Desorption/ionization on silicon DIOS

There is a special case of LDI worth mentioning, desorption/ionization on silicon (DIOS) [159, 160], in which analyte compounds are deposited on a surface of etched silicon. With this substrate the mass range can be extended to a few kilodaltons, allowing for analysis of, for example, small peptides without the involvement of a matrix. 

W. G. Lewis, Z. Shen, M. G. Finn, and G. Siuzdak. Desorption/Ionization On Silicon (DIOS) Mass Spectrometry Background and Applications. Int. J. Mass Spectrom., 226(2003) 107-116. 

Lewis, W.G., Shen, Z., Finn, M.G., Siudzak, G. Desorption/ionization on silicon (DIOS) mass spectrometry background and applications. Int. ]. Mass Spectrom. 2003, 226, 107-116. 

G. A mass spectrometry plate reader monitoring enzyme activity and inhibition with a desorption/ ionization on silicon (DIOS) platform. ChemBioChem 2004, 5, 921-927. 

Wall, D. B., Finch, J. W., and Cohen, S. A. (2004). Comparison of desorption/ionization on silicon (DIOS) time-of-flight and liquid chromatography/tandem mass spectrometry for assaying enzyme-inhibition reactions. Rapid Commun. Mass Spectrom. 18 1482-1486. 

A continuous improvement has allowed analysis to reach detection limits at the pico-, femto- and attomole levels [72,73], Furthermore, the direct coupling of chromatographic techniques with mass spectrometry has improved these limits to the atto- and zeptomole levels [74,75], A sensitivity record obtained by mass spectrometry has been demonstrated by using modified desorption/ionization on silicon DIOS method to measure concentration of a peptide in solution. This technique has achieved a lower detection limit of 800 yoctomoles, which corresponds to about 480 molecules [76]. 

Matrix-free direct laser desorption ionization of analyte has been studied on different kinds of surfaces without real success because degradation of the sample is usually observed. However, good results were obtained with the method called surface-activated laser desorption ionization (SALDI) [43] which uses graphite as the surface. But the use of porous silicon as a new surface is more promising and has led to the development of a new method called desorption ionization on silicon (DIOS) [44], Unlike the other matrix-free laser desorption ionization methods, DIOS allows ion formation from analyte with little or no degradation. 

Thomas JJ, Shen Z, Crowell JE, Finn MG, Siuzdak G (2001) Desorption/ionization on silicon (DIOS) a diverse mass spectrometry platform for protein characterization. Proc Natl Acad Sci 98 4932-4937... 

Desorption/ionization on silicon. Another matrix-free approach for the analysis of small molecules is to use modified porous silicon surfaces [61]. A separate name, desorption/ionization on silicon (DIOS), has been coined for this technique [62]. In this approach, the sample is dispensed directly onto a modified porous silicon surface (e.g., silylated porous silicon) and laser-desorbed from the surface. The silicon surface is prepared from flat crystalline silicon by galvanostatic etching. 

When discussing matrix-free LDI strategies, we should also mention one more related approach that resonated in the specialist literature over the past two decades. In desorption/ ionization on silicon (DIOS), a nanostructured silicon chip is utilized as the SALDI-assisting material [81]. After depositing sample solution on such a chip, the sample is ready for LDI-MS analysis. Furthermore, DIOS chips are compatible with microfluidic and microreactor systems [92, 93]. Thus, DIOS-MS has occasionally been implemented in TRMS-related measurements (see also Chapters 7 and 13). 

