Characterizing Far-infrared Laser Emissions and the Measurement of Their Frequencies

The generation and subsequent measurement of far-infrared radiation has found numerous applications in high-resolution spectroscopy, radio astronomy, and Terahertz imaging. For about 45 years, the generation of coherent, far-infrared radiation has been accomplished using the optically pumped molecular laser. Once far-infrared laser radiation is detected, the frequencies of these laser emissions are measured using a three-laser heterodyne technique. With this technique, the unknown frequency from the optically pumped molecular laser is mixed with the difference frequency between two stabilized, infrared reference frequencies. These reference frequencies are generated by independent carbon dioxide lasers, each stabilized using the fluorescence signal from an external, low pressure reference cell. The resulting beat between the known and unknown laser frequencies is monitored by a metal-insulator-metal point contact diode detector whose output is observed on a spectrum analyzer. The beat frequency between these laser emissions is subsequently measured and combined with the known reference frequencies to extrapolate the unknown far-infrared laser frequency. The resulting one-sigma fractional uncertainty for laser frequencies measured with this technique is ± 5 parts in 10⁷. Accurately determining the frequency of far-infrared laser emissions is critical as they are often used as a reference for other measurements, as in the high-resolution spectroscopic investigations of free radicals using laser magnetic resonance. As part of this investigation, difluoromethane, CH₂F₂, was used as the far-infrared laser medium. In all, eight far-infrared laser frequencies were measured for the first time with frequencies ranging from 0.359 to 1.273 THz. Three of these laser emissions were discovered during this investigation and are reported with their optimal operating pressure, polarization with respect to the CO₂ pump laser, and strength.     

Terahertz Plasmonic Quantum Cascade Lasers: a Comprehensive Physics Study

Generation of terahertz (THz) radiation has been a hot research topic in recent years. Plasmonic quantum cascade lasers (QCLs) are among the most compact and efficient sources to generate THz radiation. In this paper, we comprehensively study plasmonic QCLs designed based on the antenna-feedback structure to generate efficient radiation about the center frequency of 3 THz. By changing the geometric structure of the plasmonic cavity and using two-dimensional simulation, a minimum loss less than 5.9 cm^?1 is achieved at the lasing frequency. It is also possible to control the orientation of the output beam either vertically or tilted by changing the geometry of the antenna design via chirped or non-chirped grating scheme. Moreover, the output characteristics of the QCL are simulated based on the three-level rate equations through which the dynamics of the laser, as well as the P-I curve, are investigated. Also, the gain spectra for two laser designs (with chirped and non-chirped gratings) are simulated and compared to each other. The results of this paper may provide deep insight into designing efficient laser sources in the THz region.

     

Synchronization of pacemaker cell firing by weak ELF fields: Simulation by a circuit model

Entrainment of output action potentials from repetitively firing pacemaker cells, brought about by regularly spaced excitatory or inhibitory postsynaptic inputs, is a well-known phenomenon. Synchronization of neural firing patterns by extremely low frequency (ELF) external electric fields has also been observed. Whereas current densities of ≈10 A-m⁻² are required for direct excitation of otherwise quiescent neural tissue, much lower peak current densities (≈10⁻² A-m²) have been reported to entrain spontaneously firing molluscan pacemaker cells. We have developed a neural spike generator circuit model that simulates repetitive spike generation by a space clamped patch (area ≈ 10⁻⁷ m²) of excitable membrane subjected to depolarizing current. Picoampere (pA) range variation of DC depolarizing current causes a corresponding smooth variation of neural spike frequency, producing a physiologically realistic stimulus-response (S-R) characteristic. When lower pA range 60 Hz AC current is superposed upon the DC depolarizing current, smooth variation of the S-R characteristic is distorted by subharmonic locking of the spike generator at 30, 20, 15, 12, 10 Hz, and higher order subharmonic frequencies. Although the additional superposition of a physiologically realistic level of “white” current noise, covering the bandwidth 4–200 Hz, suffices to obscure higher order subharmonic locking, locking at 30, 20, and 15 Hz is still clearly evident in the presence of noise. Subharmonic locking is observed at a root mean square AC simulated tissue current density of ≈10⁻⁵ A-m⁻². Bioelectromagnetics 19:92–97, 1998. © 1998 Wiley-Liss, Inc.     

Evaluation of a green laser pointer for flow cytometry.

