A portable elliptical dichroism spectrometer targeting secondary structural features of tumorous protein for pancreatic cancer detection.

Stereochemical analysis is essential for understanding the complex function of biomolecules. Various direct and indirect approaches can be used to explore the allosteric configuration. However, the size, cost, and delicate nature of these systems limit their biomedical usage. Here, we constructed elliptical dichroism (ED) spectrometer for biomedical applications, whose performance is validated by experiment and theoretical simulation (Jones/Mueller calculus and time-dependent density-functional theory). Instead of complicated control of circular polarization, ED spectrometer adopted the absorbance of left- and right-oriented elliptically polarized light. With a simplified design, we demonstrated the potential of ED spectrometry as an alternative for secondary structural analysis of biomolecules, their conformation and chirality. It not only provides a portable, low-cost alternative to the sophisticated instruments currently used for structural analysis of biomolecules but also provides superior translational features: low sample consumption(200 µl), easy operation, and multiple working modes, for noninvasive cancer detection.

Nucleotide Identification in DNA Using Dielectrophoresis Spectroscopy.

We show that negative dielectrophoresis (DEP) spectroscopy is an effective transduction mechanism of a biosensor for the detection of single nucleotide polymorphism (SNP) in a short DNA strand. We observed a frequency dependence of the negative DEP force applied by interdigitated electrodes to polystyrene microspheres (PM) with respect to changes in both the last and the second-to-last nucleotides of a single-strand DNA bound to the PM. The drift velocity of PM functionalized to single-strand DNA, which is proportional to the DEP force, was measured at the frequency range from 0.5 MHz to 2 MHz. The drift velocity was calculated using a custom-made automated software using real time image processing technique. This technology for SNP genotyping has the potential to be used in the diagnosis and the identification of genetic variants associated with diseases.

Integrated dielectrophoretic and surface plasmonic platform for million-fold improvement in the detection of fluorescent events.

We present an integrated dielectrophoretic (DEP) and surface plasmonic technique to quantify ∼1 pM of fluorescent molecules in low conductivity buffers. We have established a DEP force on target molecules to bring those molecules and place them on the nanometallic structures (hotspots) for quantification through surface plasmonic effects. Our results show that the DEP is capable of placing the fluorescent molecules on the hotspots, which are depicted as a significant reduction in the fluorescence lifetime of those molecules. To efficiently integrate the DEP and plasmonic effects, we have designed and utilized pearl-shaped interdigitated electrodes (PIDEs) in experiments. These electrodes generate 2-3 times higher DEP force than traditional interdigitated electrodes. Therefore, high-throughput assays can be developed. The nanometallic structures were strategically fabricated in the periphery of PIDEs for smooth integration of DEP and plasmonic detection. With the introduction of DEP, about 106-fold improvement was achieved over existing plasmonic-based detection. Therefore, this simple addition to the existing surface plasmonic-based detection will enable the disease related protein detection.

Massively parallel simulator of optical coherence tomography of inhomogeneous turbid media.

BACKGROUND AND OBJECTIVE: An accurate and practical simulator for Optical Coherence Tomography (OCT) could be an important tool to study the underlying physical phenomena in OCT such as multiple light scattering. Recently, many researchers have investigated simulation of OCT of turbid media, e.g., tissue, using Monte Carlo methods. The main drawback of these earlier simulators is the long computational time required to produce accurate results. We developed a massively parallel simulator of OCT of inhomogeneous turbid media that obtains both Class I diffusive reflectivity, due to ballistic and quasi-ballistic scattered photons, and Class II diffusive reflectivity due to multiply scattered photons. METHODS: This Monte Carlo-based simulator is implemented on graphic processing units (GPUs), using the Compute Unified Device Architecture (CUDA) platform and programming model, to exploit the parallel nature of propagation of photons in tissue. It models an arbitrary shaped sample medium as a tetrahedron-based mesh and uses an advanced importance sampling scheme. RESULTS: This new simulator speeds up simulations of OCT of inhomogeneous turbid media by about two orders of magnitude. To demonstrate this result, we have compared the computation times of our new parallel simulator and its serial counterpart using two samples of inhomogeneous turbid media. We have shown that our parallel implementation reduced simulation time of OCT of the first sample medium from 407 min to 92 min by using a single GPU card, to 12 min by using 8 GPU cards and to 7 min by using 16 GPU cards. For the second sample medium, the OCT simulation time was reduced from 209 h to 35.6 h by using a single GPU card, and to 4.65 h by using 8 GPU cards, and to only 2 h by using 16 GPU cards. Therefore our new parallel simulator is considerably more practical to use than its central processing unit (CPU)-based counterpart. CONCLUSIONS: Our new parallel OCT simulator could be a practical tool to study the different physical phenomena underlying OCT, or to design OCT systems with improved performance.

