。聚焦區用以將行經聚焦區之微粒子聚焦排成一 列;微粒尺寸偵測區用以偵測排成一列之各微粒子之尺 寸。微粒分選區包括一光虛擬開關用以根據所偵測到之各 微粒子之尺寸,將至少兩種不同尺寸之微粒子分開。導引 板設置於光導板上用以導引微粒子通過聚焦區、微粒尺寸 偵測區以及微粒分選區。第二電極板設置於導引板上,用 以與第一電極板產生一交流電場。光虛擬開關係於交流電 場中對微粒子產生光介電泳力之排斥作用,以將至少兩種 ❿不同尺寸之微粒子分開。 根據本發明之第三方面,提出一種光驅動微粒子分選 方法,用以分選具有不同尺寸之微粒子。此方法包括利用 光介電泳力之排斥作用,將微粒子聚焦排成一列前進;偵 測排成一列之各個微粒子之尺寸;以及根據所偵測到之各 個微粒子之尺寸,將至少兩種不同尺寸之微粒子分開。 根據本發明之第四方面,提出一種光驅動微粒子分選 方法,用以分選具有不同尺寸之微粒子。此方法包括形成 ❹兩條對稱之光虛擬電極,藉由光介電泳力之排斥作用來聚 焦微粒子;摘測微粒子之聚焦狀況;以及根據所價測到之 微粒子之聚焦狀況,調整光虛擬電極之位置以將微粒子 聚焦成一列前進。 為讓本發明之上述内容能更明顯易懂,下文特舉一較 佳實施例,並配合所附圖式,作詳細說明如下: 【實施方式】 201018905 請同時參照第1A圖及第1B圖, 明較佳實施例之一種光驅動微粒子分^ 1不依照本發 圖以及第1A圖中光導板之結構示刀、、置之方塊示意 選裝置1GG係用以分選具有不同$ ^光驅動微粒子分 細胞等,其包括光導板110、導引板Ί寸之微粒子,例如 纖偵測單元140、影像擷取單元〗 電極板130、光 控制單元170,其中光導板11〇、導、曼影單元以及 在實際操作時係為彼此重疊配置, 2G及電極板130 1A圖中係以分開方式顯示。 …、、、了說明方便’在第 d nt :圖所示’光導板U〇由左至右依序包括聚隹 £ 112、微粒尺寸偵測區114以 斤L括聚焦 112具有對稱配置之兩條光虛擬電極^選區广。聚焦區 是沿著微粒子行進方向逐漸縮小。^此之間距例如 擬電極⑴之間時,這些微粒子會受田微=行、經兩條光虛If the focused particles are carried out with the other side, the common disadvantage is to use the side pin flow. The first is that the sample is easily affected by the bond between the bonds and is easily broken by the pin. 5 201018905 When the magnetic beads or plastic beads of the functional machine are connected, when the side pin flow has contaminants or the flow rate is too large, The detection of the substance is mistakenly connected to the contaminant or the connection of the desired function and the functional machine is prevented, resulting in the detection of a false positive result. SUMMARY OF THE INVENTION The present invention relates to a light-driven microparticle sorting apparatus and method for forming a photo-viral electrode by using a photoconductive material to generate a photodielectrophoretic force for focusing and subdividing the microparticles. The selection operation can avoid the traditional target misjudgment problem and the complicated process of the micro electrode, and achieve more efficient and accurate microparticle sorting effect. According to a first aspect of the present invention, there is provided a light-driven fine particle sorting apparatus for sorting fine particles having different sizes, the apparatus comprising a light plate. The light guide plate includes a focus area, a particle size detection area, and a particle sorting area. The focus area is used to focus the particles passing through the focus area in a row. The micro-lu zone is used to detect the size of each particle arranged in a row. A micro-virtual switch is used to select at least two according to the detected micro-::granule=dielectrophoretic force one: device 艮it: second aspect' proposes a light-driven particle sorting guide Plate, particles of the same size. This crucible contains a 4-pole plate and a second electrode plate. The light guide plate includes a layer of a -electro-optical guide material. The light guide material layer is arranged on the 篦一#· is pulled, wherein the light guide _ Guzhe, the first electrode plate, the lead material layer includes the money collecting, the particle size 彳贞Wei and the micro 2010189 () 5 grain sorting area. The focus area is used to focus the particles passing through the focus area in a row; the particle size detection area is used to detect the size of each of the particles arranged in a row. The particle sorting zone includes a light virtual switch for separating at least two different sized particles based on the size of each of the detected microparticles. The guiding plate is disposed on the light guiding plate for guiding the particles to pass through the focusing area, the particle size detecting area and the particle sorting area. The second electrode plate is disposed on the guiding plate to generate an alternating electric field with the first electrode plate. The optical virtual