QSense耗散型石英晶體微天平在制藥領(lǐng)域中的應(yīng)用

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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年第一臺(tái)原型機(jī)問世以來，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領(lǐng)導(dǎo)者，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)提供了無限潛力。通過QSense進(jìn)行的研究活動(dòng)包括：

各種實(shí)驗(yàn)條件下，實(shí)時(shí)精確監(jiān)測小分子藥物與蛋白質(zhì)、細(xì)胞膜和RNA的相互作用。[1]
蛋白質(zhì)-蛋白質(zhì)相互作用[2]
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：

分析血清蛋白與脂質(zhì)納米顆粒（LNP）的結(jié)合親和力[4]
生物分子（如siRNA和mRNA）在LNP上的結(jié)合與釋放[5]
將LNP遞送到目標(biāo)器官[6]
在無細(xì)胞環(huán)境中篩選血清蛋白與LNPs的結(jié)合親和力[7]
分析LNPs的表面修飾[8]
脂質(zhì)與生物活性分子（包括藥物、DNA和siRNA）的相互作用[9]
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]
用于存儲(chǔ)功能化LNP的納米孔陣列[25]
提高LNPs核酸載荷遞送效率的LNP配方[26]
使用cDNA將微泡固定到支持的脂質(zhì)雙層上[27]
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/解吸附過程以及吸附層的結(jié)構(gòu)變化。

典型案例包括：

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]
輔料在減少藥物-蛋白質(zhì)吸附到表面上的效果[17]
配方條件（濃度、pH值、溫度等）的影響； [18]
界面和界面應(yīng)力在生物制品開發(fā)中的影響[19]

藥物-表面相互作用研究用QCM-D芯片列表
塑料包裝	聚丙烯 (PP) 聚氯乙烯 (PVC) 聚對(duì)苯二甲酸乙二醇酯 (PET) 聚甲基丙烯酸甲酯 (PMMA)	聚乙烯 (PE) 低密度聚乙烯 (LDPE) 高密度聚乙烯 (HDPE) 線性低密度聚乙烯 (LLDPE)
玻璃容器	硼硅酸鹽玻璃	蘇打石灰玻璃
包裝袋	環(huán)烯烴聚合物 (COP)	環(huán)烯烴共聚物 (COC)
過濾材料	聚偏二氟乙烯 (PVDF) 聚四氟乙烯 (PTFE) 聚碳酸酯 (PC)	聚醚砜 (PES) 聚對(duì)苯二甲酸乙二醇酯甘油改性 (PET-G)
預(yù)充填注射器	注射器 PDMS（硅油）
其他相關(guān)材料	聚苯乙烯纖維素不銹鋼L605 SS2343（類似于美國標(biāo)準(zhǔn)316）乙烯-醋酸乙烯共聚物 (EVA)	尼龍聚氨酯醋酸纖維素聚丙烯腈 (PAN) *

*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。

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)檢測傳感器等類型傳感器的開發(fā)中。

蛋白質(zhì)生物傳感器[21]，[22]
即時(shí)檢測傳感器(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)的先驅(qū)者瑞典百歐林科技有限公司推動(dòng)研發(fā)的最新耗散性石英晶體微天平型號(hào)，是QCM-D最新技術(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)測更小的分子、更快的過程，是研究生物過程非常理想的工具。QSense有超過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。

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