Silicon micropillar array electrospray chip for drug and biomolecule analysis

Abstract

We have developed a lidless micropillar array electrospray ionization chip (microPESI) combined with mass spectrometry (MS) for analysis of drugs and biomolecules. The microPESI chip, made of silicon, contains a sample introduction spot for a liquid sample, an array of micropillars (diameter, height, and distance between pillars in the range of 15-200, 20-40, and 2-80 microm, respectively), and a sharpened tip for direct electrospray formation. The microchips were fabricated using deep reactive ion etching (DRIE) which results in accurate dimensional control. The chip, providing a reliable open-channel filling structure based on capillary forces and a electrospray emitter tip for ionization, allows an easy operation and reliable, non-clogging liquid transfer. The microPESI chip can be used for a fast analysis using single sampling or for continuous infusion measurements using a syringe pump for sample introduction. The microPESI-MS shows high sensitivity, with limit of detection 30 pmol/L (60 amol or 28 fg) for verapamil measured with tandem mass spectrometry (MS/MS) and using a sample volume of 2.5 microL. The system shows also good quantitative linearity (r2 > 0.99) with linear dynamic range of at least six orders of magnitude and good ion current stability (standard deviation <5%) in 1-h continuous flow measurement. The microPESI-MS is shown to be a very potential method for direct analysis of drugs and biomolecules.

Electrospray Ionization on Solid Substrates

“…8) Other studies introduced the use of polymer microchips for ESI in order to analyze trace amount of analytes. 43,44) e application of other materials, such as polyester, polyethylene, bamboo, fabrics and sponge, as sampling solid substrates for ESI was also demonstrated in recent studies by Wong et al 45) and by our group. 10) in layer chromatography (TLC) plate in layer chromatography (TLC) is a classical technique for separation of mixtures, yet identi cation of an unknown on a TLC plate is not an easy task.…”

Microchip technology in mass spectrometry

“…At best, a potential difference of only 1 kV sufficed to initiate the electrospray (Schultz et al, 2000;Arscott, Le Gac, & Rolando, 2005;Legrand et al, 2007). Silicon-based emitters were also arrayed (Dethy et al, 2003;Deng et al, 2006;Kim et al, 2007) or integrated with a silicon micropillar pattern (Nissilä et al, 2007;Mery et al, 2008). In another approach, an ultrasonically activated electrospray array fabricated of silicon did not contain any protruding nozzles but rather a flat perforated plate on top side and a plate with horn-like nozzles on the underside (Aderogba et al, 2005).…”

“…The tip dimensions were in the range of 1-3 mm, and a particle filter of similar size was implemented on the same chip. Later, sharpfeatured silicon emitters were realized with both in-plane (Arscott, Le Gac, & Rolando, 2005;Kim et al, 2007;Legrand et al, 2007;Nissilä et al, 2007) and out-of-plane (Schultz et al, 2000;Sjödahl et al, 2003;Deng et al, 2006) orientation (Figs. 6 and 7).…”

“…500 mm. Micronozzle density in an array is not usually limited by lithographic patterning or front side etching FIGURE 6. a: Lidless silicon emitters (in-plane) with a micropillar pattern and microfabricated three-dimensional electrospray tip (Nissilä et al, 2007). b: Array of enclosed silicon emitters (in-plane) (Kim et al, 2007).…”

“…6 and 7). These included lidless emitters exploiting capillary action for sample delivery (Arscott, Le Gac, & Rolando, 2005;Legrand et al, 2007;Nissilä et al, 2007) and enclosed emitters with orifice diameters of approximately 10 mm (i.d.) to be operated by pressure-driven flow at 80-300 nL/min (Schultz et al, 2000;Sjödahl et al, 2003;Kim et al, 2007).…”