Digant P. Dave

Detection of neural activity using phase-sensitive optical low-coherence reflectometry

We demonstrate non-contact sub-nanometer optical measurement of neural surface displacement associated with action potential propagation. Experimental results are recorded from nerve bundles dissected from crayfish walking leg using a phase-sensitive optical low coherence reflectometer. No exogenous chemicals or reflection coatings are applied. Transient neural surface displacement is less than 1 nm in amplitude, 1 ms in duration and is coincident with action potential arrival to the optical measurement site. Because the technique uses back-reflected light, noninvasive detection of various neuropathies may be possible.

Polarization-maintaining fiber-based optical low-coherence reflectometer for characterization and ranging of birefringence

We describe a polarization-maintaining fiber-based polarization-sensitive optical low-coherence reflectometer for measurement of depth-resolved birefringence. Unlike for other fiber-based polarization-sensitive optical low-coherence reflectometers, here the linear birefringence of a sample can be measured from data recorded in a single A scan. Simultaneous measurement of retardation and orientation of birefringent axes with mica wave plates is demonstrated. The measured retardation is insensitive to sample rotation in the plane perpendicular to ranging.

Doppler-angle measurement in highly scattering media

We describe a dual-channel optical low-coherence reflectometer for accurate measurement of Doppler angles in highly scattering media. Accurate fluid-flow velocity estimation requires measurement of the Doppler shift and angle. Estimated values of the Doppler angle and average fluid-flow velocity from experimental data are in good agreement with preset values.

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

Neuro-optical microfluidic platform to study injury and regeneration of single axons

We describe a neuro-optical microfluidic platform for studying injury and subsequent regeneration of individual mammalian axons. This platform consists of three components integrated on an inverted microscope, which include a compartmentalized neuronal culture microfluidic device, a femtosecond laser to enable precise axotomy, and a custom built mini cell culture incubator for continuous long term observation of post injury events. We demonstrate the unique capabilities of the platform by injuring individual central and peripheral nervous system axons and monitoring the post injury sequence of events from initial degeneration to subsequent regeneration. This platform will enable study and understanding of neuronal response to injury that is currently not possible with conventional cell culture platform and tools.

Gold nanotags for combined multi-colored Raman spectroscopy and x-ray computed tomography

Multi-color gold-nanoparticle-based tags (nanotags) are synthesized for combined surface-enhanced Raman spectroscopy (SERS) and x-ray computed tomography (CT). The nanotags are synthesized with quasi-spherical gold nanoparticles encoded with a reporter dye (color), each with a unique Raman spectrum. A library of nanotags with six different colors were synthesized for a range of gold nanoparticle sizes and an optimum size has been established to yield the largest SERS intensity and x-ray attenuation that is higher than the iodinated CT contrast agents used in clinics. Proof-of-principle in vivo imaging results with nanotags are presented that, for the first time, demonstrates the combined in vivo dual modality imaging capability of SERS and CT with a single nanoparticle probe.

Optical low-coherence reflectometer for differential phase measurement

A birefringent-fiber-based dual-channel optical low-coherence reflectometer capable of differential phase measurement is described. Phase noise owing to environmental perturbations that is common to both channels is canceled, resulting in accurate measurement of the phase difference between light backscattered from two spatially separated sites. Results are presented that demonstrate the accuracy and sensitivity of the system.

Differential phase optical coherence probe for depth-resolved detection of photothermal response in tissue

We describe a differential phase low-coherence interferometric probe for non-invasive, quantitative imaging of photothermal phenomena in biological materials. Our detection method utilizes principles of optical coherence tomography with differential phase measurement of interference fringe signals. A dual-channel optical low-coherence probe is used to analyse laser-induced thermoelastic and thermorefractive effects in tissue with micrometre axial resolution and nanometre sensitivity. We demonstrate an application of the technique using tissue phantoms and ex-vivo tissue specimens of rodent dorsal skin.

Probabilistic Partial Least Square Regression: A Robust Model for Quantitative Analysis of Raman Spectroscopy Data

Raman spectroscopy has been one of the most sensitive techniques widely used in chemical and pharmaceutical material identification research ever since it is invented based on Raman scattering theory, because of the fingerprints property of Raman signals to different materials. With the latest development of surface enhanced Raman scattering (SERS) nanoparticles, Raman spectroscopy is now used in more and more quantitative analysis applications. But due to the unavoidable instable problem of Raman spectroscopy signal, as well as the high signal dimension and small sample number problem, it is badly in need of a robust and accurate signal quantitative analysis method. Based on Partial Least Square Regression (PLSR) method, Probabilistic PCA and Probabilistic curve-fitting idea, we propose a new Probabilistic-PLSR (PPLSR) model. It explains PLSR from a probabilistic viewpoint and deeply describes the physical meaning of PLSR model. It is a solid foundation to develop more robust and accurate probabilistic PLSR models with Bayesian model in order to solve the over-fitting problem. And since this model adds a regularization term in the matrix of regression coefficients, the estimated result is more robust than PLSR model. We also provide an EM Algorithm to estimate the parameters of the model from sample data. To take fully use of the valuable data, we design two experiments, leave-one out and cross-validation-on-average-signal, on one real Raman spectroscopy signal data set. By comparing with results from traditional Least Square (LS) method and traditional PLSR, we demonstrate PPLSR is more robust and accurate.

Porous Hollow Gold Nanoparticles for Cancer SERS Imaging

Surface enhanced Raman spectroscopy (SERS) is a promising molecular imaging modality capable of simultaneously detecting multiple molecular biomarkers. With the biocompatibility and functionalizability of Au, Au-nanoparticle based Raman tags possess the potential for in vivo SERS cancer biomarker detection. Here, we report the large scale synthesis of a new type of Au nanoparticles, Porous Hollow Au Nanoparticles (PHAuNPs), and demonstrate their potential application as SERS imaging tags. PHAuNPs feature a sub-20 nm porous shell and a 50 nm void core. Such unique morphology enables them to strongly absorb and scatter near infrared lights due to the surface plasmon resonant effect of Au. This makes them particularly suitable for in vivo applications, where NIR wavelengths are considered as a ‘clear window’ for deeper penetration of light. The construction and characterization of PHAuNP-based Raman nanotag, including attachment of Raman dye, pegylation and their stability, are described. Cytotoxicity of Raman nanotags are tested using the radioactive [3H]thymidine incorporation method. The results show that pegylated Raman nanotags are stable and non-toxic and can potentially be used for in vivo applications.