opening is related to the repulsion of the photoelectrophoretic force generated by the microparticles in the alternating current field to separate at least two kinds of microparticles of different sizes. According to a third aspect of the present invention, a light-driven fine particle sorting method for sorting fine particles having different sizes is proposed. The method includes aligning the microparticles into a column by utilizing the repulsive force of the photodielectrophoretic force; detecting the size of each of the microparticles arranged in a row; and, according to the size of each of the detected microparticles, at least two different sizes The microparticles are separated. According to a fourth aspect of the present invention, there is provided a light-driven fine particle sorting method for sorting fine particles having different sizes. The method comprises forming two symmetrical light virtual electrodes, focusing the microparticles by the repulsive force of the photodielectrophoretic force; extracting the focusing state of the microparticles; and adjusting the optical dummy electrode according to the focus state of the microparticles measured by the price Position to focus the particles in a row. In order to make the above description of the present invention more comprehensible, the following description of the preferred embodiment and the accompanying drawings will be described in detail as follows: [Embodiment] 201018905 Please refer to FIG. 1A and FIG. 1B simultaneously. A light-driven fine particle segment of the preferred embodiment is not shown in accordance with the structure of the light guide plate in FIG. 1A and FIG. 1A, and the block-selecting device 1GG is used for sorting different light-driven fine particles. a cell, etc., comprising a light guide plate 110, a microparticle of the guide plate, such as a fiber detecting unit 140, an image capturing unit, an electrode plate 130, and a light control unit 170, wherein the light guiding plate 11 导, guide, and the image unit And in the actual operation, they are arranged to overlap each other, and the 2G and the electrode plates 130 1A are displayed in a separate manner. ..., , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Strip light virtual electrode ^ wide selection. The focus area is gradually reduced along the direction in which the particles travel. ^When the distance between them is, for example, between the pseudo-electrodes (1), these micro-particles will be affected by Tian Wei = line, two light imaginary
成-列前進。而在兩條光虛擬電極ill中間排 …可二包含:Γ?粒子聚焦成-列前進,聚焦區 ln(第1㈣顯示有三組之對稱配虛擬電極 微粒尺寸偵測區m係用以.置=擬電極1U)。 尺寸及數目,乂偵/則排成一列之微粒子之 個微粒子之尺^粒分選區116係'用以根據㈣測到之各 至不同之行$向將至少兩種不同尺寸之微粒子分開導引 板二導係為表面,佈光導材質層之電極板。光導 玉板可以疋塗佈銦錫氧化物(Indium Tin 201018905Into-column advances. In the middle of the two optical virtual electrodes ill... can include: Γ? The particles are focused into a column, and the focus region ln (the first (four) shows three sets of symmetrically arranged virtual electrode particle size detection regions m for use. Pseudoelectrode 1U). Size and number, 乂 / 则 则 则 则 则 则 ^ ^ ^ ^ ^ ^ 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒 粒The plate two guiding system is the surface, and the electrode plate of the light guiding material layer is arranged. Light guide jade plate can be coated with indium tin oxide (Indium Tin 201018905
