Automated, real-time material detection during ultrashort pulsed laser machining using laser-induced breakdown spectroscopy, for process tuning, end-pointing, and segmentation.

The rapid, high-resolution material processing offered by ultrashort pulsed lasers enables a wide range of micro and nanomachining applications in a variety of disciplines. Complex laser processing jobs conducted on composite samples, require an awareness of the material type that is interacting with laser both for adjustment of the lasering process and for endpointing. This calls for real-time detection of the materials. Several methods such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-Ray spectroscopy (EDS) can be used for material characterization. However, these methods often need interruption of the machining process to transfer the sample to another instrument for inspection. Such interruption significantly increases the required time and effort for the machining task, acting as a prohibitive factor for many laser machining applications. Laser induced breakdown spectroscopy (LIBS) is a powerful technique that can be used for material characterization, by analyzing a signal that is generated upon the interaction of laser with matter, and thus, it can be considered as a strong candidate for developing an in-situ characterization method. In this work, we propose a method that uses LIBS in a feedback loop system for real time detection and decision making for adjustment of the lasering process on-the-fly. Further, use of LIBS for automated material segmentation, in the 3D image resulting from consecutive lasering and imaging steps, is showcased.

Terahertz-readable laser engraved marks as a novel solution for product traceability.

Counterfeit products pose significant economic, security, and health risks. One approach to mitigate these risks involves establishing product provenance by tracing them back to their manufacturing origins. However, current identification methods, such as barcodes and RFIDs, have limitations that make them vulnerable to counterfeiting. Similarly, nonvolatile memories, physically unclonable functions, and emerging techniques like Diamond Unclonable Security Tag and DNA fingerprinting also have their own limitations and challenges. For a traceability solution to gain widespread adoption, it must meet certain criteria, including being inexpensive, unique, immutable, easily readable, standardized, and unclonable. In this paper, we propose a solution that utilizes ultrashort pulsed lasers to create unique, unclonable, and immutable physical tags. These tags can then be read nondestructively using far-field Terahertz (THz) spectroscopy. The primary objective of this paper is to investigate the feasibility of our proposed approach. We aim to assess the ability to distinguish laser marks with varying depths, evaluate the sensitivity of THz reading to laser engraving parameters, examine the capacity to capture high-information-density marks, and explore the ability to capture subsurface tags. By addressing these aspects, our method holds the potential to serve as a universal solution for a wide range of traceability applications.

Gas-assisted femtosecond pulsed laser machining: A high-throughput alternative to focused ion beam for creating large, high-resolution cross sections.

Cross sectioning is a critical sample preparation technique used in a wide range of applications, that enables investigation of buried layers and subsurface features or defects. State-of-the-art cross-sectioning methods, each have their own pros and cons, but generally suffer from a tradeoff between throughput and accuracy. Mechanical methods are fast but lack accuracy. On the other hand, ion-based methods, such as focused ion beam (FIB), offer high resolutions but are slow. Lasers, which can potentially improve this tradeoff, face multiple challenges that include creation of heat affected zones (HAZs), undesirably large spot size as well as material redeposition. In this work, we utilized, for the first time, a femtosecond pulsed laser, which has been shown to cause minimal to zero HAZ, for rapid creation of large cross sections that are comparable with FIB cross sections in quality. The laser was integrated with a targeted CO2 gas delivery system for redeposition control and beam tail curtailing, and a hard mask for top surface protection and further shrinkage of the effective spot size. The performance of the proposed system is showcased through real world examples that compare the throughput and quality resulted from the laser and FIB cross sectioning techniques.

Femtosecond laser hierarchical surface restructuring for next generation neural interfacing electrodes and microelectrode arrays.

Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve stimulation, as well as sensing and recording electrical signals to and from neural tissue. To improve specificity, functionality, and performance of these devices, the electrodes and microelectrode arrays-that are the basis of most emerging devices-must be further miniaturized and must possess exceptional electrochemical performance and charge exchange characteristics with neural tissue. In this report, we show for the first time that the electrochemical performance of femtosecond-laser hierarchically-restructured electrodes can be tuned to yield unprecedented performance values that significantly exceed those reported in the literature, e.g. charge storage capacity and specific capacitance were shown to have improved by two orders of magnitude and over 700-fold, respectively, compared to un-restructured electrodes. Additionally, correlation amongst laser parameters, electrochemical performance and surface parameters of the electrodes was established, and while performance metrics exhibit a relatively consistent increasing behavior with laser parameters, surface parameters tend to follow a less predictable trend negating a direct relationship between these surface parameters and performance. To answer the question of what drives such performance and tunability, and whether the widely adopted reasoning of increased surface area and roughening of the electrodes are the key contributors to the observed increase in performance, cross-sectional analysis of the electrodes using focused ion beam shows, for the first time, the existence of subsurface features that may have contributed to the observed electrochemical performance enhancements. This report is the first time that such performance enhancement and tunability are reported for femtosecond-laser hierarchically-restructured electrodes for neural interfacing applications.

Rapid high-resolution volumetric imaging via laser ablation delayering and confocal imaging.

