Sample inlets miniaturization

While ESI and MALDI are the most commonly used ionization techniques for the MS analysis of biological samples, many other ionization mechanisms do exist and some of them were already implemented on microfluidic devices. APCI and various laser desorption ionization sources were pursued. A miniaturized APCI nebulizer chip, fabricated from silicon and Pyrex glass wafers, was designed to accommodate sample inlet capillaries, a stopper, a vaporizer channel, and a nozzle. The nebulizer chip was used to interface capillary LC to MS, but could be integrated within CE separation chips as well. 

Miniature handheld detection system Battery powered, vapor sampling Estimated operating time -4 hours Results in 1-3 seconds Version 1 —lab prototype Version 2—planned improvements Optimize performance Data acquisition and data analysis software Embedded processor and LCD New inlet configuration... 

A miniaturized mass spectrometer with APCI was built [21], The analyzer was a monopole with 54 mm rod length and 2 mm radius. A two-stage differentially pumping system and sampling nozzle of 80p,m enabled an inlet gas flow rate of 1 ml/s. The ion current generated by the corona discharge was 0.01-10 p,A. 

The nano-electrospray (nanoES) source is essentially a miniaturized version of the ES source. This technique allows very small amounts of sample to be ionized efficiently at nanoliters per minute flow rates and it involves loading sample volumes of 1-2 pi into a gold-coated capillary needle, which is introduced to the ion source. Alternatively for on-line nanoLC-MS experiments the end of the nanoLC column serves as the nanospray needle. The nanoES source disperses the liquid analyte entirely by electrostatic means [27] and does not require assistance such as solvent pumps or nebulizing gas. This improves sample desolvation and ionization and sample loading can be made to last 30 minutes or more. Also, the creation of nanodroplets means a high surface area to volume ratio allowing the efficient use of the sample without losses. Additionally, the introduction of the Z-spray ion source on some instruments has enabled an increase in sensitivity. In a Z-spray ion source, the analyte ions follow a Z-shaped trajectory between the inlet tube to the final skimmer which differs from the linear trajectory of a conventional inlet. This allows ions to be diverted from neutral molecules such as solvents and buffers, resulting in enhanced sensitivity. 

Another approach to increase the loadabihty is to enrich the analyte at the capillary inlet by means of an adsorptive phase, as reviewed in detail in Ref. 10. Re-versed-phase materials such as octadecyl-bonded silica have regularly been used in the form of membranes or column materials, thus, in principle, performing miniaturized SPE ( SPE) in-line with CE, allowing injections of 10-15 /uL. More selective sample concentration is obtained when using antibodies or Fab fragments for coating the inner wall of the capillary inlet [3,5]. 

Additionally, miniaturization of the sources also leads to a decrease of the sample flow rate and the use of a lower ionization voltage. Ionization conditions are smoother, and the ionization source can be placed closer to the mass spectrometer inlet. Consequently, not only more ions are formed, but also more ions enter the mass spectrometer for their analysis. 

An example of one of TSA/TSL s R D funded MEMS based project is the Sandia National Laboratories (SNL) MicroHound project. This is based on the SNL Micro Chem Lab on a Chip , illustrated in Figure 1. The original prototype system from SNL was developed for high vapour pressure, chemical weapons (CW) detection, which utilized a MEMS GC separator, with miniature surface acoustic wave (SAW s) based sensors. The system included an inlet, coated pre-concentrators, detectors, and pumps. To make this useful for trace explosives detection, the addition of an alternate front-end sample collection/macro-preconcentrator and MEMS based coated-preconcentrator is necessary, along with the option to utilize or exclude the MEMS GC separator followed by detection by either, or both, SAW s and miniaturized IMS detectors. 

Miniature cylindrical ion trap array An approach to the rapid screening of large numbers of samples in the areas of proteomics, industrial process monitoring, and metabolomics is to use a multiplexed inlet system with a multiplexed mass spectrometer having an equal number of parallel sample channels. To this end, a high-throughput mini-CIT array mass spectrometer has been developed and tested. 

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