近日，清華大學(xué)、普渡大學(xué)和復(fù)旦大學(xué)附屬華山醫(yī)院（以下簡稱“華山醫(yī)院”）合作研究在Analytical Chemistry雜志上發(fā)表了一篇名為“Point-of-Care Tissue Analysis Using Miniature Mass Spectrometer”的文章(點(diǎn)擊查看原文），首次將大氣壓原位電離及小型質(zhì)譜儀用于人體組織的臨床檢測（POCT）應(yīng)用開發(fā)，充分展示小型質(zhì)譜系統(tǒng)未來應(yīng)用于醫(yī)療檢測領(lǐng)域的巨大潛力。

      精準(zhǔn)醫(yī)療，依賴于精確分析手段來支持疾病診斷并指導(dǎo)治療。質(zhì)譜是化學(xué)分析的“金標(biāo)準(zhǔn)”，但由于儀器體積龐大，樣品前處理繁瑣，操作復(fù)雜等原因，一直停留于實(shí)驗(yàn)室分析，無法走入門診或手術(shù)室實(shí)現(xiàn)臨床快檢；而新型原位電離方式與可用于現(xiàn)場檢測的小型質(zhì)譜系統(tǒng)相配合，則為質(zhì)譜進(jìn)入POCT打開突破口。

      清華大學(xué)歐陽證、瑕瑜教授與普渡大學(xué)R. Graham Cooks教授長期合作，致力于小型質(zhì)譜系統(tǒng)、原位采樣電離及脂質(zhì)分析方法的開發(fā)，此次與華山醫(yī)院副院長毛穎教授及神經(jīng)外科花瑋教授合作，使用小型質(zhì)譜系統(tǒng)對(duì)神經(jīng)膠質(zhì)瘤成功地進(jìn)行了精準(zhǔn)分析檢測。神經(jīng)膠質(zhì)瘤發(fā)病率高，惡性率高，手術(shù)治療既要盡可能去除腫瘤，又要減少對(duì)大腦功能的損傷。使用原位采樣離子化小型質(zhì)譜分析系統(tǒng)，可快速實(shí)時(shí)檢測組織活檢樣品中的惡性神經(jīng)膠質(zhì)瘤代謝標(biāo)志物—2-羥基戊二酸（2-HG），提供精準(zhǔn)分子信息，輔助外科醫(yī)師制定手術(shù)方案。

      組織中的脂質(zhì)分析對(duì)尋找疾病標(biāo)記物和臨床檢測也有著重要意義，Nature Methods曾專文討論（查看文章）并報(bào)導(dǎo)清華團(tuán)隊(duì)在脂質(zhì)結(jié)構(gòu)解析（查看文章）及小型質(zhì)譜應(yīng)用方面的工作。在本文中，研究團(tuán)隊(duì)使用小型質(zhì)譜，準(zhǔn)確、快速的分析出大鼠腦、腎和肝組織樣本中的脂類物質(zhì)，并引入光化學(xué)反應(yīng)實(shí)現(xiàn)了不飽和脂質(zhì)異構(gòu)體的快速識(shí)別，區(qū)分小鼠正常乳腺組織和癌組織，作為潛在的癌癥診斷的臨床新方法。

【文章摘要】：
The combination of direct sampling ionization and miniature mass spectrometer presents a promising technical pathway of point-of-care (POC) analysis in clinical applications. In this work, a miniature mass spectrometry system was used for analysis of tissue samples. Direct tissue sampling coupled with extraction spray ionization was used with a homebuilt miniature mass spectrometer, Mini 12. Lipid species in tissue samples were well profiled in rat brain, kidney and liver in a couple of minutes. By incorporating a photochemical (Paternò–Büchi, PB) reaction, fast identification of lipid C=C location was realized. Relative quantitation of the lipid C=C isomer was performed by calculating the intensity ratio C=C diagnostic product ions, by which FA 18:1 (Δ9)/FA 18:1 (Δ11) was found to change significantly in mouse cancerous breast tissue samples. Accumulation of 2-hydroxylglutarate (2-HG) in human glioma samples, not in normal brains, can also be easily identified for rapid diagnosis.