Acquiring detailed 3D images of samples is needed for conducting thorough investigations in a wide range of applications. Doing so using nondestructive methods such as X-ray computed tomography (X-ray CT) has resolution limitations. Destructive methods, which work based on consecutive delayering and imaging of the sample, face a tradeoff between throughput and resolution. Using focused ion beam (FIB) for delayering, although high precision, is low throughput. On the other hand, mechanical methods that can offer fast delayering, are low precision and may put the sample integrity at risk. Herein, we propose to use femtosecond laser ablation as a delayering method in combination with optical and confocal microscopy as the imaging technique for performing rapid 3D imaging. The use of confocal microscopy provides several advantages. First, it eliminates the 3D image distortion resulting from non-flat layers, caused by the difference in laser ablation rate of different materials. It further allows layer height variations to be maintained within a small range. Finally, it enables material characterization based on the processing of material ablation rate at different locations. The proposed method is applied on a printed circuit board (PCB), and the results are validated and compared with the X-ray CT image of the PCB part.

What does COVID-19 testing results really say? The real statistics concealed behind the accessible data.

Accurate and comprehensive testing is crucial for practitioners to portray the pandemic. Without testing there is no data; yet, the exact number of infected people cannot be determined due to the lack of comprehensive testing. The number of seropositive for SARS-CoV-2 infection is obviously relative to the extent of testing. However, the true number of infections might be still far higher than the reported values. To compare the countries based on the number of seropositive for SARS-CoV-2 infection is misleading, as there may not be enough tests being carried out to properly monitor the outbreak. In this paper, we closely look through the COVID-19 testing results. Herein, we try to draw conclusions based on the reported data: first, the presence of a possible relationship between COVID-19 transition and patients' age will be assessed. Then, the COVID-19 case fatality rate (CFR) is compared with the age-demographic data for different countries. Based on the results, a method for estimating a lower bound (minimum) for the number of actual positive cases will be developed and validated. Results of this study have shown that CFR is a metric reflecting the spread of the virus, but is a factor of the extent of testing and does not necessarily show the real size of the outbreak. Moreover, no large difference in susceptibility by age has been found. The results suggest the similarity between the age distribution of COVID-19 and the population age-demographic is improving over the course of the pandemic. In addition, countries with lower CFRs have a more similar COVID-19 age distribution, which is a result of more comprehensive testing. Finally, a method for estimation of the real number of infected people based on the age distributions, reported CFRs, and the extent of testing will be developed and validated.

Approximating net interactions among rigid domains.

Many physical simulations aim at evaluating the net interaction between two rigid bodies, resulting from the cumulative effect of pairwise interactions between their constituents. This is manifested particularly in biomolecular applications such as hierarchical protein folding instances where the interaction between almost rigid domains directly influences the folding pathway, the interaction between macromolecules for drug design purposes, self-assembly of nanoparticles for drug design and drug delivery, and design of smart materials and bio-sensors. In general, the brute force approach requires quadratic (in terms of the number of particles) number of pairwise evaluation operations for any relative pose of the two bodies, unless simplifying assumptions lead to a collapse of the computational complexity. We propose to approximate the pairwise interaction function using a linear predictor function, in which the basis functions have separated forms, i.e. the variables that describe local geometries of the two rigid bodies and the ones that reflect the relative pose between them are split in each basis function. Doing so replaces the quadratic number of interaction evaluations for each relative pose with a one-time quadratic computation of a set of characteristic parameters at a preprocessing step, plus constant number of pose function evaluations at each pose, where this constant is determined by the required accuracy of approximation as well as the efficiency of the used approximation method. We will show that the standard deviation of the error for the net interaction is linearly (in terms of number of particles) proportional to the regression error, if the regression errors are from a normal distribution. Our results show that proper balance of the tradeoff between accuracy and speed-up yields an approximation which is computationally superior to other existing methods while maintaining reasonable precision.

Assemble-And-Match: A Novel Hybrid Tool for Enhancing Education and Research in Rational Structure Based Drug Design.

Rational drug design is the process of finding new medication that can activate or inhibit the biofunction of a target molecule by binding to it and forming a molecular complex. Here, shape and charge complementarities between drug and target are key. To help find effective drug molecules out of a huge pool of possibilities, physical and computer aided tools have been developed. Former offers a tangible experience of the molecular interactions yet lacks measurement and evaluation capabilities. Latter enables accurate and fast evaluations, but does not deliver the interactive tangible experience of physical models. We introduce a novel hybrid model called "Assemble-And-Match" where, we enhance and combine the unique features of the two categories. Assemble-And-Match works based on fabrication of customized molecular fragments using our developed software and a 3D printer. Fragments are hinged to each other in different combinations and form flexible peptide chains, conformable to tertiary structures, to fit in the binding pocket of a (3D printed) target molecule. Through embedded measurement marks, the molecular model is reconstructed in silico and its properties are evaluated. We expect Assemble-And-Match tool can enable combination of visuospatial perception with in silico computational power to aid research and education in drug design.

Tumor Control Index as a new tool to assess tumor growth in experimental animals.

Measurement of tumor diameters, tumor volumes, or area under the curve has been traditionally used to quantitate and compare tumor growth curves in immune competent as well as immune-compromised mice and rats. Here, using tumor growth data from a large number of mice challenged with live tumor cells, we describe the use of a new composite parameter, Tumor Control Index (TCI) as an alternative method to do the same. This index, comprised of three distinct values, the Tumor Inhibition Score, Tumor Rejection Score, and Tumor Stability Score, provides a complete picture of nearly every aspect of tumor growth in large numbers of animals, can be deduced automatically from tumor diameter or volume data, and can be used to compare several groups of animals in different experiments. This automatically derivable index also corresponds neatly to the use of complete and partial responses and tumor stability data generated in human tumors, and can be used to assess the efficacy of interventions to be used in clinical studies.