Negative dielectrophoresis spectroscopy for rare analyte quantification in biological samples.

We propose the use of negative dielectrophoresis (DEP) spectroscopy as a technique to improve the detection limit of rare analytes in biological samples. We observe a significant dependence of the negative DEP force on functionalized polystyrene beads at the edges of interdigitated electrodes with respect to the frequency of the electric field. We measured this velocity of repulsion for 0% and 0.8% conjugation of avidin with biotin functionalized polystyrene beads with our automated software through real-time image processing that monitors the Rayleigh scattering from the beads. A significant difference in the velocity of the beads was observed in the presence of as little as 80 molecules of avidin per biotin functionalized bead. This technology can be applied in the detection and quantification of rare analytes that can be useful in the diagnosis and the treatment of diseases, such as cancer and myocardial infarction, with the use of polystyrene beads functionalized with antibodies for the target biomarkers.

Monte Carlo simulation of optical coherence tomography for turbid media with arbitrary spatial distributions.

We developed a Monte Carlo-based simulator of optical coherence tomography (OCT) imaging for turbid media with arbitrary spatial distributions. This simulator allows computation of both Class I diffusive reflectance due to ballistic and quasiballistic scattered photons and Class II diffusive reflectance due to multiple scattered photons. It was implemented using a tetrahedron-based mesh and importance sampling to significantly reduce computational time. Our simulation results were verified by comparing them with results from two previously validated OCT simulators for multilayered media. We present simulation results for OCT imaging of a sphere inside a background slab, which would not have been possible with earlier simulators. We also discuss three important aspects of our simulator: (1) resolution, (2) accuracy, and (3) computation time. Our simulator could be used to study important OCT phenomena and to design OCT systems with improved performance.

Fast calculation of multipath diffusive reflectance in optical coherence tomography.

We show how to efficiently calculate the signal in optical coherence tomography (OCT) systems due to the ballistic photons, the quasi-ballistic photons, and the photons that undergo multiple diffusive scattering using Monte Carlo simulations with importance sampling. This method enables the calculation of these three components of the OCT signal with less than one hundredth of the computational time required by the conventional Monte Carlo method. Therefore, it can be used as a design tool to characterize the performance of OCT systems, and can also be used in the development of novel signal processing techniques that can extend the imaging range of OCT systems. We investigate the parameter dependence of our importance sampling method and we validate it by comparison to an existing method.

Improved importance sampling for Monte Carlo simulation of time-domain optical coherence tomography.

We developed an importance sampling based method that significantly speeds up the calculation of the diffusive reflectance due to ballistic and to quasi-ballistic components of photons scattered in turbid media: Class I diffusive reflectance. These components of scattered photons make up the signal in optical coherence tomography (OCT) imaging. We show that the use of this method reduces the computation time of this diffusive reflectance in time-domain OCT by up to three orders of magnitude when compared with standard Monte Carlo simulation. Our method does not produce a systematic bias in the statistical result that is typically observed in existing methods to speed up Monte Carlo simulations of light transport in tissue. This fast Monte Carlo calculation of the Class I diffusive reflectance can be used as a tool to further study the physical process governing OCT signals, e.g., obtain the statistics of the depth-scan, including the effects of multiple scattering of light, in OCT. This is an important prerequisite to future research to increase penetration depth and to improve image extraction in OCT.

Autocorrelation function for polarization mode dispersion emulators with rotators.

We derive a recursion relation for the frequency autocorrelation function of the polarization dispersion vector for polarization mode dispersion emulators with rotators. The autocorrelation function has a nonzero background for an emulator with a fixed number of sections. This background diminishes slowly as the number of sections grows. Randomizing the section lengths removes the autocorrelation periodicity exhibited by an emulator with equal sections, but it does not remove the finite background.