Flow cytometers typically incorporate expensive lasers with high-quality (TEM00) output beam structure and very stable output power, significantly increasing system cost and power requirements. Red diode lasers minimize power consumption and cost, but limit fluorophore selection. Low-cost DPSS laser pointer modules could possibly offer increased wavelength selection but presumed emission instability has limited their use. A $160 DPSS 532 nm laser pointer module was first evaluated for noise characteristics and then used as the excitation light source in a custom-built flow cytometer for the analysis of fluorescent calibration and alignment microspheres. Eight of ten modules tested were very quiet (RMS noise < or = 0.6% between 0 and 5 MHz). With a quiet laser pointer module as the light source in a slow-flow system, fluorescence measurements from alignment microspheres produced CVs of about 3.3%. Furthermore, the use of extended transit times and < or =1 mW of laser power produced both baseline resolution of all 8 peaks in a set of Rainbow microspheres, and a detection limit of <20 phycoerythrin molecules per particle. Data collected with the transit time reduced to 25 micros (in the same instrument but at 2.4 mW laser output) demonstrated a detection limit of approximately 75 phycoerythrin molecules and CVs of about 2.7%. The performance, cost, size, and power consumption of the tested laser pointer module suggests that it may be suitable for use in conventional flow cytometry, particularly if it were coupled with cytometers that support extended transit times.     

Automatic verification of SSD and generation of respiratory signal with lasers in radiotherapy: A preliminary study

PurposeSource to surface distance (SSD) plays a very important role in external beam radiotherapy treatment verification. In this study, a simple technique has been developed to verify the SSD automatically with lasers. The study also suggests a methodology for determining the respiratory signal with lasers.MethodsTwo lasers, red and green are mounted on the collimator head of a Clinac 2300 C/D linac along with a camera to determine the SSD. A software (SSDLas) was developed to estimate the SSD automatically from the images captured by a 12-megapixel camera. To determine the SSD to a patient surface, the external body contour of the central axis transverse computed tomography (CT) cut is imported into the software. Another important aspect in radiotherapy is the generation of respiratory signal. The changes in the lasers separation as the patient breathes are converted to produce a respiratory signal. Multiple frames of laser images were acquired from the camera mounted on the collimator head and each frame was analyzed with SSDLas to generate the respiratory signal.ResultsThe SSD as observed with the ODI on the machine and SSD measured by the SSDlas software was found to be within the tolerance limit. The methodology described for generating the respiratory signals will be useful for the treatment of mobile tumors such as lung, liver, breast, pancreas etc.ConclusionThe technique described for determining the SSD and the generation of respiratory signals using lasers is cost effective and simple to implement.     

Acoustic reflections during rhinometry: spatial resolution and sound loss

The accuracy ofthe acoustic reflections method for the evaluation of human nasalairway geometry is determined by the physical limitations of thetechnique and also by the in vivo deviations from the assumptions ofthe technique. The present study 1)examines the sound loss caused by nonrigidity of the nasal mucosa andviscous loss caused by complex geometry and its influence on theestimation of the acoustic area-distance function;2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathingHe-O₂ during the measurements onaccuracy. Measurements made in eight plastic models, withcavities exactly identical to the "living" nasal cavities,revealed only minor effects of nonrigidity of the nasal mucosa. Thiswas confirmed by an electrical analog model, based on laser vibrometryadmittance measurements of the nasal mucosa, which indicated that theerror in the acoustic measurements caused by wall motion isinsignificant. The complex geometry of the nasal cavity per se (i.e.,departure from circular) showed no significant effects on themeasurements. Low-pass filtering of the signal is necessary to cut offcross modes arising in the nasal cavity. Computer simulations andmeasurements in models showed that the sampling frequency should beapproximately four times the low-pass filtering frequency (i.e., twicethe Nyquist frequency) to avoid influence on the result. No advantagewas found for the the use of He-O₂vs. air in the nasal cavity.

     

