Metamaterials have attracted intensive research interest in recent years because their optical properties have a strong dependence on the geometry of metamaterial molecules rather than the material composition. [1][2][3] This feature has inspired the creation and tailoring of exotic properties, such as a negative refractive index, [ 4 , 5 ] perfect absorption, [ 6 ] and super lensing, [ 7 , 8 ] which are not readily available in nature. For many practical applications such as data storage [ 9 ] and optical switching, [ 10 ] switchable metamaterials that possess very different states are almost a necessity. [ 11 ] Most of the tunable metamaterials that have been demonstrated rely on tuning constituent materials or changing surrounding media by introducing natural materials with higher tunability, such as liquid crystals and phase changing materials. [12][13][14][15][16][17][18][19] However, this limits the choices of materials and becomes increasingly diffi cult to implement at higher frequencies. Moreover, the tuning range is usually too limited to achieve a switching effect between strikingly different states.A complementary approach is to mechanically reconfi gure the metamaterial molecules. [ 20 , 21 ] Micromachining technology has been developed for fabrication and actuation of micromechanical devices [22][23][24][25][26] with switching frequencies up to the GHz level. [ 27 ] An attempt was made to adjust the distance between several planar metamaterial layers in which effi cient transmission change was achieved but the tuning originated from a change in the layer structure rather than a change in metamaterial molecule. [ 22 ] Recently, another interesting work demonstrated the modifi cation of the optical properties of a metamaterial by reorienting the metamaterial molecules. [ 23 ] Inspired by these prior studies, we report the concept and design of switchable magnetic metamaterials by directly reshaping the metamaterial molecules using the micromachining technology and present working devices with switchable magnetic responses.The schematic diagram of the switchable magnetic metamaterial is shown in Figure 1 a. Each metamaterial molecule consists of two semi-square split rings. One is anchored on the substrate while the other can be moved by micromachined actuators. As a result, the gap between the split rings can be altered and thus the geometric shape of the metamaterial molecule can be changed. Figure 1 b-d illustrates the two semi-square spit rings in different states. In Figure 1 b, the two split rings are separated by a small gap, resulting in a geometric shape "[]". This is a typical split ring resonator. [ 28 ] For simple notation, this state is called the open-ring state. Figure 1 c,d show two extreme cases. In the former, the gap between the two split rings is closed and the actual metamaterial molecule becomes a closed ring in the "ٗ" shape. This is called the closed-ring state. In the latter, the movable ring is moved away until it touches the back side of the fi xed ring in the next metama...
A micromachined reconfigurable metamaterial is presented, whose unit cell consists of a pair of asymmetric split‐ring resonators (ASRRs); one is fixed to the substrate while the other is patterned on a movable frame. The reconfigurable metamaterial and the supporting structures (e.g., microactuators, anchors, supporting frames, etc.) are fabricated on a silicon‐on‐insulator wafer using deep reactive‐ion etching (DRIE). By adjusting the distance between the two ASRRs, the strength of dipole–dipole coupling can be tuned continuously using the micromachined actuators and this enables tailoring of the electromagnetic response. The reconfiguration of unit cells endows the micromachined reconfigurable metamaterials with unique merits such as electromagnetic response under normal incidence and wide tuning of resonant frequency (measured as 31% and 22% for transverse electric polarization and transverse magnetic polarization, respectively). The reconfiguration could also allow switching between the polarization‐dependent and polarization‐independent states. With these features, the micromachined reconfigurable metamaterials may find potential applications in transformation optics devices, sensors, intelligent detectors, tunable frequency‐selective surfaces, and spectral filters.
Direct monitoring of cell death (i.e., apoptosis and necrosis) during or shortly after treatment is desirable in all cancer therapies to determine the outcome. Further differentiation of apoptosis from necrosis is crucial to optimize apoptosis-favored treatment protocols. We investigated the potential modality of using tissue intrinsic fluorescence chromophore, reduced nicotinamide adenine dinucleotide (NADH), for cell death detection. We imaged the fluorescence lifetime changes of NADH before and after staurosporine (STS)-induced mitochondria-mediated apoptosis and hydrogen peroxide (H2O2)-induced necrosis, respectively, using two-photon fluorescence lifetime imaging in live HeLa cells and 143B osteosarcoma. Time-lapsed lifetime images were acquired at the same site of cells. In untreated cells, the average lifetime of NADH fluorescence was approximately 1.3 ns. The NADH average fluorescence lifetime increased to approximately 3.5 ns within 15 min after 1 microM STS treatment and gradually decreased thereafter. The NADH fluorescence intensity increased within 15 min. In contrast, no significant dynamic lifetime change was found in cells treated with 1 mM H2O2. Our findings suggest that monitoring the NADH fluorescence lifetime may be a valuable noninvasive tool to detect apoptosis and distinguish apoptosis from necrosis for the optimization of apoptosis-favored treatment protocols and other clinical applications.