Oxide; ITO)材質層之玻璃基板。光導板no更可包括塗佈 於ΙΤΟ材質層與光導材質層之間之一銦(molybdenum)材質 層’用以降低塗佈光導材質層之接觸阻抗(contact resistance)及改善其黏著性(adhesion),而光導材質層例如 是一種多晶石夕(amorphous silicon)層。 另外’導引板120 ’例如是SU-8高分子材質,係設置 於光導板110上’且導引板120包括一微粒引道122,用 以導引微粒子依序通過聚焦區112、微粒尺寸摘測區114 參以及微粒分選區116。電極板130,例如是塗佈ιτο的破 璃材質’係設置於導引板120上。電極板13〇包括一注入 孔132,對應設置於微粒引道122之前端上方,用以注入 含有微粒子之流體,例如是含有細胞之檢體。投射光束至 光導板110之光導材質層,料材質層上照光區域的導電 係數隨光電流增加而變大,因此照光區域的部份形成光虛 擬電極111 ’並且光導板110與電極板13〇之間則施加一 交流電。 參 在光虛擬電極110及交流電之作用下,光導板110之 電極板與上方之電極板13G會產生—個不均勻交流電場, 當微粒子通過兩條光虛擬電極11】 ^ ^ ^ 1U之間時,微粒子會感應 形成電偶極並受兩側光介電泳力之排斥作用而聚焦排列 在兩條光虛擬電極1U的中間,達到聚焦微粒子的效果。 光纖摘測單元刚包括利用光纖導光形成之一光發射 器142以及一光接收器144相對地設置於光導W微 粒計數尺寸偵測區114上,用w &、 印以偵蜊通過光發射器142與 9 201018905 光接收器144之間之微粒子尺寸及數目。導引板120更用 以固定及對準光發射器142以及光接收器144。當上述排 成一列之微粒子一個一個依序通過光發射器142與光接收 器144之間時,光發射器142所發出之光束會短暫被通過 之微粒子所遮斷。因此’藉由光接收器144所接收之光訊 號再轉換成電訊號後之電壓強度可得知通過之微粒子尺 寸。 影像擷取單元I50,例如包含電荷耦合元件(charge _pled device ; CCD),用以擷取光導板11〇上光虛擬 極111以及通過光虛擬電極lu之微粒子影像,並將此馬 像回饋至控制單it 17〇。投影單元16㈣以投影光束於= 導板11G上之光導材質層形成光虛擬電極m。控制單-no,、例如是一電腦裝置,係根據影像擷取單元所提 如第2A圖所示,當具有尺寸分別為9.7μιη& 2〇 9μιη φ之微粒子之流體通過光發射器142與光接收器144之間 時,對應尺寸為20.9μιη之較大微粒所測得之電壓值會由 90mv下降為20mv左右,而對應尺寸為97μπι之較小微粒 所測得之電壓值則僅由90mv下降為70mv〜80mv。因此, 根據所測得之電壓強度可判斷出通過光發射器142之微粒 子之尺寸為較大尺寸(20μΐη以上)或較小尺寸(1〇μιη以下)。 〜卞〜所扠彭出之對稱兩條 使得微粒子可以有效聚焦排成— 光虛擬電極111之間距, 列前進。 供之光導板影像來調整投影單元刚所投影出之對Oxide; ITO) The glass substrate of the material layer. The light guide plate no may further include a molybdenum material layer applied between the tantalum material layer and the photoconductive material layer to reduce the contact resistance of the coated photoconductive material layer and improve the adhesion thereof. The photoconductive material layer is, for example, an amorphous silicon layer. In addition, the 'guide plate 120' is, for example, a SU-8 polymer material, which is disposed on the light guide plate 110' and the guide plate 120 includes a particle guide 122 for guiding the particles to pass through the focus region 112 and the particle size. The test area 114 is referenced and the particle sorting area 116. The electrode plate 130 is, for example, a glass material coated with ιτο, provided on the guide plate 120. The electrode plate 13A includes an injection hole 132 correspondingly disposed above the front end of the particle guide 122 for injecting a fluid containing microparticles, such as a sample containing cells. Projecting the light beam to the light guide material layer of the light guide plate 110, the conductivity of the illumination region on the material material layer becomes larger as the photocurrent increases, so that the portion of the illumination region forms the optical dummy electrode 111' and the light guide plate 110 and the electrode plate 13 are An alternating current is applied between them. Under the action of the optical dummy electrode 110 and the alternating current, the electrode plate of the light guiding plate 110 and the upper electrode plate 13G generate an uneven alternating electric field, when the fine particles pass between the two optical dummy electrodes 11 ^ ^ ^ 1 U The microparticles inductively form an electric dipole and are arranged in the middle of the two optical dummy electrodes 1U by the repulsive action of the dielectrophoretic forces on both sides to achieve the effect of focusing the microparticles. The optical fiber pick-up unit includes a light emitter 142 formed by using optical fiber light guides and a light receiver 144 disposed oppositely on the light guide W particle size detecting area 114, and is detected by w & The size and number of particles between the 142 and 9 201018905 light receivers 144. The guide plate 120 is further used to fix and align the light emitter 142 and the light receiver 144. When the above-mentioned arranged particles are sequentially passed between the light emitter 142 and the light receiver 144, the light beam emitted from the light emitter 142 is temporarily blocked by the passing particles. Therefore, the size of the fine particles passed through the optical signal received by the optical receiver 144 after being converted into an electrical signal can be known. The image capturing unit I50 includes, for example, a charge-coupled device (CCD) for