Simplified patient-specific renal dosimetry in 177Lu therapy: a proof of concept

PurposeThe aim of this proof-of-concept study is to propose a simplified personalized kidney dosimetry procedure in ¹⁷⁷Lu peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and metastatic prostate cancer. It relies on a single quantitative SPECT/CT acquisition and multiple radiometric measurements executed with a collimated external probe, properly directed on kidneys.MethodsWe conducted a phantom study involving external count-rate measurements in an abdominal phantom setup filled with activity concentrations of ^99mTc, reproducing patient-relevant organ effective half-lives occurring in ¹⁷⁷Lu PRRT. GATE Monte Carlo (MC) simulations of the experiment, using ^99mTc and ¹⁷⁷Lu as sources, were performed. Furthermore, we tested this method via MC on a clinical case of ¹⁷⁷Lu-DOTATATE PRRT with SPECT/CT images at three time points (2, 20 and 70 hrs), comparing a simplified kidney dosimetry, employing a single SPECT/CT and probe measurements at three time points, with the complete MC dosimetry.ResultsThe experimentally estimated kidney half-life with background subtraction applied was compatible within 3% with the expected value. The MC simulations of the phantom study, both with ^99mTc and ¹⁷⁷Lu, confirmed a similar level of accuracy. Concerning the clinical case, the simplified dosimetric method led to a kidney dose estimation compatible with the complete MC dosimetry within 6%, 12% and 2%, using respectively the SPECT/CT at 2, 20 and 70 hrs.ConclusionsThe proposed simplified procedure provided a satisfactory accuracy and would reduce the imaging required to derive the kidney absorbed dose to a unique quantitative SPECT/CT, with consequent benefits in terms of clinic workflows and patient comfort.     

Laser-inflicted Injury of Zebrafish Embryonic Skeletal Muscle

Various experimental approaches have been used in mouse to induce muscle injury with the aim to study muscle regeneration, including myotoxin injections (bupivacaine, cardiotoxin or notexin), muscle transplantations (denervation-devascularization induced regeneration), intensive exercise, but also murine muscular dystrophy models such as the mdx mouse (for a review of these approaches see ¹). In zebrafish, genetic approaches include mutants that exhibit muscular dystrophy phenotypes (such as runzel² or sapje³) and antisense oligonucleotide morpholinos that block the expression of dystrophy-associated genes⁴. Besides, chemical approaches are also possible, e.g. with Galanthamine, a chemical compound inhibiting acetylcholinesterase, thereby resulting in hypercontraction, which eventually leads to muscular dystrophy⁵. However, genetic and pharmacological approaches generally affect all muscles within an individual, whereas the extent of physically inflicted injuries are more easily controlled spatially and temporally¹. Localized physical injury allows the assessment of contralateral muscle as an internal control. Indeed, we recently used laser-mediated cell ablation to study skeletal muscle regeneration in the zebrafish embryo⁶, while another group recently reported the use of a two-photon laser (822 nm) to damage very locally the plasma membrane of individual embryonic zebrafish muscle cells⁷.Here, we report a method for using the micropoint laser (Andor Technology) for skeletal muscle cell injury in the zebrafish embryo. The micropoint laser is a high energy laser which is suitable for targeted cell ablation at a wavelength of 435 nm. The laser is connected to a microscope (in our setup, an optical microscope from Zeiss) in such a way that the microscope can be used at the same time for focusing the laser light onto the sample and for visualizing the effects of the wounding (brightfield or fluorescence). The parameters for controlling laser pulses include wavelength, intensity, and number of pulses.Due to its transparency and external embryonic development, the zebrafish embryo is highly amenable for both laser-induced injury and for studying the subsequent recovery. Between 1 and 2 days post-fertilization, somitic skeletal muscle cells progressively undergo maturation from anterior to posterior due to the progression of somitogenesis from the trunk to the tail^{8, 9}. At these stages, embryos spontaneously twitch and initiate swimming. The zebrafish has recently been recognized as an important vertebrate model organism for the study of tissue regeneration, as many types of tissues (cardiac, neuronal, vascular etc.) can be regenerated after injury in the adult zebrafish^{10, 11}.     

Low-frequency Raman spectra of lysozyme.

New techniques in laser Raman spectroscopy are used to obtain spectra of aqueous solutions of lysozylme for frequency shifts as small as 5 cm^?1. In addition, Raman measurements are made on two crystalline forms of hen egg white lysozyme. The spectra obtained from the solution and from the crystal are found to be similar for frequencies above 100 cm^?1. However, a low-frequency band at 25 cm^?1 observed in crystalline lysozyme is not found in the solution, indicating that this band cannot be attributed to an internal molecular vibration.     

