Controversy over the role of antioxidants in cancer has persisted for decades. Here, we demonstrate that synthesis of the antioxidant glutathione (GSH), driven by GCLM, is required for cancer ...initiation. Genetic loss of Gclm prevents a tumor’s ability to drive malignant transformation. Intriguingly, these findings can be replicated using an inhibitor of GSH synthesis, but only if delivered prior to cancer onset, suggesting that at later stages of tumor progression GSH becomes dispensable potentially due to compensation from alternative antioxidant pathways. Remarkably, combined inhibition of GSH and thioredoxin antioxidant pathways leads to a synergistic cancer cell death in vitro and in vivo, demonstrating the importance of these two antioxidants to tumor progression and as potential targets for therapeutic intervention.
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•The GSH antioxidant pathway is required for cancer initiation•After cancer initiation, GSH is dispensable due to alternative antioxidant pathways•The TXN antioxidant pathway is upregulated in tumors•Inhibition of both GSH and TXN pathways causes synergistic cancer cell death
Harris et al. show that the antioxidant glutathione (GSH) is required for cancer initiation but not for established tumors partly due to upregulation of the thioredoxin (TXN) antioxidant pathway in the latter. Consequently, blocking both GSH and TXN pathways synergistically inhibits tumor growth.
We describe a compact luminescent gaseous oxygen (O
2) sensor microsystem based on the direct integration of sensor elements with a polymeric optical filter and placed on a low power complementary ...metal-oxide semiconductor (CMOS) imager integrated circuit (IC). The sensor operates on the measurement of excited-state emission intensity of O
2-sensitive luminophore molecules tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) (Ru(dpp)
3
2+) encapsulated within sol–gel derived xerogel thin films. The polymeric optical filter is made with polydimethylsiloxane (PDMS) that is mixed with a dye (Sudan-II). The PDMS membrane surface is molded to incorporate arrays of trapezoidal microstructures that serve to focus the optical sensor signals on to the imager pixels. The molded PDMS membrane is then attached with the PDMS color filter. The xerogel sensor arrays are contact printed on top of the PDMS trapezoidal lens-like microstructures. The CMOS imager uses a 32
×
32 (1024 elements) array of active pixel sensors and each pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. Correlated double sampling circuit, pixel address, digital control and signal integration circuits are also implemented on-chip. The CMOS imager data is read out as a serial coded signal. The CMOS imager consumes a static power of 320
μW and an average dynamic power of 625
μW when operating at 100
Hz sampling frequency and 1.8
V DC. This CMOS sensor system provides a useful platform for the development of miniaturized optical chemical gas sensors.
In this paper, we review nanoporous materials, with meso/microscale pores, that provide a highly versatile and useful platform for immobilization and encapsulation of recognition elements for optical ...chemical and biological sensors. Specifically, we describe sol-gel process derived xerogels, electrochemical wet and dry-etched porous silicon, and holographically ordered porous polymer gratings (Bragg structures). These materials offer several advantages including low cost, ease of fabrication, high surface to volume ratio, biocompatibility, functionality with various recognition elements, and the ability to modify the material surface/volume properties and porosity. In addition, several optical sensing modalities can be employed using these materials including luminescence emission and lifetime sensing, diffraction, refractive index modulation, colorimetry, ratiometry, and reflection (or transmission). Finally, we review emerging techniques employing these materials that aim toward improving detection efficiency, sensitivity, and selectivity in optical sensors including plasmonics, photonic bandgap structures, and molecular imprinted materials.
A new method for enhancement of luminescence from sol-gel based sensors is demonstrated, utilising the quenching effect and filtering effect of a gold film. Ruthenium ...(4,7-diphenyl-1,10-phenanthroline)3Cl2 is encapsulated in a trimethoxysilane (TEOS) xerogel and spin-coated to an approximate thickness of less than 100nm. Using off axis illumination of the xerogel film, luminescence was collected using a photodiode below the plane of the gold and doped thin film. The gold had the effect of improving all sensor figures of merit via two mechanisms. Firstly, the transmission spectrum of the gold film peaks at 520nm but allows poor transmission of excitation light at 450nm reducing stray light interference in addition to a 550nm cut-on filter. Secondly, and more, importantly relatively insensitive luminophores within approximately 10nm of the gold film are quenched resulting in a significant noise reduction by removal of insensitive residual metal ion-ligand complex luminescence. It is questioned whether an element of radiative-decay-engineering of luminescence is occurring with luminophore emission coupling to the gold film and initiating plasmonic emission from the underside of the film, but no evidence either in terms of solely p-polarisation or increased intensity of luminescence was evidenced. This confirms that the sensor enhancement mechanism is primarily the function of metal quenching as evidenced by reduced background intensity as noise and improved response time to oxygen quenching indicating that only the most sensitive luminophores are available to be dynamically quenched by formation of the ruthenium:oxygen charge transfer complex. This simple sensor geometry improves a basic oxygen sensor luminophore:matrix combination and stands comparison with more complex combinations such as those achieved with fluorinated sol-gel matrices.
We present the design and implementation of a luminescence-based miniaturized multisensor system using pin-printed xerogel materials which act as host media for chemical recognition elements. We ...developed a CMOS imager integrated circuit (IC) to image the luminescence response of the xerogel-based sensor array. The imager IC uses a 26 × 20 (520 elements) array of active pixel sensors and each active pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. The imager includes a correlated double sampling circuit and pixel address/digital control circuit; the image data is read-out as coded serial signal. The sensor system uses a light-emitting diode (LED) to excite the target analyte responsive luminophores doped within discrete xerogel-based sensor elements. As a prototype, we developed a 4 × 4 (16 elements) array of oxygen (O 2 ) sensors. Each group of 4 sensor elements in the array (arranged in a row) is designed to provide a different and specific sensitivity to the target gaseous O 2 concentration. This property of multiple sensitivities is achieved by using a strategic mix of two oxygen sensitive luminophores (Ru(dpp) 3 2+ and Ru(bpy) 3 2+ ) in each pin-printed xerogel sensor element. The CMOS imager consumes an average power of 8 mW operating at 1 kHz sampling frequency driven at 5 V. The developed prototype system demonstrates a low cost and miniaturized luminescence multisensor system.
Oxygen responsive sensor platforms were fabricated by pin printing tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) (Ru(dpp)32+) doped sols onto wavelength tuned reflective Bragg gratings. In ...an epi-luminescence configuration, these Bragg gratings (Gr) were designed to selectively reflect the O2 responsive Ru(dpp)32+ emission toward the detector to enhance the detected signal magnitude. The xerogel based sensors were formed onto (i) glass (XGl), (ii) directly on top of the grating (XGrGl), or (iii) on the glass substrate opposite the grating (XGlGr). The results show that all sensors exhibit linear, statistically equivalent O2 sensitivities, and the XGrGl platform yields up to an 8-fold increase in relative detected analytical signal (RDAS) in comparison to the control (XGl) platform.
We report on the founding member of a unique class of luminescent ionic liquids integrating a photoacidic anion that responds to the presence of both condensed- and gas-phase basicity; the analytical ...response is ratiometric in nature, visible to the naked eye, and offers fascinating prospects in smart photofluids, liquid logic gates, electronic noses, and sensory inks.
As the third-generation rigid macrocycles evolved from progenitor
, cyclic aromatic oligoamides
, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high ...affinity (estimated lower limit of
> 10
M
in CHCl
), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (-49.77 kcal mol
) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of
. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of
results in well-aligned tubular stacks. The persistent tubular assemblies of
, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for
.
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