capturing the light-mirror 111 of the light guide plate 11 and the micro-image of the photo-virtual electrode lu, and feeding back the image to the control Single it 17 〇. The projection unit 16 (4) forms a light dummy electrode m by projecting a light beam on the light guide material layer on the =11c. The control unit -no, for example, is a computer device, according to the image capturing unit, as shown in FIG. 2A, when a fluid having microparticles having a size of 9.7 μm & 2 〇 9 μιη φ passes through the light emitter 142 and the light. When the receiver 144 is between, the voltage value measured by the larger particle corresponding to the size of 20.9 μm is reduced from 90 mv to about 20 mv, and the voltage measured by the smaller particle corresponding to the size of 97 μm is decreased by only 90 mv. It is 70mv~80mv. Therefore, it can be judged that the size of the fine particles passing through the light emitter 142 is larger (20 μΐη or more) or smaller (1 μ μηη or less) based on the measured voltage intensity. ~ 卞 ~ The symmetrical two of the forks make the particles can be effectively focused into the line - the distance between the light virtual electrodes 111, the column advances. The light guide plate image is used to adjust the pair of projection units just projected
、導弓I 板120以及電極板130之組合結構製備方法流程圖。如第 2B圖所示,於步驟210中,製備上述之光導板11〇:首先, 將洗淨的玻璃基板202濺鍍一層約70nm的ITO材質層204 作為導電層,再於ITO材質層204上濺鍍一層鉬材質層 206 ’用以降低接觸阻抗及改善黏著性,最後利用電漿增 強化學氣相沉積法(plasma-enhanced chemical vapor deposition ;PECVD)沉積約Ιμιη非晶矽(光導材質)層208 於鉬材質層206上。 φ 接著,於步驟220中,於光導板110上塗佈(coating) 一層SU-8高分子層222。然後,於步驟230中,對塗佈 SU-8高分子層222之光導板110進行軟烤(soft baking)程 序。於步驟240,利用光罩242,以紫外線UV對SU-8高 分子層222進行曝光(exposure)程序。接著,於步驟250, 對具有曝光SU-8高分子層222之玻璃基板110進行曝光 後烘烤(post exposure bake)程序。再來,於步驟260中, 對SU-8高分子層222進行顯影(developing)程序,以形成 #上述具有微粒引道之導引板120。然後,於步驟270中, 插入光發射器142及光接收器144於SU-8高分子層222 中。最後,於步驟280中,將上述之電極板130以黏著方 式與具有SU-8高分子層222、光發射器142及光接收器 144之玻璃基板110加以結合。 如第3A圖所示,當兩對稱之光虛擬電極in之最小 間距(例如是130μιη)相對於微粒子尺寸(例如是2〇μΐη)過大 時,由影像擷取單元150所擷取的光導板影像可看出微粒 11 201018905 子並無法聚焦成一列前進、 111之底部以及下方虛擬電極===上方光虛擬電極 可由控制單切〇控制投影單元16^肖前躍進。此時A flow chart of a method for preparing a combined structure of the guide bow I plate 120 and the electrode plate 130. As shown in FIG. 2B, in step 210, the light guide plate 11 is prepared. First, the cleaned glass substrate 202 is sputtered with a layer of ITO material 204 of about 70 nm as a conductive layer, and then on the ITO material layer 204. Sputtering a layer of molybdenum material 206' to reduce contact resistance and improve adhesion, and finally depositing about Ιμιη amorphous germanium (photoconductive material) layer 208 by plasma-enhanced chemical vapor deposition (PECVD). On the molybdenum material layer 206. φ Next, in step 220, a layer of SU-8 polymer layer 222 is coated on the light guiding plate 110. Then, in step 230, the light guiding plate 110 coated with the SU-8 polymer layer 222 is subjected to a soft baking process. At step 240, the SU-8 polymer layer 222 is exposed to ultraviolet light UV using a mask 242. Next, in step 250, the glass substrate 110 having the exposed SU-8 polymer layer 222 is subjected to a post exposure bake procedure. Further, in step 260, the SU-8 polymer layer 222 is subjected to a developing process to form the above-described guide sheet 120 having the particle approach. Then, in step 270, the light emitter 142 and the light receiver 144 are inserted into the SU-8 polymer layer 222. Finally, in step 280, the electrode plate 130 described above is bonded to the glass substrate 110 having the SU-8 polymer layer 222, the light emitter 142, and the light receiver 144 in an adhesive manner. As shown in FIG. 3A, when the minimum pitch (for example, 130 μm) of the two symmetrical light virtual electrodes in is too large with respect to the particle size (for example, 2 〇μΐη), the light guide plate image captured by the image capturing unit 150 is as shown in FIG. It can be seen that the particles 11 201018905 can not be focused into a column of advancement, the bottom of the 111 and the lower virtual electrode ===. The upper optical dummy electrode can be controlled by the control single-cutting unit 16 to jump forward. at this time