Comparison of three differently shaped ROIs in free breathing breast radiotherapy setup using surface guidance with AlignRT®

BackgroundSetup accuracy within adjuvant radiotherapy of breast cancer treated in free breathing is well studied, but a comparison of the typical regions of interest (ROI) used in surface guided radiation therapy (SGRT) does not exist. The aim of this study was to estimate the setup accuracy obtained with differently shaped ROIs in SGRT.Materials and methodsA total of 573 orthogonal image pairs were analyzed from free breathing breast patients in two groups: positioning using AlignRT^® surface guidance system (Group A, n = 20), and setup using conventional laser and tattoo setup (Group L, n = 20). For SGRT, three different setup ROIs were used: a Breast-shaped, O-shaped and T-shaped (B-O and T-ROI). We evaluated the isocenter-, rotation-, pitch and arm position accuracy and residual errors for the chest wall and shoulder joint in kV orthogonal and tangential setup images with laser- or SGRT-based setup.ResultsLess isocenter variance was found in Group A than in Group L. Rotations and posture errors were larger in group L than in Group A (p ≤ 0.05). Rotation error was smaller with T-shaped ROI than with O- or B-shape (p = 0.01–0.04).ConclusionSetup with AlignRT^® improves reproducibility compared to laser setup. Between the different ROI shapes only small differences were found in the patient posture or the isocenter position in the images. The T-ROI is recommended to set up the chest wall bony structure and an additional B-ROI may be used to fine-tune the soft tissue accuracy.     

Use of ZnO:Tb down‐conversion phosphor for Ag nanoparticle plasmon absorption using a He–Cd ultraviolet laser

Although noble metal nanoparticles (NPs) have attracted some attention for potentially enhancing the luminescence of rare earth ions for phosphor lighting applications, the absorption of energy by NPs can also be beneficial in biological and polymer applications where local heating is desired, e.g. photothermal applications. Strong interaction between incident laser light and NPs occurs only when the laser wavelength matches the NP plasmon resonance. Although lasers with different wavelengths are available and the NP plasmon resonance can be tuned by changing its size and shape or the dielectric medium (host material), in this work, we consider exciting the plasmon resonance of Ag NPs indirectly with a He–Cd UV laser using the down‐conversion properties of Tb³⁺ ions in ZnO. The formation of Ag NPs was confirmed by X‐ray diffraction, transmission electron microscopy and UV–vis diffuse reflectance measurements. Radiative energy transfer from the Tb³⁺ ions to the Ag NPs resulted in quenching of the green luminescence of ZnO:Tb and was studied by means of spectral overlap and lifetime measurements. The use of a down‐converting phosphor, possibly with other rare earth ions, to indirectly couple a laser to the plasmon resonance wavelength of metal NPs is therefore successfully demonstrated and adds to the flexibility of such systems. Copyright © 2016 John Wiley & Sons, Ltd.     

Ultrasensitive radioisotope,stable-isotope,and trace-element analysis in the biological sciences using tandem accelerator mass spectrometry

The new technique of tandem accelerator mass spectrometry (TAMS) has improved the sensitivity for measurement of several long-lived radioisotopes and certain stable isotopes by many orders of magnitude. Nuclear physics tandems and new small dedicated accelerators are now able to measure¹⁴C,¹⁰Be,²⁶Al,³²Si,³⁶Cl,⁴¹Ca, and¹²⁹I in natural materials. Sensitivities down to 10⁵ atoms per sample can be achieved in favorable cases. By accelerating ions to MeV energies, one can eliminate molecules and uniquely identify the atomic numbers below 20. Although most applications to date have been in the earth sciences, the opportunity now exists for important new applications in biology and toxicology. Trace elements can be measured at the parts per billion (10⁹) level using a secondary ion mass spectrometry (SIMS) ion source. Radioactive tracer measurements can be made for elements, such as aluminum, for which there are no isotopes with suitable half-lives for conventional decay counting methods. For¹⁴C, counting times become much shorter and dose levels can be reduced.     

Automation of Mode Locking in a Nonlinear Polarization Rotation Fiber Laser through Output Polarization Measurements

When a laser is mode-locked, it emits a train of ultra-short pulses at a repetition rate determined by the laser cavity length. This article outlines a new and inexpensive procedure to force mode locking in a pre-adjusted nonlinear polarization rotation fiber laser. This procedure is based on the detection of a sudden change in the output polarization state when mode locking occurs. This change is used to command the alignment of the intra-cavity polarization controller in order to find mode-locking conditions. More specifically, the value of the first Stokes parameter varies when the angle of the polarization controller is swept and, moreover, it undergoes an abrupt variation when the laser enters the mode-locked state. Monitoring this abrupt variation provides a practical easy-to-detect signal that can be used to command the alignment of the polarization controller and drive the laser towards mode locking. This monitoring is achieved by feeding a small portion of the signal to a polarization analyzer measuring the first Stokes parameter. A sudden change in the read out of this parameter from the analyzer will occur when the laser enters the mode-locked state. At this moment, the required angle of the polarization controller is kept fixed. The alignment is completed. This procedure provides an alternate way to existing automating procedures that use equipment such as an optical spectrum analyzer, an RF spectrum analyzer, a photodiode connected to an electronic pulse-counter or a nonlinear detecting scheme based on two-photon absorption or second harmonic generation. It is suitable for lasers mode locked by nonlinear polarization rotation. It is relatively easy to implement, it requires inexpensive means, especially at a wavelength of 1550 nm, and it lowers the production and operation costs incurred in comparison to the above-mentioned techniques.     

