Optical tweezers for trapping in a microfluidic environment.

Optical tweezers use the force from a light beam to implement a precise gripping tool. Based purely on an optical principle, it works without any bodily contact with the object. In this paper we describe an optical tweezers that targets an application within the framework of nuclear magnetic resonance (NMR) spectroscopy of small objects, which are embedded inside a microfluidic channel that will be integrated in a micro-NMR detector. In the project's final stages, the whole system will be installed within the wide bore of a superconducting magnet. The aim is to precisely maintain the position of the object to be measured, without the use of susceptibility disturbing materials or geometries. In this contribution we focus on the design and construction of the tweezers. For the optical force simulation of the system we used a geometrical optics approach, which we combined with a ray fan description of the output beam of an optical system. By embedding both techniques within an iterative design process, we were able to design efficient optical tweezers that met the numerous constraints. Based on details of the constraints and requirements given by the application, different system concepts were derived and studied. Next, a highly adapted and efficient optical trapping system was designed and manufactured. After the components were characterized using vertical scanning interferometry, the system was assembled to achieve a monolithic optical component. The proper function of the optical tweezers was successfully tested by optical trapping of fused silica particles.

Improved method for MR microscopy of brain tissue cultured with the interface method combined with Lenz lenses.

MR in microscopy can non-invasively image the morphology of living tissue, which is of particular interest in studying the mammalian brain. Many studies use live animals for basic research on brain functions, disease pathogenesis, and drug development. However, in vitro systems are on the rise, due to advantages such as the absence of a blood-brain barrier, predictable pharmacokinetics, and reduced ethical restrictions. Hence, they present an inexpensive and adequate technique to answer scientific questions and to perform drug screenings. Some publications report the use of acute brain slices for MR microscopy studies, but these only permit single measurements over several hours. Repetitive MR measurements in longitudinal studies demand an MR-compatible setup which allows cultivation for several days or weeks, and hence properly functioning in vitro systems. Organotypic hippocampal slice cultures (OHSC) are a well-established and robust in vitro system which still exhibits most histological hallmarks of the hippocampal network in vivo. An MR compatible incubation platform is introduced in which OHSC are cultivated according to the interface method following Stoppini et al. In this cultivation method a tissue slice is placed onto a membrane with nutrition medium underneath and a gas atmosphere above, where the air-tissue interface perpendicular to the B0 field induces strong artefacts. We introduce a handling protocol that suppresses these artefacts and increases signal quality significantly to acquire high resolution images of tissue slices. An additional challenge is the lack of available of MR microscopy equipment suitable for small animal scanners. A Lenz lens with an attached capacitor can dramatically increase the SNR in these cases, and wirelessly bring the detection system in close proximity to the sample without compromising the OHSC system through the introduction of wired detectors. The resultant signal gain is demonstrated by imaging a PFA-fixed brain slice with a 72 mm diameter volume coil without a Lenz lens, and with a broadband and a self-resonant Lenz lens. In our setting, the self-resonant Lenz lens increases the SNR 10-fold over using the volume coil only.

A microwave resonator integrated on a polymer microfluidic chip.

We describe a novel stacked split-ring type microwave (MW) resonator that is integrated into a 10mm by 10mm sized microfluidic chip. A straightforward and scalable batch fabrication process renders the chip suitable for single-use applications. The resonator volume can be conveniently loaded with liquid sample via microfluidic channels patterned into the mid layer of the chip. The proposed MW resonator offers an alternative solution for compact in-field measurements, such as low-field magnetic resonance (MR) experiments requiring convenient sample exchange. A microstrip line was used to inductively couple MWs into the resonator. We characterised the proposed resonator topology by electromagnetic (EM) field simulations, a field perturbation method, as well as by return loss measurements. Electron paramagnetic resonance (EPR) spectra at X-band frequencies were recorded, revealing an electron-spin sensitivity of 3.7·10(11)spins·Hz(-1/2)G(-1) for a single EPR transition. Preliminary time-resolved EPR experiments on light-induced triplet states in pentacene were performed to estimate the MW conversion efficiency of the resonator.

Polydimethylsiloxane bilayer films with an embedded spontaneous curvature.

Elastomer polydimethylsiloxane (PDMS) films with embedded in-plane gradient stress are created by making PDMS/(PDMS + silicone oil) crosslinked bilayers and extracting the oil in a suitable organic solvent bath. The collapse of the elastomer after oil extraction generates differential stress in the films that is manifested through their out-of-plane deformation. The curvature κ of narrow stripes of the bilayer, which is composed of layers of approximately equal thicknesses and elasticity moduli, is satisfactorily described by the simple relationship κ = 1.5δH(-1), where δ is the mechanical strain, and H is the total thickness of the bilayer. Curvature mapping of triangular PDMS plates reveals the existence of spherical and cylindrical types of deformation at different locations of the plates. Various 3D-shaped objects can be formed by the self-folding of appropriately designed 2D patterns that are cut from the films, or by nonuniform distribution of the collapsing layer. Thin PDMS bilayers with embedded stress roll up into microtubes of almost perfect cylindrical shape when released in a controlled manner from a substrate.