Abstract. The metabolic changes of human mesenchymal stem cells ͑hMSCs͒ during osteogenic differentiation were accessed by reduced nicotinamide adenine dinucleotide ͑NADH͒ fluorescence lifetime. An increase in mean fluorescence lifetime and decrease in the ratio between free NADH and protein-bound NADH correlated with our previously reported increase in the adenosine triphosphate ͑ATP͒ level of hMSCs during differentiation. These findings suggest that NADH fluorescence lifetime may serve as a new optical biomarker for noninvasive selection of stem cells from differentiated progenies. Keywords: microscopy; fluorescence lifetime; stem cell.Paper 08176L received Jun. 5, 2008; accepted for publication Aug. 14, 2008; published online Oct. 9, 2008. Stem cells give rise to tissue progenitor cells, which can differentiate into specific progenies and have potential use in regenerative medicine, disease treatment, and developmental biology. Efforts have been made to search for reliable biomarkers to identify stem cells ex vivo 1 and in vivo 2 so as to gain a better insight into the biology and physiology of stem cells, as well as to increase the selection efficiency from a given cell pool. However, many of the markers are invasive even in in vivo imaging approaches because stem cells were preloaded ex vivo by radionuclide, ferromagnetic, or reporter labeling, 2 which decreases the clinical usefulness of these methods. Recently, a noninvasive biomarker using proton nuclear magnetic resonance spectroscopy ͑ 1 H-MRS͒ has been identified for detection of neural stem and progenitor cells in the human brain in vivo.3 Although the identity of this 1 H-MRS-detected biomarker is not known, it is suggestive of a metabolic profile of fatty acids. In fact, one generally accepted property of stem cells that differs from their differentiated progenies is a lower metabolic rate accompanied by a lower adenosine triphosphate ͑ATP͒ content. 4 The shift from anaerobic glycolysis to the more efficient mitochondrial oxidative metabolism has been demonstrated in the differentiation of cardiomyocytes 5 and human mesenchymal stem cells ͑hMSCs͒. 6 The preference of stem cells to produce energy by glycolysis instead of oxidative phosphorylation is similar to that of cancer cells, which has been termed the Warburg effect.Optical detection/imaging techniques have been employed to study cell metabolism in a noninvasive manner by monitoring the intrinsic fluorescence signal of reduced nicotinamide adenine dinucleotide ͑NADH͒, a key coenzyme in glycolysis and oxidative metabolism. Two measurement schemes are possible: fluorescence lifetime 7 and fluorescence intensity. 8 In the fluorescence lifetime measurement scheme, a fluorescence decay curve is typically fitted to a twocomponent exponential decay function F͑t͒ = a 1 exp͑−t / 1 ͒ + a 2 exp͑−t / 2 ͒, where 1 and 2 correspond to the short and long fluorescence lifetimes of NADH and were reported to be ϳ400 to 500 ps and ϳ2000 to 2500 ps for free and bound NADH, respectively.7 a 1 and a 2 are the c...
We experimentally demonstrated a polarization dependent state to polarization independent state change in terahertz (THz) metamaterials. This is accomplished by reconfiguring the lattice structure of metamaterials from 2-fold to 4-fold rotational symmetry by using micromachined actuators. In experiment, it measures resonance frequency shift of 25.8% and 12.1% for TE and TM polarized incidence, respectively. Furthermore, single-band to dual-band switching is also demonstrated. Compared with the previous reported tunable metamaterials, lattice reconfiguration promises not only large tuning range but also changing of polarization dependent states, which can be used in photonic devices such as sensors, optical switches, and filters. V
Alzheimer's disease is the leading cause of dementia. The long progression period in Alzheimer's disease provides a possibility for patients to get early treatment by having routine screenings. However, current clinical diagnostic imaging tools do not meet the specific requirements for screening procedures due to high cost and limited availability. In this work, we took the initiative to evaluate the retina, especially the retinal vasculature, as an alternative for conducting screenings for dementia patients caused by Alzheimer's disease. Highly modular machine learning techniques were employed throughout the whole pipeline. Utilizing data from the UK Biobank, the pipeline achieved an average classification accuracy of 82.44%. Besides the high classification accuracy, we also added a saliency analysis to strengthen this pipeline's interpretability. The saliency analysis indicated that within retinal images, small vessels carry more information for diagnosing Alzheimer's diseases, which aligns with related studies.
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