Nature BME:微针贴片对间质液中蛋白质生物标志物的超灵敏定量研究

2021-02-16 MedSci原创 MedSci原创

间质液(ISF)与其他外周生物流体(如唾液、汗液和眼泪)相比,它是一种特别丰富的可溶性生物分析物来源,包括蛋白质、肽、代谢物和核酸。它还代表感兴趣的特定组织的局部区域生物分子组成。简单而有效的方法能够

间质液(ISF)与其他外周生物流体(如唾液、汗液和眼泪)相比,它是一种特别丰富的可溶性生物分析物来源,包括蛋白质、肽、代谢物和核酸。它还代表感兴趣的特定组织的局部区域生物分子组成。简单而有效的方法能够对ISF进行全面的分析,能导致生物诊断技术的变革性进步,这些技术不仅具有微创性和无痛性,而且非常适合护理点和资源有限的环境。但是提取ISF然后进行体外分析在临床前或临床应用中尚未得到广泛应用,主要是因为(1)提取ISF困难,耗时且需要笨重的仪器,(2)使用当前技术只能提取的少量ISF,这对于全面的蛋白质组学和代谢组学分析是不够的。

带有生物识别元件的功能化微针可以特异性捕获ISF中的目标生物标记物,随后可以进行体外分析,提供了一种很有前景的技术。然而,ISF中蛋白质生物标记物的生理浓度通常比血液中的低。此外,由于密集的组织环境,目标生物分子向传感器表面(即微针表面)的扩散减慢,进一步降低分析物捕获的概率和相应于分析物的后续信号强度。这些挑战加剧了间质液中蛋白质生物标志物检测的难度。本文展示了在ISF中,超灵敏和定量测量的靶蛋白生物标志物的活体取样和分析。

figure1

为了提高基于微针的免疫分析的灵敏度,使用了一种超亮的荧光纳米标记,称为等离子荧光,与传统荧光团相比,它将各种ISF蛋白生物标记物的检测限提高了近800倍,并显著缩短了采样时间。此外,通过利用微针的双层设计,能够在微针贴片上复制传统的免疫分析程序,包括基于“标准微贴片”的校准曲线。利用一系列小鼠模型,证明了微针贴片可以用于超灵敏和定量监测各种蛋白质生物标志物。

figure3

首先,通过监测皮肤ISF中的可卡因特异性抗体来探讨可卡因疫苗的有效性。第二,证明了内毒素介导休克诱导后小鼠炎症生物标志物水平的敏感检测和纵向监测。最后,验证了微针贴片在颅骨骨膜基质细胞蛋白骨膜蛋白(POSTN)检测和定量中的应用,这是一个使用野生型(WT)和骨膜蛋白敲除(PostnKO)小鼠进行检测的位点。微创微针贴片避免了在短时间内破坏靶组织和重复抽血的需要,这可能导致患者依从性差或在临床前环境下实验小鼠的潜在死亡。这种超灵敏的生物检测技术可以使微针贴片广泛用于生物标记物的捕获和分析。

生物检测方法可能广泛适用于快速及时诊断和个体化治疗是有效干预措施的其他疾病。例如,当病人在经历胸痛后被转移到急诊室时,可以通过在救护车上应用微针补片(特定于心肌肌钙蛋白)来加速心肌梗死的诊断。此外,这项技术还可以通过微针贴片的自我给药在家取样和集中检测生物标志物水平,最终能够及时监测治疗,如某些抗生素治疗、化疗或检查点抑制剂免疫治疗。因此,这种传感技术可以潜在地应用于护理点和资源有限的环境中,以更方便患者的方式促进快速疾病诊断和有效的治疗干预。

Wang, Z., Luan, J., Seth, A. et al. Microneedle patch for the ultrasensitive quantification of protein biomarkers in interstitial fluidNat Biomed Eng 5, 64–76 (2021). https://doi.org/10.1038/s41551-020-00672-y

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    2021-04-22 liye789132251
  4. [GetPortalCommentsPageByObjectIdResponse(id=2016057, encodeId=37b0201605efd, content=<a href='/topic/show?id=d4a95082e62' target=_blank style='color:#2F92EE;'>#微针贴片#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50827, encryptionId=d4a95082e62, topicName=微针贴片)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45b2276, createdName=839640778, createdTime=Tue Dec 14 02:29:23 CST 2021, time=2021-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841642, encodeId=a3131841642de, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Sun Mar 14 20:29:23 CST 2021, time=2021-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884982, encodeId=f18f18849828d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Apr 22 13:29:23 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1765854, encodeId=91cf1e658546d, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Thu Jul 15 18:29:23 CST 2021, time=2021-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1764169, encodeId=7ec81e64169c4, content=<a href='/topic/show?id=844492480bb' target=_blank style='color:#2F92EE;'>#贴片#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92480, encryptionId=844492480bb, topicName=贴片)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56f237637156, createdName=12498b37m84暂无昵称, createdTime=Tue Nov 23 17:29:23 CST 2021, time=2021-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297130, encodeId=a313129e13043, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Feb 17 15:29:23 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1561006, encodeId=a6ad1561006c1, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Feb 17 15:29:23 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1567015, encodeId=1c3d156e015b1, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Feb 17 15:29:23 CST 2021, time=2021-02-17, status=1, ipAttribution=)]
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