Dielectric laser acceleration of sub-100 keV electrons with silicon dual-pillar grating structures.

We present the demonstration of high-gradient laser acceleration and deflection of electrons with silicon dual-pillar grating structures using both evanescent inverse Smith-Purcell modes and coupled modes. Our devices accelerate subrelativistic 86.5 and 96.3 keV electrons by 2.05 keV over 5.6 µm distance for accelerating gradients of 370 MeV/m with a 3 nJ mode-locked Ti:sapphire laser. We also show that dual pillars can produce uniform accelerating gradients with a coupled-mode field profile. These results represent a significant step toward making practical dielectric laser accelerators for ultrafast, medical, and high-energy applications.

High-density waveguide superlattices with low crosstalk.

Silicon photonics holds great promise for low-cost large-scale photonic integration. In its future development, integration density will play an ever-increasing role in a way similar to that witnessed in integrated circuits. Waveguides are perhaps the most ubiquitous component in silicon photonics. As such, the density of waveguide elements is expected to have a crucial influence on the integration density of a silicon photonic chip. A solution to high-density waveguide integration with minimal impact on other performance metrics such as crosstalk remains a vital issue in many applications. Here, we propose a waveguide superlattice and demonstrate advanced superlattice design concepts such as interlacing-recombination that enable high-density waveguide integration at a half-wavelength pitch with low crosstalk. Such waveguide superlattices can potentially lead to significant reduction in on-chip estate for waveguide elements and salient enhancement of performance for important applications, opening up possibilities for half-wavelength-pitch optical-phased arrays and ultra-dense space-division multiplexing.

Nanoimprint lithography 20 years on.

To celebrate the 20th anniversary of nanoimprint lithography (NIL) we present a perspective of how the technique and its prospects have evolved over the past two decades. We describe how it overcame certain fabrication challenges at the time it was first reported and look at some of the obstacles that hindered uptake in industry initially, as well as likely sectors for future successful commercial deployment. Developments in the technique since that are making NIL increasingly attractive such as 'moving roll to roll' for higher throughput, are also described.

Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines.

BACKGROUND: To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. CONCLUSIONS/SIGNIFICANCE: For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery.

Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device.

The enumeration of rare circulating epithelial cells (CEpCs) in the peripheral blood of metastatic cancer patients has shown promise for improved cancer prognosis. Moving beyond enumeration, molecular analysis of CEpCs may provide candidate surrogate endpoints to diagnose, treat, and monitor malignancy directly from the blood samples. Thorough molecular analysis of CEpCs requires the development of new sample preparation methods that yield easily accessible and purified CEpCs for downstream biochemical assays. Here, we describe a new immunomagnetic cell separator, the MagSweeper, which gently enriches target cells and eliminates cells that are not bound to magnetic particles. The isolated cells are easily accessible and can be extracted individually based on their physical characteristics to deplete any cells nonspecifically bound to beads. We have shown that our device can process 9 mL of blood per hour and captures >50% of CEpCs as measured in spiking experiments. We have shown that the separation process does not perturb the gene expression of rare cells. To determine the efficiency of our platform in isolating CEpCs from patients, we have isolated CEpCs from all 47 tubes of 9-mL blood samples collected from 17 women with metastatic breast cancer. In contrast, we could not find any circulating epithelial cells in samples from 5 healthy donors. The isolated CEpCs are all stored individually for further molecular analysis.

Structural optimization for heat detection of DNA thermosequencing platform using finite element analysis.

For the past three decades, Sanger's method has been the primary DNA sequencing technology; however, inherent limitations in cost and complexity have limited its usage in personalized medicine and ecological studies. A new technology called "thermosequencing" can potentially reduce both the cost and complexity of DNA sequencing by using a microfluidic platform [Esfandyarpour, Pease, and Davis, J. Vac. Sci. Technol. B26, 661 (2008)]. To optimize the efficiency of the technology, finite element analysis was used to model the thermosequencing system by simulating the DNA incorporation reaction series and the resulting product concentration and heat production. Different models of the thermosequencing platform were created to simulate the effects of the materials surrounding the system, to optimize the geometry of the system, and to concentrate reaction heat into specific regions for detection in the real system. The resulting concentrations of reaction products were used to calibrate the reaction speed and to design the heat sensors in the thermosequencing technology. We recommend a modified gated structure for the microfluidic detection platform by using control valves and show how this new platform could dramatically improve the detection efficiency.