Bioinspired, vertically stacked, and perovskite nanocrystal-enhanced CMOS imaging sensors for resolving UV spectral signatures.

Imaging and identifying target signatures and biomedical markers in the ultraviolet (UV) spectrum is broadly important to medical imaging, military target tracking, remote sensing, and industrial automation. However, current silicon-based imaging sensors are fundamentally limited because of the rapid absorption and attenuation of UV light, hindering their ability to resolve UV spectral signatures. Here, we present a bioinspired imaging sensor capable of wavelength-resolved imaging in the UV range. Inspired by the UV-sensitive visual system of the Papilio xuthus butterfly, the sensor monolithically combines vertically stacked photodiodes and perovskite nanocrystals. This imaging design combines two complementary UV detection mechanisms: The nanocrystal layer converts a portion of UV signals into visible fluorescence, detected by the photodiode array, while the remaining UV light is detected by the top photodiode. Our label-free UV fluorescence imaging data from aromatic amino acids and cancer/normal cells enables real-time differentiation of these biomedical materials with 99% confidence.

The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas.

BACKGROUND: With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma. METHODS: Before surgery, 30 patients with an indeterminate pulmonary nodule were intravenously administered a folate receptor-targeted fluorescent contrast agent specific for primary lung adenocarcinomas. During surgery, the nodule was removed and the presence of fluorescence (optical biopsy) was assessed in the operating room to determine if the nodule was a primary pulmonary adenocarcinoma. Standard-of-care frozen section and immunohistochemical staining on permanent sections were then performed as the gold standard to validate the results of the optical biopsy. RESULTS: Optical biopsies identified 19 of 19 (100%) primary pulmonary adenocarcinomas. There were no false positive or false negative diagnoses. An optical biopsy required 2.4 minutes compared to 26.5 minutes for frozen section (P < 0.001) and it proved more accurate than frozen section in diagnosing lung adenocarcinomas. CONCLUSIONS: An optical biopsy has excellent positive predictive value for intraoperative diagnosis of primary lung adenocarcinomas. With refinement, this technology may prove to be an important supplement to standard pathology for examining close surgical margins, identifying lymph node involvement, and determining whether suspicious nodules are malignant.

Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect.

Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by noninvasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine.

A new class of far-red and near-infrared biological labels based on alloyed semiconductor quantum dots.

Ternary cadmium selenium telluride quantum dots (CdSe(1-x)Tex, x = mole fraction of tellurium) have been prepared for potential use as constant-size biolabels with tunable fluorescence emission in the far-red and near-infrared (650-850 nm) spectral range. In contrast to particle size tuning reported for binary dots, we show that molar composition can be used to tune the optical and electronic properties of alloyed semiconductor nanocrystals without changing the particle size. A surprising finding is a nonlinear relationship between the composition and the absorption/emission energies, leading to new properties not obtainable from the parent CdSe and CdTe binary systems. Coating the alloy cores with a higher band-gap material such as CdS improves the fluorescence efficiencies to about 40-60% at room temperature and allows the preparation of water-soluble and biocompatible alloyed dots at similar quantum yields. A cadmium-rich surface is found to improve mercapto ligand binding and the long-term stability of water-soluble dots.

Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding.

Semiconductor nanoparticles in the size range of 2-6 nm are of great current interest, not only because of their size-tunable properties but also because of their dimensional similarity with biological macromolecules (e.g., nucleic acids and proteins). This similarity could allow an integration of nanomaterials with biological molecules, which would have applications in medical diagnostics, targeted therapeutics, and high-throughput drug screening. Here we report new developments in preparing highly luminescent and biocompatible CdSe quantum dots (QDs), and in synthesizing QD-encoded micro- and nano-beads in the size range of 100 nm-10 microm. We show that the optical properties of ZnS-capped CdSe quantum dots are sensitive to environmental factors such as pH and divalent cations, leading to the potential use of quantum dots in molecular sensing. We also show that chemically modified proteins can be used to coat the surface of water-soluble QDs, to restore their fluorescence, and to provide functional groups for bioconjugation. For multiplexed optical encoding, we have prepared large microbeads with sizes similar to that of mammalian cells, and small nanobeads with sizes similar to that of viruses.