Ultrasonic Preparation of Porous Silica-Dye Microspheres: Sensors for Quantification of Urinary Trimethylamine N-Oxide

Abstract

Trimethylamine N-oxide (TMAO), the N-oxide metabolite of trimethylamine (TMA), is a key index in the determination of a wide variety of human cardiac or kidney diseases. A colorimetric sensor array comprising ultrasonically prepared silica-dye microspheres was developed for rapid, portable, and sensitive detection of urinary TMAO. To prepare the sensor array, 13 different organically modified silica (ormosil)-dye composites were synthesized from the hydrolysis/pyrolysis of ultrasonically sprayed organosiloxane precursors under optimized reaction conditions; the resulting products are uniformly sized nanoporous microspheres that are effective colorimetric sensors for various volatile analytes. The effective quantification of aqueous TMAO (which is not volatile) was based on sensing the volatile TMA produced from a simple catalytic reduction of TMAO in situ. RGB color-change patterns from digital images of the sensor array permit precise discrimination among a wide range of TMAO concentrations (10-750 μM) in simulated urine samples; both hierarchical cluster analysis and principal component analysis achieve >99% accuracy in data classification. The calculated limit of detection of urinary TMAO is ∼4 μM, which is substantially below the median level of healthy subjects (∼380 μM). The array of sensors could be simplified to only a couple of strongly responsive elements for the ease of field use, and the process could be developed as a point-of-care tool in combination with digital imaging for the early diagnosis of cardiovascular or kidney diseases from the measurement of fasting urinary level of TMAO.

Keywords: colorimetric sensing; point-of-care device; sensor array; silica-dye microspheres; ultrasonic spray pyrolysis; urinary TMAO.