之最小間距直到適當大小,例如縮小光虛擬電極1U 所示,由影像擷取 疋5帥1時,如第3B圖 時通過之微粒子已聚 掏取的光導板影像可看出此 u取焦徘成一列前進。 如第1A圖及第1B圖所示 # 117。护制罝-, j 以及至少兩條虛擬通道 微粒二尺 m,以導引/ 160所形成之光虛擬開關 進方向)虛尺寸之微粒子至對應之(不同行 ί 通道117之前端,且控制單元17。係根據 ^微粒子之尺寸,控制投影單元160切換光虛擬電極之 ulS種不同尺寸之微粒子導引至對應之兩條虛擬 如第4Α圖所示’當偵測到微粒子具有較小之尺寸(例 如ΙΟμιη以下)時,控制單元17〇據以切換光虛擬開關出 =位置指向左下方以擋住下方之虛擬通道 117,J1利用光 介電泳力之排斥作用將接近之較小尺寸微粒推到上方之 虛擬通道117。如第4Β圖所示,當偵測到微粒子具有較大 之尺寸(例如20μιη以上)時,控制單元17〇據以切換光虛 擬開關115之位置指向左上方擋住上方之虛擬通道117 , 並利用光介電泳力之排斥作用將接近之較大尺寸微粒推 12 201018905 到下方之虛擬通道117。因此,藉由光虛擬開關115以及 虛擬通道117之設置可有效地將至少兩種不同尺寸之微粒 子導引至不同行進方向之虛擬通道117之中,達到微粒分 選之效果。 此外,如第4C圖所示,光虛擬開關115也可以是包 括平行光導板110且排列成v字型之兩條光虛擬電極,分 別產生不同大小之光介電泳力,用以導引兩種不同尺寸之 微粒子至對應之兩條虛擬通道117。例如:v字型左側之 φ 光虛擬電極產生較小之光介電泳力,而v字型右側之光虛 擬電極產生較大之光介電泳力。較小尺寸之微粒子會先通 過v字型左側之光虛擬電極,接著受到v字型右側之光虛 擬電極之光介電泳排斥力而進入到上方之虛擬通道117。 相對地,較大尺寸之微粒子無法通過v字型左側之光虛擬 電極而直接受到其光介電泳排斥力而進入到下方之虛擬 通道117。 上述具有不同大小光介電泳力之兩條光虛擬電極可 ⑩利用不同色彩,例如是綠色及紅色來產生,或者利用不同 之寬度設計來產生強度差異,或者也可以直接調整色彩的 亮度差(例如是192及255)來形成不同強度之光介電泳力。 上述之光虛擬電極111、光虛擬開關115以及虛擬通 道117可直接在控制單元(電腦裝置)170上利用power point軟體設計來繪製並經由投影單元160投影於光導板 110上而產生,甚至光虛擬開關115之位置切換也可以利 用power point軟體之動畫設計而產生。因此,本實施例利 13 201018905 用光介電泳力來聚焦及分選微粒子可直接透過電腦軟體 來操作及調整,比起傳統之微粒子分離方法,其更具效率 及準痛性,且更可達到直接性的控制。 請參照第5圖,其繪示依照本發明較佳實施例之一種 光驅動微粒子分選方法流程圖。首先,於步驟510,將含 有待分選微粒子之流雜,例如是含有待分選細胞之檢體, 注入微粒引道120之中。此時,含微粒子之流體會由於重 力作用而沿著微粒引道120向前流動。接著,於步驟52〇, •於微粒引道120兩側!光導板110形成對稱之兩條光虛擬 電極111,並搭配上方電極板130及下方光導板11〇之電 極板而形成不均勻電場,藉以對微粒子產生光介電泳力之 排斥作用,使得微粒子可以聚焦排成一列前進。如上所 述,根據影像擷取單元150所獲得之光導板影像可以觀察 微粒子疋否聚焦排成/列則進,並透過控制單元17〇對投 影單元160之控制,可調整光虛擬電極1U之間距以達到 將微粒子聚焦成一列前進之目的。 然後,於步驟530,偵測排成一列之微粒子之尺寸及 數目。例如,利用光纖偵測方式,亦即使用上述光纖偵測 單元140之光發射器142及光接收器144,並根據微粒子 通過光發射器142及光接收器144之間產生之電壓變化可 判斷出所通過之微粒子尺寸。 接著,於步驟540,根據所偵測到之各個微粒子之尺 寸,利用光介電泳力之排斥作用,將至少兩種不同尺寸之 微粒子導引至對應之至少兩種不同行進方向。如第4A圖 201018905 及第4B圖所示’利用一條光虛擬電極切換不同之指向位 置並藉由光介電泳力之排斥作用,以分別導引兩種不同尺 寸(即較小尺寸及較大尺寸)之微粒子至不同之行進方向 (即上方及下方之虛擬通道117)。 或|,如第4C圖所示,利用排列成v字型之兩條光 虛擬電極,分別產生不同大小之光介電泳力,左側之光虛 擬電極產生較小之光介電泳力,而右側之光虛擬電極則產 生較大之光介電泳力,以便將兩種不同尺寸(即較小尺寸及 籲較大尺十)之微粒子分別導引至不同之行進方向(即上方及 下方之虡擬通道117)。 上述聚焦及分選微粒子所使用之光虛擬電極皆可直 接利用電腦軟體設計並經由投影單元在光導板上投影而 產生,由於不需要複雜的黃光製程來製作微型電極,可更 有效率地來進行微粒子分選之操作,並且不會有傳統邊銷 流所造成的誤判情形,有效提高微粒子分選之準確性。 本發明上述較佳實施例所揭露之光驅動微粒子分選 ©裝置及方法具有下列之優點: 一、 利用光虛擬電極所產生之光介電泳力來達到聚焦 微粒子之效果,可避免傳統邊銷流所產生彳貞測誤列問題。 二、 直接利用電腦軟體繪製所需之光虛擬電極,旅町 簡易地由電服軟體來調整光虛擬電極之位置及間斑,因 此,可避免傳統使用固定電極進行微粒聚焦所需之複雜黃 光製程。 三、 本發明僅需改變光虛擬電極的圖形,即玎完成微 15 201018905 粒子之聚焦及分選操作,可達到更有效率、更準確且更直 接之微粒子聚焦及分選之目的。 綜上所述,雖然本發明已以較佳實施例揭露如上,然 其並非用以限定本發明。本發明所屬技術領域中具有通常 知識者,在不脫離本發明之精神和範圍内,當可作各種之 更動與潤飾。因此,本發明之保護範圍當視後附之申請專 利範圍所界定者為準。The minimum spacing is up to the appropriate size, for example, as shown by the reduced light virtual electrode 1U, and when the image is captured by the image, the image of the light guide plate that has been collected by the microparticles as shown in FIG. 3B can be seen as the focus of the u. Going in a row. As shown in Figures 1A and 1B, #117. Guard 罝-, j and at least two virtual channel particles two feet m, to guide / 160 formed light virtual switch into the direction) imaginary size of the particles to the corresponding (different lines ί channel 117 front end, and control unit 17. According to the size of the microparticles, the projection unit 160 controls the ulS of different sizes of the optical dummy electrode to be guided to the corresponding two virtual ones as shown in FIG. 4 'When the microparticles are detected to have a small size ( For example, when ΙΟμηη or below), the control unit 17 switches