High-Speed Neonatal Screening by Photoionization MS/MS

描述（由申请人提供）：这个小企业创新研究第一阶段项目将测试一种新的高通量质谱法筛查新生儿遗传疾病的可行性。质谱法的下一个主要应用领域可能是临床诊断。在过去的几年中，LC/MS和MS/MS已被证明是有效的筛查新生儿疾病的方法。一种很有前途的方法是基于流动注射分析（FIA），使用电喷雾电离（ESI）耦合三重四极杆质谱，在前驱体或中性损失的质谱/质谱模式下工作。通过测量氨基酸和酰基肉碱的异常比率，该方法能够在每个样品2分钟的时间内筛选多种疾病，然而，在分析之前需要进行大量的样品制备。我们提出了一种可以显著提高分析速度、准确性和每个样品成本的方法，并且可能比现有方法需要更少的样品制备。我们的方法是基于使用低压光电离（LPPI）耦合到一个四极离子阱，飞行时间（QitTof）质谱仪（MS）。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与三重四极杆质谱相比提高了MS/MS分析率，（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.