Figure 3.11 summarizes such key experimental points. As a first point, we have to choose the appropriate ionization method for the detection of small metabolites, we have alternative choices other than MALDI, such as secondary ion mass spectrometry (SIMS) [15], nanostructure-initiator mass spectrometry (NIMS) [20,21], desorption/ionization on silicon (DIOS) [22], nanoparticle-assisted laser desorptiopn/ ionization (nano-PALDI) [23], and even laser desorption/ionization (LDI) [24,25]. We consider that MALDI is stiU the most versatile method, particularly due to the soft ionization capability of intact analyte. However, other methods each have unique advantages for example, SIMS and nano-PALDI have achieved higher spatial resolution than conventional MALDI-IMS, and above aU, these mentioned alternative methods are all matrix-free methods, and thus can exclude the interruption of the matrix cluster ion. Next, if MALDI is chosen, experimenters should choose a suitable matrix compound, solvent composition, and further matrix application method for their target analyte. All these factors are critical to obtain sufficient sensitivity because they affect efficiency of analyte extraction, condition of cocrystallization, and, above all, analyte-ionization efficiency. In addition, based on the charge state of the analyte molecule, suitable MS polarity (i.e., positive/ negative ion detection mode) should be used in MS measurement. Below, we shall describe the key experimental points for MALDI-IMS applications of representative metabolites. 

DESORPTION/IONIZATION ON SILICON (DIOS) AND OTHER MATRIX-FREE APPROACHES... 

Cassie Baxter mode 2 Desorption/ionization on silicon, (DIOS) 4 Fluorescence quenching assay 6 Immunocapture and MALDI (iMALDI MS) 5... 

Law KP (2010) Laser desorption/ionization mass spectrometry on nanostructured semiconductor substrates DIOS (TM) and QuickMass (TM). Int J Mass Spectrom 290 72-84 Law KP, Larkin JR (2011) Recent advances in SALDI-MS techniques and their chemical and bioanalytical applications. Anal Bioanal Chem 399 2597-2622 Lewis WG, Shen Z, Finn MG, Siuzdak G (2003) Desorption/ionization on silicon (DIOS) mass spectrometry background and applications. Int J Mass Spectrom 226 107-116 Li Q, Alonso R, Renner SA, Winefordner JD, Powell DH (2005) Desorption/ionization on porous silicon mass spectrometry studies on pentose-borate complexes. Anal Chem 77 4503-4508 Lin Z, Zhang S, Zhao M, Yang C, Chen D, Zhang X (2008) Rapid screening of clenbuterol in urine samples by desorption electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 22 1882-1888... 

Four of the most commonly used desorption/ionization methods for MSI are secondary ion mass spectrometry (SIMS), desorption electrospray ionization (DESI), matrix-assisted laser desorption/ionization (MALDI), and laser ablation (LA) with post-ionization. Other desorption/ionization approaches such as laser desorption/ionization (LDI) see Chapter 9, (12)), desorption/ionization on silicon (DIOS) (13), electrospray ionization (ESI) (14), and nanostructure-initiator mass spectrometry (NIMS) (15, 16) also have great potential in MSI. Importantly, many mass spectrometers equipped with a MALDI ion source can be used with related ionization processes such as LDI, DIOS, LA, and laser-NIMS. Erequently, a specific ion source arrangement is optimized for a specific mass analyzer for example, MALDI is often interfaced to a time-of-flight (TOF) mass analyzer (described below) although it can also be used with ICR-based instruments. 

Liu, Q., He, L. (2008) Semi-quantitative study of solvent and surfece effects on analyte ionization in desorption ionization on silicon (DIOS) mass spectrometry. J Am Soc Mass Spectrom, 19, 8-13. 

Fig. 15, which shows a characteristic MALDI-TOF spectrum of a two-component protein mixture using sinapinic acid (SA) as a matrix. A broad, tailing peak is observed in the lower mass region of the spectrum (<2000 Da) that is associated with ions from the matrix. This matrix interference is not disturbing in this particular case of protein analysis but could be a disadvantage when smaller molecules are studied. One way to eliminate the matrix interference is the application of the so-called desorption/ionization on silicon (DIOS) technique [36]. 

Matrix-free methods for LD/ionization MS that are espe-dally useful for the analysis of lower molecular mass polymers are desorption/ionization on silicon (DIOS) and surface-assisted laser desorption/ionization (SALDI) MS. A cocrystallization of matrix and analyte is not required and the absence of matrix signals allows the quantitative analysis of low-molecular-mass polymer ions. ... 

---