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Fossil teeth are primary tools in the study of vertebrate evolution, but standard imaging modalities have not been capable of providing high-quality images in dentin, the main component of teeth, owing to small refractive index differences in the fossilized dentin. Our first attempt to use third-harmonic generation (THG) microscopy in fossil teeth has yielded significant submicrometer level anatomy, with an unexpectedly strong signal contrasting fossilized tubules from the surrounding dentin. Comparison between fossilized and extant teeth of crocodilians reveals a consistent evolutionary signature through time, indicating the great significance of THG microscopy in the evolutionary studies of dental anatomy in fossil teeth.

Clear 3D visualization in fossilized dentinal tissues was first discovered with extremely strong contrast by means of third harmonic generation microscopy, providing a novel approach to study the dental evolution of ancient vertebrates (dinosaurs) noninvasively.

The demand for functional imaging in clinical medicine is comprehensive. Although the gold standard for the functional imaging of human bones in clinical settings is still radionuclide-based imaging modalities, nonionizing noninvasive imaging technology in small animals has greatly advanced in recent decades, especially the diffuse optical imaging to which Britton Chance made tremendous contributions. The evolution of imaging probes, instruments, and computation has facilitated exploration in the complicated biomedical research field by allowing longitudinal observation of molecular events in live cells and animals. These research-imaging tools are being used for clinical applications in various specialties, such as oncology, neuroscience, and dermatology. The Bone, a deeply located mineralized tissue, presents a challenge for noninvasive functional imaging in humans. Using nanoparticles (NP) with multiple favorable properties as bioimaging probes has provided orthopedics an opportunity to benefit from these noninvasive bone-imaging techniques. This review highlights the historical evolution of radionuclide-based imaging, computed tomography, positron emission tomography, and magnetic resonance imaging, diffuse optics–enabled in vivo technologies, vibrational spectroscopic imaging, and a greater potential for using NPs for biomedical imaging.

Silicon-On-Insulator (SOI) based nanowire field-effect-transistors were used to detect the molecular charges on the wire surface. The sensors hold great potential for various biomedical applications (Li et al., 2004) due to their intrinsic advantages in many aspects including high sensitivity with minimal requirement of the target molecules, capability for multiplex parallel processing, and requiring no tedious sample labeling process. The variations of the molecular charges can be detected by measuring the changes of the wire conductance. In this work, we show that when incorporated with surface APTES molecules, the SOI-based silicon nanowires can act as a detector for DNA-hybridization. The high charge sensitivity of the nanowires allowed real time detection of hybridization of ssDNA with lengths as short as 15 mer, and with high degree of specificity. Details about device and microfluidic channel fabrication processes, and procedures for surface modification, DNA immobilization are provided in the following sections.

Spectral dependent values of the third-harmonic-generation susceptibility chi(3)(3omega:omega,omega,omega) of Ag-nanoparticles have been successfully determined. When the third-harmonic-generation wavelength coincides with the Ag-nanoparticlespsila plasmon-resonant frequency, strong chi(3)(3omega:omega,omega,omega) enhancement is experimentally proved for the first time.

The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses.