Cellulose Nanoparticles are a Biodegradable Photoacoustic Contrast Agent for Use in Living Mice.

Molecular imaging with photoacoustic ultrasound is an emerging field that combines the spatial and temporal resolution of ultrasound with the contrast of optical imaging. However, there are few imaging agents that offer both high signal intensity and biodegradation into small molecules. Here we describe a cellulose-based nanoparticle with peak photoacoustic signal at 700 nm and an in vitro limit of detection of 6 pM (0.02 mg/mL). Doses down to 0.35 nM (1.2 mg/mL) were used to image mouse models of ovarian cancer. Most importantly, the nanoparticles were shown to biodegrade in the presence of cellulase both through a glucose assay and electron microscopy

Listening to reporter proteins: how loud does the message need to be?

Optical imaging as non-invasive modality has tremendous research applications in the area of biomedical sciences such as characterization of cancerous cells. However, this imaging modality is limited by depth of light penetration of around 1 mm in living tissues obscuring visualization in vivo. Optoacoustic imaging is a potential solution of this problem based on detection of ultrasound produced by light-absorbing molecules exposed to laser radiation resulting in a tissue contrast. The image contrast relies on absorption of laser emission, however providing ultrasound resolution in living tissues. This study characterized properties of colorectal adenocarcinoma cells expressing Near-infrared Fluorescent proteins (iRFPs) for detection and visualization in Multispectral Optoacoustic Tomography (MSOT) settings in both tissue-mimicking phantoms and mice. We estimated variables affecting MSOT imaging of 3D multicellular tissue spheroids such as size, expression of iRFP in vitro. We tested MSOT for detection of subcutaneously implanted tumours expressing iRFPs in BALB/C nude mice in vivo

Listening to reporter proteins: how loud does the message need to be?

Optical imaging as non-invasive modality has tremendous research applications in the area of biomedical sciences such as characterization of cancerous cells. However, this imaging modality is limited by depth of light penetration of around 1 mm in living tissues obscuring visualization in vivo. Optoacoustic imaging is a potential solution of this problem based on detection of ultrasound produced by light-absorbing molecules exposed to laser radiation resulting in a tissue contrast. The image contrast relies on absorption of laser emission, however providing ultrasound resolution in living tissues. This study characterized properties of colorectal adenocarcinoma cells expressing Near-infrared Fluorescent proteins (iRFPs) for detection and visualization in Multispectral Optoacoustic Tomography (MSOT) settings in both tissue-mimicking phantoms and mice. We estimated variables affecting MSOT imaging of 3D multicellular tissue spheroids such as size, expression of iRFP in vitro. We tested MSOT for detection of subcutaneously implanted tumours expressing iRFPs in BALB/C nude mice in vivo

Grayscale-to-Color: Scalable Fabrication of Custom Multispectral Filter Arrays.

Snapshot multispectral image (MSI) sensors have been proposed as a key enabler for a plethora of multispectral imaging applications, from diagnostic medical imaging to remote sensing. With each application requiring a different set, and number, of spectral bands, the absence of a scalable, cost-effective manufacturing solution for custom multispectral filter arrays (MSFAs) has prevented widespread MSI adoption. Despite recent nanophotonic-based efforts, such as plasmonic or high-index metasurface arrays, large-area MSFA manufacturing still consists of many-layer dielectric (Fabry-Perot) stacks, requiring separate complex lithography steps for each spectral band and multiple material compositions for each. It is an expensive, cumbersome, and inflexible undertaking, but yields optimal optical performance. Here, we demonstrate a manufacturing process that enables cost-effective wafer-level fabrication of custom MSFAs in a single lithographic step, maintaining high efficiencies (∼75%) and narrow line widths (∼25 nm) across the visible to near-infrared. By merging grayscale (analog) lithography with metal-insulator-metal (MIM) Fabry-Perot cavities, whereby exposure dose controls cavity thickness, we demonstrate simplified fabrication of MSFAs up to N-wavelength bands. The concept is first proven using low-volume electron beam lithography, followed by the demonstration of large-volume UV mask-based photolithography with MSFAs produced at the wafer level. Our framework provides an attractive alternative to conventional MSFA manufacture and metasurface-based spectral filters by reducing both fabrication complexity and cost of these intricate optical devices, while increasing customizability

Criteria for the design of tissue-mimicking phantoms for the standardization of biophotonic instrumentation

A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation

Robustness to misalignment of low-cost, compact quantitative phase imaging architectures.

Non-interferometric approaches to quantitative phase imaging could enable its application in low-cost, miniaturised settings such as capsule endoscopy. We present two possible architectures and both analyse and mitigate the effect of sensor misalignment on phase imaging performance. This is a crucial step towards determining the feasibility of implementing phase imaging in a capsule device. First, we investigate a design based on a folded 4f correlator, both in simulation and experimentally. We demonstrate a novel technique for identifying and compensating for axial misalignment and explore the limits of the approach. Next, we explore the implications of axial and transverse misalignment, and of manufacturing variations on the performance of a phase plate-based architecture, identifying a clear trade-off between phase plate resolution and algorithm convergence time. We conclude that while the phase plate architecture is more robust to misalignment, both architectures merit further development with the goal of realising a low-cost, compact system for applying phase imaging in capsule endoscopy

Spectrally tailored 'hyperpixel' filter arrays for imaging of chemical compositions

We present a method for designing and fabricating 'HyperPixels': pixel filter arrays with custom spectral transmission properties that enable efficient imaging of specific chromophores or fluorophores. Multispectral imaging typically targets particular spectral bands to uncover the spectral properties of tissue in combination with spatial resolution. Unmixing spectral properties can uncover the type and quantity of chromophores or fluorophores due to their unique spectral absorption or emission. Pixelated filter arrays atop imaging sensors are low-cost techniques used to achieve multispectral imaging. Typically, the filter pixels exhibit bandpass spectral behaviour, allowing only a fraction of the incident light to reach the sensor. As a result, narrowband filter pixels trade off high spectral resolution with optical power loss. A way to avoid this issue and improve the signal to noise ratio (SNR) for individual targets is to use a filter array where individual pixels are matched to a target chemical compound's reflectance or emission spectrum. Simulations show a > 5-fold improvement in SNR under realistic noise conditions. These matched optical filters can also reduce the complexity of software or hardware spectral unmixing algorithms, offering the potential for real-time imaging of target compounds. We present a method for tailoring spectral transmission of individual pixels by building HyperPixels comprising multiple Fabry-Perot resonator subpixels with varying bandpass properties (FWHM = approximately 50-60 nm, thicknesses 75-150 nm) that collectively have the desired transmission spectrum. We used a numerical optimization process to design filter arrays for simultaneous detection of methylene blue and indocyanine green, commonly used in cancer diagnostics by clinicians. We then fabricated filters for indocyanine green detection using grayscale lithography with pixel sizes down to 5 µm and individual subpixels down to 0.5 µm and characterized them for their spectral properties