High-Speed Neonatal Screening by Photoionization MS/MS

描述(由申请人提供)：这个小型企业创新研究第一阶段项目将测试一种新的高通量质谱学方法在新生儿遗传疾病筛查中的可行性。质谱学的下一个主要应用领域可能是临床诊断学。在过去的几年里，LC/MS和MS/MS已被证明是一种有效的新生儿疾病筛查方法。一种有希望的方法是基于流动注射分析(FIA)，使用电喷雾电离(ESI)与工作在前驱体或中性损耗MS/MS模式的三重四极杆MS相耦合。通过测量氨基酸和酰肉碱的异常比率，该方法能够在每个样本短短2分钟的时间内筛选出多种疾病，但在分析之前需要大量的样本准备。我们提出了一种方法，可以显著提高分析速度、准确度和每份样品的成本，并且比目前的方法需要更少的样品准备。我们的方法是基于使用低压光电离(LPPI)耦合到四极离子陷阱，飞行时间(QitTof)质谱仪(MS)。其主要优点是(I)LPPI与ESI相比最大限度地减少了离子抑制，(Ii)QitTof与三重四极杆MS相比提高了MS/MS分析的速度，以及(Iii)简化了样品制备要求。

DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project will test the feasibility of a new high-throughput mass spectrometry method for screening genetic disorders in newborns. The next major application area for mass spectrometry is likely to be in clinical diagnostics. In the past few years, LC/MS and MS/MS have been shown to be effective screening methods for a host of neonatal disorders. A promising method is based on flow injection analysis (FIA) using electrospray ionization (ESI) coupled to a triple quadrupole MS operating in precursor or neutral loss MS/MS mode. By measuring abnormal ratios for amino acids and acylcarnitines, this method is capable of screening for multiple disorders in as little time as 2 min per sample, However, significant sample preparation is required before analysis. We propose a method that can significantly improve analysis speed, accuracy, and cost per sample, and which potentially requires less sample preparation than the current methods. Our method is based on the use of low-pressure photoionization (LPPI) coupled to a quadrupole ion trap, time-of-flight (QitTof) mass spectrometer(MS). The principal advantages are (i) minimization of ion suppression by LPPI vs ESI, (ii)increased rate of MS/MS analysis by QitTof vs triple quadrupole MS, and (iii) simplification of the sample preparation requirements.