Sensitivity-Enhanced CMOS Phase Luminometry System Using Xerogel-Based Sensors

Abstract

We present the design and implementation of a phase luminometry sensor system with improved and tunable detection sensitivity achieved using a complementary metal-oxide semiconductor (CMOS) integrated circuit. We use sol-gel derived xerogel thin films as an immobilization media to house oxygen (O2) responsive luminescent molecules. The sensor operates on the principal of phase luminometry wherein a sinusoidal modulation signal is used to excite the luminophores encapsulated in the porous xerogel films and the corresponding phase shift of the emission signals is monitored. The phase shift is directly related to excited state lifetimes of the luminophores which in turn are related to the concentration of the target analyte species present in the vicinity of the luminophores. The CMOS IC, which consists of a 16 times 16 high-gain phototransistor array, current-to-voltage converter, amplifier and tunable phase shift detector, consumes an average power of 14 mW with 5-V power supply operating at a 38-kHz modulation frequency. The output of the IC is a dc voltage that corresponds to the detected luminescence phase shift with respect to the excitation signal. As a prototype, we demonstrate an oxygen sensor system by encapsulating the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) within the xerogel matrices. The sensor system showed a fast response on the order of few seconds and we obtained a detection sensitivity of 118 mV per 1% change in O2 concentration. The system demonstrates a novel concept to tune and improve the detection sensitivity for specific concentrations of the target analyte in many biomedical monitoring applications.

Optical Oxygen Sensors for Applications in Microfluidic Cell Culture

“…Frequency-domain methods of lifetime detection require detection mechanisms capable of detecting phase differences, but separation of luminophores with close lifetimes is easier than with time-domain methods [ 46 ]. Phase fluorometry or luminometry was first used with simple point detectors such as photodiodes and photomultiplier tubes (PMTs) [ 74 – 76 ] but has also been expanded to use two-dimensional detectors to obtain two-dimensional images of oxygen distributions [ 77 ]. Phase-based optical oxygen sensing with photodiode detectors has also been successfully integrated into microfluidic channels and bioreactors [ 78 – 80 ] and even multi-chamber microfluidic cell culture analog systems [ 81 ].…”

“…Several fluorescent, ruthenium-based compounds have been applied to optical oxygen sensing. Compounds of ruthenium-tris-4,7-diphenyl-l,l0-phenanthroline ([Ru(dpp) 3 ] 2+ ) [ 13 , 36 , 41 , 46 , 59 , 60 , 63 , 77 , 81 , 85 – 90 ] and ruthenium(II)-tris(l,l0-phenanthroline) ([Ru(phen 3 ] 2+ ) [ 28 , 38 , 47 , 91 ] are commonly-used examples, and they have been modified to be soluble in silicone films for oxygen sensing [ 92 ]. Other ruthenium compounds used in optical oxygen sensors include dichlorotris (1,10-phenanthroline) ruthenium (II) hydrate [ 93 ] and ruthenium tris (2,2′-dipyridyldichloride)hexahydrate [ 50 , 64 , 66 , 71 , 94 , 95 ].…”

“…Ormosils and sol-gels are very promising as encapsulation matrices, showing excellent optical and physical properties and good porosity/permeability to oxygen as well as the ability for the layer properties to be customized to various sensor applications [ 126 , 127 ]. Oxygen sensors using them have been developed [ 46 , 77 , 88 , 131 – 133 ] and used in various applications, including aquatic sediments [ 41 , 87 ].…”

“…Thin-film type sensors are commonly used, and are generally fabricated by either pipetting or spinning solutions of the indicator and encapsulation medium onto a substrate of interest such as glass slides, polymers, or polyester foils. This type of sensor has been quite widely used as un-patterned films [ 28 , 38 , 46 , 47 , 50 , 62 , 63 , 77 , 91 , 130 ]. A similar process has also been used to create patterned layers by pipetting only small areas or performing a pipetting and lift-off process [ 11 , 12 , 54 , 55 , 61 , 78 , 90 , 125 ].…”

Contact CMOS imaging of gaseous oxygen sensor array

“…Subsequent works were related to DNA microarrays [12,13], modeling and simulation [14], and excited-state lifetime measurements [15]. There are previous reports from several groups on the use of discrete CMOS photodetectors for luminescence monitoring in biochemical sensors [16–21]. More recently, our group proposed chemical sensor microarrays by integration sol–gel derived xerogel sensor microarrays with custom-designed CMOS imager ICs [8,22].…”