Coupled external cavity photonic crystal enhanced fluorescence

We report a fundamentally new approach to enhance fluorescence in which surface adsorbed fluorophore‐tagged biomolecules are excited on a photonic crystal surface that functions as a narrow bandwidth and tunable mirror of an external cavity laser. This scheme leads to ～10× increase in the electromagnetic enhancement factor compared to ordinary photonic crystal enhanced fluorescence. In our experiments, the cavity automatically tunes its lasing wavelength to the resonance wavelength of the photonic crystal, ensuring optimal on‐resonance coupling even in the presence of variable device parameters and variations in the density of surface‐adsorbed capture molecules. We achieve ～10⁵× improvement in the limit of detection of a fluorophore‐tagged protein compared to its detection on an unpatterned glass substrate. The enhanced fluorescence signal and easy optical alignment make cavity‐coupled photonic crystals a viable approach for further reducing detection limits of optically‐excited light emitters that are used in biological assays. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Accelerated inactivation of M13 bacteriophage using millijoule femtosecond lasers

Irradiation of femtosecond (fs) pulse lasers in the visible and near‐infrared ranges have been proposed as a promising approach for inactivating viruses. However, in order to achieve significant virus inactivation, past works have required relatively long irradiation times (1 hour or longer), even for small volumes. Given its advantages compared with other techniques, there is an urgent need to shorten the time required to inactivate viruses using fs laser technology. In this study, we investigate the inactivation of purified M13 bacteriophage in phosphate‐buffered saline with large active volume (1 cm³), and short exposure time (several minutes), using lasers with 20 mJ/pulse energy at various wavelengths (800, 400 nm or both 800 and 400 nm combined). For an exposure time of 15 and 2 minute, the use of a 400 nm wavelength laser results in a high load reduction of 5.8 ± 0.3 and 2.9 ± 0.15, respectively, on the log₁₀ scale of viability. We show that virus inactivation using the 400 nm laser is much more efficient compared with that using an 800 nm laser, or the simultaneous irradiation of 400 and 800 nm lasers. Higher pathogen inactivation is observed for lasers with shorter pulse duration, whereas at longer pulse durations, the inactivation is reduced. For millijoule‐energy fs laser irradiation, the M13 bacteriophage inactivation, via the reduction of the functionality of M13 bacteriophages, is accompanied with relatively small amounts of genetic damage.     

31P NMR study of head group behavior in sonicated phosphatidylcholine liposomes in the gel and in the liquid state

We measured the ³¹P[¹H] Nuclear Overhauser Effect (NOE) as a function of temperature and of ¹H irradiation frequency, the linewidth $\text{Δν}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ as a function of temperature and the relaxation time T₁ above and below the thermal transition temperature, of the ³¹P-NMR signal in sonicated liposomes of 1,2-dimiristoyl-3-sn-phosphatidylcholine (DMPC), 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC) and 1,2-dimiristoyl-3-sn-phosphatidylcholine (DSPC). The same measurements were repeated in the presence of high molecular weight dextrans. They strongly reduce the NOE and produce longer relaxation times T₁. According to the current models, we were able to evaluate, in the different situations, the correlation time of the internal motion τ_G and the distance r between interacting groups in the region of the polar head groups. While the first parameter changes abruptly through the phase transition and under the effect of dextrans, the latter does not appear modified in any case. These results are discussed in terms of a conformational change of the phosphocholine head groups.     

Study of the glow dynamics in a laser-produced plasma jet expanding across the magnetic field

Results are presented from experimental studies of the glow dynamics of a plasma jet generated during the irradiation of a plane aluminum target by an iodine laser pulse with the wavelength 1.315 μm. The laser pulse energy was 330–480 J, the pulse duration was 0.5 ns, and the focal spot diameter was 3 mm, the laser intensity on the target surface being ∼10¹³ W/cm². The jet expanded across an external magnetic field with the strength ∼1 kOe. The residual air pressure in the vacuum chamber was ∼10⁻⁵ Torr. The spatiotemporal behavior of the jet glow was investigated using a nine-frame camera in two mutually perpendicular directions (along and across the magnetic field). The results of measurements indicate azimuthal asymmetry of the jet expansion.     