the light virtual switch out = position to the lower left to block the virtual channel 117 below, and J1 pushes the smaller-sized particles closer to the upper side by the repulsion of the photodielectrophoretic force. The virtual channel 117. As shown in Fig. 4, when it is detected that the microparticles have a large size (for example, 20 μm or more), the control unit 17 switches the position of the optical virtual switch 115 to the upper left to block the virtual channel 117 above. And using the repulsion of the photodielectrophoretic force to push the larger size particles closer to the virtual channel 117 below the 2010-18905. Therefore, by the optical virtual switch 11 5 and the setting of the virtual channel 117 can effectively guide at least two different sized particles into the virtual channel 117 of different traveling directions to achieve the effect of particle sorting. Further, as shown in FIG. 4C, the optical virtual switch 115 may also be two optical dummy electrodes including parallel light guide plates 110 and arranged in a v-shape, respectively generating different sizes of photodielectrophoretic forces for guiding two different sizes of microparticles to corresponding two virtual channels 117 For example, the φ light virtual electrode on the left side of the v-shape produces a small photodielectrophoretic force, while the virtual electrode on the right side of the v-shape produces a large photodielectrophoretic force. Smaller size microparticles will pass through the v-shape first. The virtual electrode on the left side is then subjected to the photodielectrophoresis repulsive force of the virtual electrode on the right side of the v-shape to enter the virtual channel 117 above. In contrast, the larger size of the microparticle cannot pass through the virtual electrode on the left side of the v-shape. Directly subjected to its photodielectrophoresis repulsive force to enter the virtual channel 117 below. The two optical dummy electrodes having different sizes of photodielectrophoretic forces can utilize different colors. For example, green and red are generated, or different width designs are used to generate intensity differences, or the brightness difference of colors (for example, 192 and 255) can be directly adjusted to form light dielectrophoretic forces of different intensities. 111, the optical virtual switch 115 and the virtual channel 117 can be directly drawn on the control unit (computer device) 170 by using the power point software design and generated by projecting on the light guide plate 110 via the projection unit 160, and even the position switching of the optical virtual switch 115 It can also be generated by the animation design of the power point software. Therefore, the present embodiment can be used for focusing and sorting fine particles by optical dielectrophoretic force, which can be directly operated and adjusted through the computer software, compared with the conventional microparticle separation method. More efficient and accurate, and more direct control. Referring to FIG. 5, a flow chart of a method for sorting light-driven particles according to a preferred embodiment of the present invention is shown. First, in step 510, a flow containing the particles to be sorted, for example, a sample containing the cells to be sorted, is injected into the particle guide 120. At this time, the microparticle-containing fluid flows forward along the particle tunnel 120 due to the gravity. Next, in step 52, • on both sides of the particle approach 120! The light guiding plate 110 forms two symmetrical virtual optical electrodes 111, and forms an uneven electric field with the upper electrode plate 130 and the lower optical guiding plate 11 电极 electrode plate, thereby