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QSense耗散型石英晶體微天平在制藥領(lǐng)域中的應(yīng)用

QSense 耗散型石英晶體微天平技術(shù)

耗散型石英晶體微天平（QCM-D）技術(shù)是一項(xiàng)表界面敏感且多功能的分析技術(shù)，主要用于研究薄膜、生物分子相互作用以及其他與表界面相關(guān)的過(guò)程。QCM-D技術(shù)能夠提供關(guān)于分子在固體表面吸附、相互作用和穩(wěn)定性的寶貴見解。

QCM-D技術(shù)可以實(shí)時(shí)監(jiān)控石英晶體芯片的諧振頻率隨時(shí)間的變化。芯片的諧振頻率取決于其質(zhì)量，因此頻率的變化可以揭示與芯片表面耦合的質(zhì)量變化。同時(shí)，還可以實(shí)時(shí)監(jiān)控系統(tǒng)的能量損失（耗散），從而量化芯片上涂層的粘彈性特性。這些頻率和耗散的變化可用于分析分子與芯片表面的相互作用。

QCM-D技術(shù)是由瑞典百歐林科技有限公司和瑞典查爾姆斯理工大學(xué)的科學(xué)家們共同開創(chuàng)的，自1999年原型機(jī)問(wèn)世以來(lái)，QSense耗散型石英晶體微天平產(chǎn)品系列不斷擴(kuò)大。如今，QSense已成為石英晶體微天平儀器的世界leader，廣泛應(yīng)用于制藥、生物技術(shù)、能源、電子、材料、食品、環(huán)境、化學(xué)、礦物加工等領(lǐng)域。數(shù)千篇文獻(xiàn)證明了QSense技術(shù)的可靠性。以下將主要探討QSense耗散型石英晶體微天平技術(shù)在藥物相互作用方面的應(yīng)用。

（一）藥物開發(fā)

QSense的納克級(jí)別質(zhì)量靈敏度為藥物發(fā)現(xiàn)和開發(fā)提供了無(wú)限潛力。通過(guò)QSense進(jìn)行的研究活動(dòng)包括：

1.   各種實(shí)驗(yàn)條件下，實(shí)時(shí)精確監(jiān)測(cè)小分子藥物與蛋白質(zhì)、細(xì)胞膜和RNA的相互作用。[1]

2.   蛋白質(zhì)-蛋白質(zhì)相互作用[2]

3.   小分子與RNA相互作用時(shí)，RNA的結(jié)構(gòu)變化[3]

（二）藥物遞送

 QSense已被證明是一種成本效益高、時(shí)間效率高的技術(shù)，特別適用于表征脂質(zhì)納米顆粒（LNP）及其藥物遞送特性方面。大量文獻(xiàn)證明QSense可以用于：

1.   分析血清蛋白與脂質(zhì)納米顆粒（LNP）的結(jié)合親和力[4]

2.   生物分子（如siRNA和mRNA）在LNP上的結(jié)合與釋放[5]

3.   將LNP遞送到目標(biāo)器官[6]

4.   在無(wú)細(xì)胞環(huán)境中篩選血清蛋白與LNPs的結(jié)合親和力[7]

5.   分析LNPs的表面修飾[8]

6.   脂質(zhì)與生物活性分子（包括藥物、DNA和siRNA）的相互作用[9]

7.   ApoE結(jié)合后對(duì)脂質(zhì)成分分布和整體LNP結(jié)構(gòu)的影響[24]

8.   用于存儲(chǔ)功能化LNP的納米孔陣列[25]

9.   提高LNPs核酸載荷遞送效率的LNP配方[26]

10. 使用cDNA將微泡固定到支持的脂質(zhì)雙層上[27]

11. 穩(wěn)定化立方體的嵌段共聚物與生物模擬脂質(zhì)膜的相互作用[28]

（三）藥物-表面相互作用

QSense在表征藥物配方與表面相互作用方面具有重要意義，涵蓋了生產(chǎn)、純化、儲(chǔ)存和遞送過(guò)程中的多個(gè)方面。特別是評(píng)估生物制藥藥品在整個(gè)生命周期中的表面吸附/解吸附過(guò)程以及吸附層的結(jié)構(gòu)變化。

典型案例包括：

1.   藥物與聚合物、玻璃、金屬和金屬氧化物、硅油等表面的相互作用[10]，[11]，[12]，[13]，[14]，[15]，[16]

2.   輔料在減少藥物-蛋白質(zhì)吸附到表面上的效果[17]

3.   配方條件（濃度、pH值、溫度等）的影響； [18]

4.   界面和界面應(yīng)力在生物制品開發(fā)中的影響[19]

*注：多達(dá) 200 種芯片，可根據(jù)用戶要求定制芯片表面

（四）生物材料與人體組織的相互作用

植入體和生物材料在人體內(nèi)的生物相容性是它們成功發(fā)揮作用的關(guān)鍵。QSense提供了在分子層面對(duì)植入體表面或生物材料與人體血液和組織相互作用的體外分析。

1.   各種眼部護(hù)理配方與黏蛋白/細(xì)胞膜表面的相互作用[20]。

（五）生物傳感器開發(fā)

QSense也被廣泛用于蛋白質(zhì)生物傳感器和即時(shí)檢測(cè)傳感器等類型傳感器的開發(fā)中。

1.   蛋白質(zhì)生物傳感器[21]，[22]

2.   即時(shí)檢測(cè)傳感器(Point-of-care sensors)[23]

QSense Omni 耗散型石英晶體微天平

QSense Omni 是由QCM-D技術(shù)的瑞典百歐林科技有限公司推動(dòng)研發(fā)的new耗散性石英晶體微天平型號(hào)，是QCM-D技術(shù)的集大成者。Omni比市面上任何一款QCM的靈敏度都要高，這使它能夠量化和監(jiān)測(cè)更小的分子、更快的過(guò)程，是研究生物過(guò)程非常理想的工具。QSense有超過(guò)100多種芯片表面材料和涂層可供選擇，支持模擬真實(shí)生物環(huán)境和過(guò)程，以表征蛋白質(zhì)吸附速率、薄膜形成、吸附層剛性、鈣化、細(xì)胞附著等。

QSense Omni 耗散型石英晶體微天平

?   能夠檢測(cè)芯片表面微小至0.24 ng/cm2的變化

?   更快的流體交換（5倍于上代產(chǎn)品），提供更快和更清晰的樣品輸送

?   全系列自動(dòng)化功能，最小化用戶依賴性

?   更簡(jiǎn)化的工作流程和全新直觀的軟件界面，使更廣泛的用戶可以更加容易地使用QCM-D。

參考文獻(xiàn)：

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