Studies on serum groups in the Kumaon region,India

Summary A total of 469 individuals belonging to 4 endogamous groups (Brahamins, Rajputs, Doms and Tharus) from the Kumaon region (North India) were tested for Hp, Gc, Gm and Inv systems.The frequency of the Hp¹ allele is low (0.130–0.220) in all 4 groups as in the case of other Indian populations. The absence of the Gm⁵ allele and high frequency of Inv(1) (49.34%) confirm the Mongoloid affiliations of the Tharus. Brahamins, Rajputs and Doms possess 4 alleles (Gm¹, Gm^1,2, Gm^1,5 and Gm⁵) at the Gm locus and the frequency of Gm^1,2 allele is very low (0.067–0.106) for these groups. The frequency of Inv(1) for Brahamins (19.61%) and Doms (22.78%) lies within the range of variation of European populations. Rajputs, however, show a higher Inv(1) frequency (38.76%).Genetic distances calculated with the help of Hp, Gc and Gm systems demonstrate similarity between Brahamins, Rajputs and Doms and a deviant position for the Tharus.Supported by the Deutsche Forschungsgemeinschaft.     

Effects of salts on internal DNA pressure and mechanical properties of phage capsids

Based on atomic force microscopy nanoindentation measurements of phage λ, we previously proposed a minimal model describing the effect of water hydrating DNA that strengthens viral capsids against external deformation at wild-type DNA packing density. Here, we report proof of this model by testing the prediction that DNA hydration forces can be dramatically decreased by addition of multivalent ions (Mg²⁺ and Sp⁴⁺). These results are explained using a DNA hydration model without adjustable parameters. The model also predicts the stiffness of other DNA-filled capsids, which we confirm using bacteriophage ?29 and herpes simplex virus type 1 particles.     

A Method to Fabricate Disconnected Silver Nanostructures in 3D

The standard nanofabrication toolkit includes techniques primarily aimed at creating 2D patterns in dielectric media. Creating metal patterns on a submicron scale requires a combination of nanofabrication tools and several material processing steps. For example, steps to create planar metal structures using ultraviolet photolithography and electron-beam lithography can include sample exposure, sample development, metal deposition, and metal liftoff. To create 3D metal structures, the sequence is repeated multiple times. The complexity and difficulty of stacking and aligning multiple layers limits practical implementations of 3D metal structuring using standard nanofabrication tools. Femtosecond-laser direct-writing has emerged as a pre-eminent technique for 3D nanofabrication.^1,2 Femtosecond lasers are frequently used to create 3D patterns in polymers and glasses.^3-7 However, 3D metal direct-writing remains a challenge. Here, we describe a method to fabricate silver nanostructures embedded inside a polymer matrix using a femtosecond laser centered at 800 nm. The method enables the fabrication of patterns not feasible using other techniques, such as 3D arrays of disconnected silver voxels.⁸ Disconnected 3D metal patterns are useful for metamaterials where unit cells are not in contact with each other,⁹ such as coupled metal dot^10,11or coupled metal rod^12,13 resonators. Potential applications include negative index metamaterials, invisibility cloaks, and perfect lenses.In femtosecond-laser direct-writing, the laser wavelength is chosen such that photons are not linearly absorbed in the target medium. When the laser pulse duration is compressed to the femtosecond time scale and the radiation is tightly focused inside the target, the extremely high intensity induces nonlinear absorption. Multiple photons are absorbed simultaneously to cause electronic transitions that lead to material modification within the focused region. Using this approach, one can form structures in the bulk of a material rather than on its surface.Most work on 3D direct metal writing has focused on creating self-supported metal structures.^14-16 The method described here yields sub-micrometer silver structures that do not need to be self-supported because they are embedded inside a matrix. A doped polymer matrix is prepared using a mixture of silver nitrate (AgNO₃), polyvinylpyrrolidone (PVP) and water (H₂O). Samples are then patterned by irradiation with an 11-MHz femtosecond laser producing 50-fs pulses. During irradiation, photoreduction of silver ions is induced through nonlinear absorption, creating an aggregate of silver nanoparticles in the focal region. Using this approach we create silver patterns embedded in a doped PVP matrix. Adding 3D translation of the sample extends the patterning to three dimensions.