TUNABLE IR LASER MASS SPECTROMETER FOR DNA ANALYSIS

基质辅助激光解吸电离质谱（MALDI-MS） 具有独特的多核苷酸分析潜力， 其他软电离方法，由于其能够引入大量离子， 将寡核苷酸分子转化为气相，样品降解最小。 我们已经提出了一种可调谐红外激光器来扩展这种能力， 探索各种解吸矩阵和协议，以克服 低电离效率和亚稳态衰变， 在第一阶段，我们已经建立了一个新的，可调谐的，红外 光源由一个光参量振荡器（OPO）组成，该振荡器由 可调谐Cr：LiSAF激光器，并获得高分辨率Δ m小于 15在mu/z=5735，S/N大于150）DNA的IR-MALDI质谱， 蛋白质和缩氨酸。在这次成功的 在可行性研究中，我们将在第二阶段建造一个原型紧凑型IR- MALDIMS仪器具有分析大生物分子的独特潜力 在高吞吐量下。该仪器将集成延迟离子 用二极管泵浦的Cr：LiSAF/0 P0激光器的提取T0 F-MS， 2.7到3.4 μ，可以在宽范围内激发O-H，C-H和N-H键。 矩阵 利用该仪器进行DNA分析及MALDI优化 技术将被执行。这项工作将有助于开发新的功能， MALDI-MS对生物医学分析具有根本性的影响。 拟定商业应用： 许多医学和临床应用，如DNA和RNA分析，PCR 片段、蛋白质和肽。DNA诊断 应用将使紧凑，成本有效， MALDI-MS系统用于医疗保健、医学、农业和 环境监测领域。

Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) has a unique potential for polynucleotide analysis beyond the limits of other soft ionization methods, because of its ability to introduce large oligonucleotide molecules into gas phase, with minimum sample degradation. We have proposed a tunable infrared laser to expand this capability, by exploring a variety of desorption matrices and protocols for overcoming low ionization efficiency and metastable decay encountered with conventional UV-MALDI-MS. In Phase I, we have built a novel, tunable, IR source consisting of an optical parametric oscillator (OPO) pumped by a tunable Cr:LiSAF laser, and obtained high resolution delta m is less than 15 at mu/z=5735, S/N is greater than l50) IR-MALDI mass spectra of DNA, protein and peptides with this laser. Following this successful feasibility study, we will build, in Phase II, a prototype compact IR- MALDIMS instrument having unique potential to analyze large biomolecules at high throughput. This instrument will integrate a Delayed-ion Extraction T0F-MS with diode-pumped Cr:LiSAF/0P0 laser widely tunable from 2.7 to 3.4 mu, which can excite O-H, C-H and N-H bonds in wide range of matrices. Using this instrument DNA analysis and optimization of MALDI techniques will be performed. This work will help develop new features of MALDI-MS with fundamental impact on biomedical analysis. PROPOSED COMMERCIAL APPLICATION: Many medical and clinical applications such as, analysis of DNA & RNA, PCR fragments, proteins and peptides, are envisaged. The DNA diagnostics application will enable commercialization of compact, cost effective, MALDI-MS systems for use in health-care, medicine, agriculture, and environmental monitoring fields.