generating a photo-electrophoretic force repulsive effect on the micro-particles, so that the micro-particles can be focused. Line up in a row. As described above, according to the light guide plate image obtained by the image capturing unit 150, the fine particles can be observed to be arranged in a row/column, and the control unit 17 can control the projection unit 160 to adjust the distance between the optical dummy electrodes 1U. In order to achieve the purpose of focusing the particles into a row. Then, in step 530, the size and number of the particles arranged in a row are detected. For example, by using the optical fiber detection method, that is, using the optical transmitter 142 and the optical receiver 144 of the optical fiber detecting unit 140, and determining the voltage change generated by the microparticles passing between the optical transmitter 142 and the optical receiver 144, The size of the particles passed through. Next, in step 540, at least two different sized microparticles are guided to at least two different traveling directions by the repulsion of the photodielectrophoretic force according to the size of each of the detected microparticles. As shown in Fig. 4A, 201018905 and Fig. 4B, 'using a light virtual electrode to switch different pointing positions and repulsion by photodielectrophoresis force to guide two different sizes (i.e., smaller size and larger size) respectively. The particles are in different directions of travel (ie, virtual channels 117 above and below). Or |, as shown in Fig. 4C, using two optical dummy electrodes arranged in a v-shape to generate different sizes of photodielectrophoretic forces, and the left-side optical dummy electrode produces a smaller photodielectrophoretic force, while the right side The optical dummy electrode produces a large photodielectrophoretic force to direct the two different sizes (ie, smaller size and larger size) to different directions of travel (ie, the upper and lower analog channels). 117). The above-mentioned optical dummy electrodes used for focusing and sorting the microparticles can be directly generated by using the computer software design and projected on the light guide plate through the projection unit, and the microelectrode can be produced more efficiently without requiring a complicated yellow light process. The operation of microparticle sorting is carried out, and there is no misjudgment caused by the traditional side pin stream, which effectively improves the accuracy of the microparticle sorting. The light-driven particle sorting apparatus and method disclosed in the above preferred embodiments of the present invention have the following advantages: 1. The effect of focusing the microparticles by using the photodielectrophoretic force generated by the optical dummy electrode can avoid the traditional side pin flow. The resulting misunderstanding problem. Second, directly use the computer software to draw the required light virtual electrode, the travel town simply adjusts the position and the inter-spot of the optical virtual electrode by the electric service software, thus avoiding the complex yellow light required for the conventional use of the fixed electrode for particle focusing. Process. 3. The present invention only needs to change the pattern of the optical dummy electrode, that is, to complete the focusing and sorting operation of the particles, which can achieve more efficient, more accurate and more direct focusing and sorting of the particles. In the above, the present invention has been disclosed in the above preferred embodiments, but it is not intended to limit the present invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, the scope of the invention is defined by the scope of the appended claims.
