In this report, the development of multi-channel Anti-Stokes luminescent Y 2 O 3 nanoparticles for application to in vivo upconversion imaging is detailed.Luminescent upconverting materials have been known for over 50 years. Only recently has interest focused on preparing these compounds on a nanoscale for applications in biotechnology. 1 Current optical imaging and assay technologies primarily are based on the use of organic fluorophores or semiconducting quantum dots. 2 Materials, such as yttrium oxide (Y 2 O 3 ) doped with rare earth elements offer an emerging alternative for use in optical imaging. Erbium and ytterbium containing Y 2 O 3 particles absorb near infrared light at 980 nm and can emit higher energy, shorter wavelength photons in an Anti-Stokes emission process. 3 For bioimaging applications Anti-Stokes luminescence offers key advantages over traditional downconversion emission observed with organic fluorphores and quantum dots. One issue concerning the use of small molecule fluophores is a lack of photostability under prolonged excitation. Unlike organic dyes, upconverting Y 2 O3 nanomaterials show excellent photostability and low toxicity. 4 Quantum dots also have excellent photostability, but there are potential cytotoxicity issues associated with their use in vivo due to their inclusion of highly toxic metals such as cadmium, 5 which is released in the presence of the biological oxidant hypochlorous acid. 6 Tissue autofluorescence is another concern with the use of small molecule fluorophores for in vivo imaging. There are few if any intrinsic biological materials that display upconversion emission, therefore, upconversion emission processes may significantly limit this source of interference.For use of upconverting nanomaterials as in vivo imaging agents, several criteria must be met. These include near infrared excitation and emission, water solubility, biocompatibility, and means for attachment of additional optical reporters or targeting molecules. In the past few years, there have been reports of upconverting nanoparticle preparations that meet some of these criteria. In vivo optical imaging focuses on the use of luminescent reporters that have excitation and emission in the NIR (∼600−1000 nm) where light absorption and scattering from biological tissues is minimized. 8 Excitation and emission in this wavelength range can be achieved by use of Y 2 O 3 nanoparticles co-doped with erbium and ytterbium. 3 These particles may be excited using simple 980 nm diode lasers and show upconversion emission in the green or farred/NIR depending on the concentrations of the dopants. Here we detail the preparation of surface modified upconverting Y 2 O 3 nanoparticles containing erbium and ytterbium, which are suitable for conjugation to additional optical reporters or targeting groups. Importantly these materials can be excited with non-harmful doses of light and have luminescence emission centered at 660 nm. The utility of these particles for in vivo blood pool imaging is demonstrated by visua...

We report a programmable analog bionic ear (cochlear implant) processor in a 1.5-microm BiCMOS technology with a power consumption of 211 microW and 77-dB dynamic range of operation. The 9.58 mm x 9.23 mm processor chip runs on a 2.8 V supply and has a power consumption that is lower than state-of-the-art analog-to-digital (A/D)-then-DSP designs by a factor of 25. It is suitable for use in fully implanted cochlear-implant systems of the future which require decades of operation on a 100-mAh rechargeable battery with a finite number of charge-discharge cycles. It may also be used as an ultra-low-power spectrum-analysis front end in portable speech-recognition systems. The power consumption of the processor includes the 100 microW power consumption of a JFET-buffered electret microphone and an associated on-chip microphone front end. An automatic gain control circuit compresses the 77-dB input dynamic range into a narrower internal dynamic range (IDR) of 57 dB at which each of the 16 spectral channels of the processor operate. The output bits of the processor are scanned and reported off chip in a format suitable for continuous-interleaved-sampling stimulation of electrodes. Power-supply-immune biasing circuits ensure robust operation of the processor in the high-RF-noise environment typical of cochlear implant systems.

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatio-temporal control. Here, we present a novel and generalizable approach, referred to as ‘Chemo-Optical Modulation of Epigenetically-regulated Transcription’ (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may translate into novel therapeutic strategies for diseases where conditional and selective epigenome modulation is required.