煙臺海岸帶所在基于微流控紙芯片的環境與生物分析研發取得系列進展
圖1 (A)應用于環境污染物分析的分子印跡熒光傳感旋轉式微流控紙芯片實物圖與使用操作過程示意圖,(B)該工作以封面論文發表于期刊Analytical Chemistry;(C)應用于腫瘤標志物分析的離心式全血檢測微流控紙芯片示意圖。
圖2 用于生物分析腫瘤標志物的電化學分析微流控紙芯片(A)利用旋轉閥的電化學發光免疫傳感紙芯片的原理、操作示意圖與檢測性能結果圖;(B、C)利用移動閥的分子印跡電化學傳紙芯片的設計組成示意圖與實物圖,及其傳感原理與操作使用過程示意圖。
生物分析與臨床診斷方面,團隊首先研制了旋轉式電化學發光免疫分析紙芯片,利用旋轉閥控制方便操作,完成了紙基多通路的復雜夾心式免疫分析洗滌過程。進一步采用電化學方式,結合移動閥設計,在紙芯片平臺上構建生物分子印跡聚合物,形成了一種基于可移動閥紙裝置原位合成分子印跡聚合物的無抗體生物標志物的電化學分析策略,實現了人體血清中腫瘤標志物癌胚抗原的臨床分析。在利用紙芯片離心全血獲取血清方面也進行了研究,受拉力與繩驅動離心機的啟發,將手動離心方式與旋轉閥紙基免疫分析方法集成于一個紙芯片上,構建了同時具備全血離心功能與免疫分析功能的微流控紙芯片,配合智能手機或便攜式比色分析儀器,在一個紙芯片上實現了從全血離心到免疫分析結果呈現的全過程。研制該芯片用于人體血液中癌胚抗原與甲胎蛋白兩種腫瘤標志物的分析,并在臨床應用實驗和重復性考察上達到較好的效果。(Biosensors & Bioelectronics, 2019, 142 ;Analytical Chemistry, 2017, 89, 5708-5713; Analytica Chimica Acta, 2018, 1007, 33-39 ;Biosensors & Bioelectronics, 2020,接收)。
圖3 紙芯片器件化方面的相關研究成果(A)書頁式移動閥的設計結構之意圖;(B)采用高聚物材料構建紙芯片的方法示意圖與實際應用效果;(C、D)紙基與3D打印芯片混合微流控裝置系統的實物圖、設計原理示意圖以及在癌細胞生物特性研究中的應用效果。
紙芯片器件化方面,該團隊首先研發了靈活控制紙基平臺流體開關的紙基移動閥,并進一步擴展成為書頁式移動閥,更為靈活可拆卸更換,并取得了較好的應用效果。在紙芯片制作方面,利用新型廉價的高聚物材料,作為紙芯片疏水屏障的構建材料,實現了紙芯片上有機溶液的輸送通道的構建,并為紙芯片的制作提供了更廉價的可能,該新型材料制作的紙芯片,在構建紙芯片在環境致病菌的檢測方面得到較好的應用驗證。進一步將紙基與3D打印芯片結合,形成混合微流控裝置系統,利用該微流控系統器件檢測了H2S對癌細胞的影響。發現持續暴露于低濃度H2S可通過誘導細胞凋亡來抑制癌細胞SMMC-7721的生長,此外還發現癌細胞中有兩個氣態分子H2S和NO存在串擾,它們在癌細胞中形成具有生物活性的中間多硫化物。(Analytical Chemistry, 2017, 89, 5708-5713;ACS Sensors , 2018, 3, 1789-1794 ;Sensor and Actuator B-Chemical, 2020, 303, 127213 ;ACS Sensors, 2020, 5, 464-473 ;)。
相關研究得到國家重點研發計劃(Grant No. 2016YFC1400702)、國家自然科學基金(Grant No. 41776110, 21976209),、煙臺市科技發展計劃(2015ZH087)的支持。
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