16 201018905 【圖式簡單說明】 第1A圖係繪示依照本發明較佳實施例之一種光驅動 微粒子分選裝置之方塊示意圖。 第1B圖係繪示第1A圖中光導板之結構示意圖。 第2A圖係繪示第1A圖中光纖偵測單元所測得電壓 強度與時間之關係圖。 第2B圖係繪示第1A圖中光導板、導引板以及電極 板之組合結構製備方法流程圖。 • 第3A圖係繪示第1B圖之光虛擬電極之間距過大所 產生之微粒子移動狀態示意圖。 第3B圖係繪示第1B圖之光虛擬電極之間距適當所 產生排成一列之微粒子狀態示意圖。 第4A圖係繪示第1B圖之光虛擬開關導引較小微粒 子至上方虛擬通道之示意圖。 第4B圖係繪示第1B圖之光虛擬開關導引較大微粒 子至下方虛擬通道之示意圖。 ❹ 第4C圖係繪示第1B圖之光虛擬開關之另一實施例。 第5圖係繪示依照本發明較佳實施例之一種光驅動 微粒子分選方法流程圖。 【主要元件符號說明】 100:光驅動微粒子分選裝置 110 :光導板 111 :光虛擬電極 17 20101890516 201018905 BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a block diagram showing a light-driven microparticle sorting apparatus in accordance with a preferred embodiment of the present invention. FIG. 1B is a schematic view showing the structure of the light guiding plate in FIG. 1A. Fig. 2A is a graph showing the relationship between the measured voltage intensity and the time of the fiber detecting unit in Fig. 1A. Fig. 2B is a flow chart showing the preparation method of the combined structure of the light guiding plate, the guiding plate and the electrode plate in Fig. 1A. • Fig. 3A is a schematic view showing the movement state of the microparticles generated by the excessive distance between the optical virtual electrodes of Fig. 1B. Fig. 3B is a schematic view showing the state of the microparticles arranged in a row between the optical dummy electrodes of Fig. 1B. Figure 4A is a schematic diagram showing the optical virtual switch of Figure 1B directing smaller particles to the upper virtual channel. Figure 4B is a schematic diagram showing the optical virtual switch of Figure 1B directing larger particles to the lower virtual channel. ❹ Figure 4C shows another embodiment of the optical virtual switch of Figure 1B. Figure 5 is a flow chart showing a method of optically driven microparticle sorting in accordance with a preferred embodiment of the present invention. [Description of main component symbols] 100: Light-driven fine particle sorting device 110: Light guide plate 111: Optical dummy electrode 17 201018905
112 : 聚焦區 114 : 微粒尺寸偵測區 115 : 光虛擬開關 116 : 微粒分選區 117 : 虛擬通道 120 : 導引板 122 : 微粒引道 130 : 電極板 132 : 注入孔 140 : 光纖偵測單元 142 : 光發射器 144 : 光接收器 150 : 影像擷取單元 160 : 投影單元 170 : 控制單元 202 : 玻璃基板 204 : ITO材質層 206 : 鉬材質層 208 : 光導材質層 222 : SU-8高分子層 242 : 光罩112 : Focusing area 114 : Particle size detecting area 115 : Light virtual switch 116 : Particle sorting area 117 : Virtual channel 120 : Guide plate 122 : Particle channel 130 : Electrode plate 132 : Injection hole 140 : Fiber detecting unit 142 : Light emitter 144 : Light receiver 150 : Image capturing unit 160 : Projection unit 170 : Control unit 202 : Glass substrate 204 : ITO material layer 206 : Molybdenum material layer 208 : Light guide material layer 222 : SU-8 polymer layer 242 : Photomask
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI487575B (en) * | 2011-06-03 | 2015-06-11 | Kubota Kk | Granular material sorting apparatus |
TWI646196B (en) * | 2017-10-13 | 2019-01-01 | 長庚大學 | Method for screening, separating and purifying rare cells by using dynamic light pattern combined with photodielectrophoresis force |
US10578607B2 (en) | 2017-11-20 | 2020-03-03 | Chang Gung University | Method of screening, isolating, and purifying rare cells |
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2008
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI487575B (en) * | 2011-06-03 | 2015-06-11 | Kubota Kk | Granular material sorting apparatus |
TWI646196B (en) * | 2017-10-13 | 2019-01-01 | 長庚大學 | Method for screening, separating and purifying rare cells by using dynamic light pattern combined with photodielectrophoresis force |
US10578607B2 (en) | 2017-11-20 | 2020-03-03 | Chang Gung University | Method of screening, isolating, and purifying rare cells |
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