Phased-array of microcoils allows MR microscopy of ex vivo human skin samples at 9.4 T.

PURPOSE: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology. MATERIALS AND METHODS: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo. RESULTS: In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high-resolution MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high-resolution images with in-plane resolution up to 25 × 25 µm², and 100 µm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle. CONCLUSION: This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non-invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology.

4D flow magnetic resonance imaging in bicuspid aortic valve disease demonstrates altered distribution of aortic blood flow helicity.

PURPOSE: Changes in aortic geometry or presence of aortic valve (AoV) disease can result in substantially altered aortic hemodynamics. Dilatation of the ascending aorta or AoV abnormalities can result in an increase in helical flow. METHODS: 4D flow magnetic resonance imaging was used to test the feasibility of quantitative helicity analysis using equidistantly distributed 2D planes along the entire aorta. The evaluation of the method included three parts: (1) the quantification of helicity in 12 healthy subjects, (2) an evaluation of observer variability and test-retest reliability, and (3) the quantification of helical flow in 16 patients with congenitally altered bicuspid AoVs. RESULTS: Helicity quantification in healthy subjects revealed consistent directions of flow rotation along the entire aorta with high clockwise helicity in the aortic arch and an opposite rotation sense in the ascending and descending aorta. The results demonstrated good scan-rescan and inter- and intraobserver agreement of the helicity parameters. Helicity quantification in patients revealed a significant increase in absolute peak relative helicity during systole and a considerably greater heterogeneous distribution of mean helicity in the aorta. CONCLUSION: The method has the potential to serve as a reference distribution for comparisons of helical flow between healthy subjects and patients or between different patient groups.

Closed circuit MR compatible pulsatile pump system using a ventricular assist device and pressure control unit.

The aim of this study was to evaluate the performance of a closed circuit MR compatible pneumatically driven pump system using a ventricular assist device as pulsatile flow pump for in vitro 3D flow simulation. Additionally, a pressure control unit was integrated into the flow circuit. The performance of the pump system and its test-retest reliability was evaluated using a stenosis phantom (60% lumen narrowing). Bland-Altman analysis revealed a good test-retest reliability (mean differences = -0.016 m/s, limits of agreement = ±0.047 m/s) for in vitro flow measurements. Furthermore, a rapid prototyping in vitro model of a normal thoracic aorta was integrated into the flow circuit for a direct comparison of flow characteristics with in vivo data in the same subject. The pneumatically driven ventricular assist device was attached to the ascending aorta of the in vitro model to simulate the beating left ventricle. In the descending part of the healthy aorta a flexible stenosis was integrated to model an aortic coarctation. In vivo and in vitro comparison showed significant (P = 0.002) correlations (r = 0.9) of mean velocities. The simulation of increasing coarctation grade led to expected changes in the flow patterns such as jet flow in the post-stenotic region and increased velocities.

Characterization of a 3D MEMS fabricated micro-solenoid at 9.4 T.

We present for the first time a complete characterization of a micro-solenoid for high resolution MR imaging of mass- and volume-limited samples based on three-dimensional B(0), B(1) per unit current (B(1)(unit)) and SNR maps. The micro-solenoids are fabricated using a fully micro-electromechanical systems (MEMS) compatible process in conjunction with an automatic wire-bonder. We present 15 µm isotropic resolution 3D B(0) maps performed using the phase difference method. The resulting B(0) variation in the range of [-0.07 ppm to -0.157 ppm] around the coil center, compares favorably with the 0.5 ppm limit accepted for MR microscopy. 3D B(1)(unit) maps of 40 µm isotropic voxel size were acquired according to the extended multi flip angle (ExMFA) method. The results demonstrate that the characterized microcoil provides a high and uniform sensitivity distribution around its center (B(1)(unit) = 3.4 mT/A ± 3.86%) which is in agreement with the corresponding 1D theoretical data computed along the coil axis. The 3D SNR maps reveal a rather uniform signal distribution around the coil center with a mean value of 53.69 ± 19%, in good agreement with the analytical 1D data along coil axis in the axial slice. Finally, we prove the microcoil capabilities for MR microscopy by imaging Eremosphaera viridis cells with 18 µm isotropic resolution.