A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45−DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9–19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11–13 µm should be used to challenge the system.
Filtration can achieve circulating tumor cell (CTC) enrichment from blood. Key parameters such as flow-rate, applied pressure, and fixation, vary largely between assays and their influence is not well understood. Here, we used a filtration system, to monitor these parameters and determine their relationships. Whole blood, or its components, with and without spiked tumor cells were filtered through track-etched filters. We characterize cells passing through filter pores by their apparent viscosity; the viscosity of a fluid that would pass with the same flow. We measured a ratio of 5·104∶102∶1 for the apparent viscosities of 15 µm diameter MDA-231 cells, 10 µm white cells and 90 fl red cells passing through a 5 µm pore. Fixation increases the pressure needed to pass cells through 8 µm pores 25-fold and halves the recovery of spiked tumor cells. Filtration should be performed on unfixed samples at a pressure of ∼10 mbar for a 1 cm2 track-etched filter with 5 µm pores. At this pressure MDA-231 cells move through the filter in 1 hour. If fixation is needed for sample preservation, a gentle fixative should be selected. The difference in apparent viscosity between CTC and blood cells is key in optimizing recovery of CTC.
The authors demonstrate a compact optical waveguide modulator based on a Mach-Zehnder interferometer driven by surface acoustic waves. The modulator was monolithically fabricated on GaAs with an active region length of approximately 15 m. It yields peak-to-peak modulation exceeding 90% of the average transmission and operation in the gigahertz frequency range. © 2006 American Institute of Physics. ͓DOI: 10.1063/1.2354411͔ Acousto-optic effects have been used for optical modulation for a long time, with the Bragg cells being probably the best known example. 1 The demand for fast and compact devices together with required phase matching, however, imposes several limitations on conventional acousto-optic devices in future generations of integrated photonics. Therefore, great attention has recently been devoted to alternative concepts for light modulation. A promising approach to increase the operation speed employs all-optical light control, which allows operation down to the subpicosecond time scales. 2 These devices are typically a few hundreds of microns long since they rely on optical nonlinearities that are usually small. An effective approach to reduce device dimensions employs photonic crystals ͑PhCs͒. Examples are thermo-optical switches based on a PhC Mach-Zehnder interferometer ͑MZI͒ with 12-m-long arms on AlGaAs/ GaAs system 3 as well as electro-optical switches based on carrier injection of 80-m-long silicon PhC-MZI. 4 In both cases the switching time is on the order of microseconds. Faster PhC-based all-optical switching devices have been realized in the ͑Al,Ga͒As system by taking advantage of the nonlinear properties of quantum dots embedded in the MZI arms. 5 PhC fabrication, however, requires a sophisticated technology with very strict tolerances.In this letter, we demonstrate a compact and monolithic modulator based on conventional ridge waveguides ͑WGs͒ on GaAs. The modulator consists of a MZI driven by a surface acoustic wave ͑SAW͒ in the gigahertz range, where the length of the interaction region between the acoustic and optical waves ͑the active region͒ is reduced to approximately 15 m. The design used, which is a modified version of the acousto-optic MZI proposed by Gorecki et al.,6 is based on the refractive index modulation of the interferometer arms by the wave fronts of a SAW propagating perpendicularly to the arms. The changes in refractive index are induced by the elasto-optic and electro-optic effects associated with the strain and piezoelectric fields, respectively. For photon energies away from electronic transitions-which is the case discussed here-the elasto-optical effect dominates. 7 The width of the WGs forming the arms is chosen to be much smaller than the acoustic wavelength ͑ SAW ͒ in order to ensure a constant modulation amplitude across the WG width. In our design, we introduce two fundamental modifications to increase the modulation efficiency and reduce the length of the active region. First, we enhance the modulation efficiency by modulating simultaneously both interferom...
We study the transport of spin polarized electrons in n-GaAs using spatially resolved continuous wave Faraday rotation. From the measured steady state distribution, we determine spin relaxation times under drift conditions and, in the presence of strain, the induced spin splitting from the observed spin precession. Controlled variation of strain along [110] allows us to deduce the deformation potential causing this effect, while strain along [100] has no effect. The electric field dependence of the spin lifetime is explained quantitatively in terms of an increase of the electron temperature.Sufficiently long spin lifetimes and the possibility to manipulate the spin orientation are required for the development of spintronics devices [1]. Electron spin lifetimes τ s in semiconductors have been measured by means of the Hanle effect (depolarization of photoluminescence in a magnetic field) [2], time resolved photoluminescence [3], and time resolved measurements of magneto-optical effects (Faraday / Kerr rotation) [4], which are suitable to measure τ s in the absence of holes. Although future spintronics applications are likely to depend on spin transport, very little attention has been paid to the influence of an electric drift field F on τ s . While the possibility to transport the electron spin over substantial distances in fields up to F = 100 V/cm has been demonstrated several years ago [5], first measurements of τ s in this field range have only been reported recently [7]. Under the influence of strain, spin precession of the drifting electrons [5,6,8] has been observed and even the possibility to generate spin polarized currents without magnetic materials or optical excitation has been demonstrated [7]. However, no theoretical interpretation of the observed spin lifetimes and no quantitative analysis of the influence of strain on the observed spin splitting has been given.In this Letter, we present a method to study the lateral spin transport in thin films of n-doped GaAs under steady state conditions, similar to the experiments reported recently in [8], but with the possibility to determine spin lifetimes and to quantify the influence of strain. By the absorption of circularly polarized light we locally generate a steady-state electron spin polarization and determine the spin drift length L s from the spatial decay of spin polarization along the drift direction, which results from the combined process of electron diffusion, drift and spin relaxation. As this signal can be traced over several 100 µm while the signal varies by up to three orders of magnitude, this cw method allows for accurate measurements of the electric field, doping density and temperature dependence of L s . Knowing the drift velocity v dr , the spin relaxation time τ s can be determined from L s . In the presence of strain, we observe spin precession in addition to the spatial decay. As realistic theoretical pre-0.001 0.01 0.1 1 0.0 -50 0 50 100 150 -1 -0.1 -0.01 -0.001 0.01 0.1 1 0.0 0.5 -50 0 50 100 150 0.01 0.1 1 e F [V/cm] 40 60 80 80 ...
In wide-field fluorescence microscopy, illuminating the specimen with evanescent standing waves increases lateral resolution more than twofold. We report a versatile setup for standing-wave illumination in total internal reflection fluorescence microscopy. An adjustable diffraction grating written on a phase-only spatial light modulator controls the illumination field. Selecting appropriate diffraction orders and displaying a sheared (tilted) diffraction grating allows one to tune the penetration depth in very fine steps. The setup achieves 91 nm lateral resolution for green emission.
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