Development of silicon interposer: towards an ultralow radioactivity background photodetector system

It is of great importance to develop a photodetector system with an ultralow radioactivity background in rare event searches. Silicon photomultipliers (SiPMs) and application-specific integrated circuits (ASICs) are two ideal candidates for low background photosensors and readout electronics, respectively, because they are mainly composed of silicon, which can achieve good radio-purity without considerable extra effort. However, interposers, used to provide mechanical support and signal routes between the photosensor and the electronics, are a bottleneck in building ultralow background photodetectors. Silicon and quartz are two candidates to construct the low background interposer because of their good radio-purity; nevertheless, it is non-trivial to produce through silicon vias (TSV) or through quartz vias (TQV) on the large area silicon or quartz wafer. In this work, based on double-sided TSV interconnect technology, we developed the first prototype of a silicon interposer with a size of 10~cm$\times$10~cm and a thickness of 320~$\mu$m. The electrical properties of the interposer are carefully evaluated at room temperature, and its performance is also examined at -110~$^\circ$C with an integrated SiPM on the interposer. The testing results reveal quite promising performance of the prototype, and the single photoelectron signals can be clearly observed from the SiPM. The features of the observed signals are comparable with those from the SiPM mounted on a normal FR4-based PCB. Based on the success of the silicon interposer prototype, we started the follow-up studies that aimed to further improve the performance and yield of the silicon interposer, and eventually to provide a solution for building an ultralow background photodetector system

High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients.

(1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short. (2) Methods: We applied an inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs/CTC clusters from patients with metastatic non-small-cell lung cancer (NSCLC). (3) Results: Using Labyrinth, CTCs (PanCK+/DAPI+/CD45-) were isolated from patients (n = 25). Heterogeneous CTC populations, including CTCs expressing epithelial (EpCAM), mesenchymal (Vimentin) or both markers were detected. CTCs were isolated from 100% of patients (417 +/- 1023 CTCs/mL). EpCAM- CTCs were significantly greater than EpCAM+ CTCs. Cell clusters of \u3e/=2 CTCs were observed in 96% of patients-of which, 75% were EpCAM-. CTCs revealed identical genetic aberrations as the primary tumor for RET, ROS1, and ALK genes using fluorescence in situ hybridization (FISH) analysis. (4) Conclusions: The Labyrinth device recovered heterogeneous CTCs in 100% and CTC clusters in 96% of patients with metastatic NSCLC. The majority of recovered CTCs/clusters were EpCAM-, suggesting that these would have been missed using traditional antibody-based capture methods

Inertial focusing of cancer cell lines in curvilinear microchannels

Circulating tumor cells (CTCs) are rare cancer cells, which originate from the primary tumors and migrate to the bloodstream. Separation of CTCs from blood is critical because metastatic CTCs might hold different genomic and phenotypic properties compared to primary tumor cells. In this regard, accurate prognosis and effective treatment methods are necessary. For this purpose, focusing biological particles and cells using microfluidic systems have been implemented as an efficient CTCs enumeration and enrichment method. Passive, continuous, label-free and parallelizable size-dependent focusing based on hydrodynamic forces is preferred in this study to sort cancer cells while avoiding cell death and achieving high throughput. The focusing behavior of MDA-MB-231 (11–22 μm), Jurkat (8–17 μm), K562 (8–22 μm), and HeLa (16–29 μm) was examined with respect to different Reynolds numbers and Dean numbers. The effect of curvature on cell focusing was carefully assessed. The focusing positions of the cells clearly indicated that isolations of MDA cells from MDA-Jurkat cell mixtures as well as of HeLa cells from HeLa-Jurkat cell mixtures were possible by using the curvilinear channels with a curvature angle of 280° at the Reynolds number of 121. © 2019 The Author(s

Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78–83%), high retention of cell viability (71–74%), high tumour cell enrichment against leukocytes (1.7–2 × 10^3), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4–0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research

Ca isotope constraints on chemical weathering processes: evidence from headwater in the Changjiang River, China

This study aims to clarify the relationship between chemical weathering of rocks and the carbon budget of rivers and better understand the weathering mechanisms of plateau watersheds. We chose to study the Jinsha River, which originates from the Tibetan Plateau and also is in the upper reaches of the Changjiang River. Analysis of hydrochemistry, radiogenic strontium isotope and stable calcium isotopes were conducted of the Jinsha River water samples, which were collected along its mainstream and main tributaries in the summer. The results show that the water chemistry of the mainstream waters is dominated by evaporite weathering, which have low 87Sr/86Sr values (0.7098–0.7108) and wide range of Sr contents (2.70–9.35 μmol/L). In contrast, tributaries of the Jinsha River have higher 87Sr/86Sr (0.7090–0.7157) and lower Sr contents (∼1 μmol/L). Moreover, the Ca isotopic compositions in the mainstream (0.87–1.11‰) are heavier than the tributaries (0.68–0.88‰) and could not be fully explained by the conventional mixing of different sources. We suggest that secondary carbonate precipitation fractionates Ca isotopes in the Jinsha River, and fractionation factors are between 0.99935 and 0.99963. At least 66% of Ca was removed in the mainstream of the Jinsha River through secondary mineral precipitation, and the average value is ∼35% in the tributaries. The results highlight that evaporite weathering results in more carbonate precipitation influencing Ca transportation and cycling in the riverine system constrained by stable Ca isotopic compositions and water chemistry

Data for: Quantifying Ca exchange in gypsum using a 45Ca tracer: Implications for interpreting Ca isotopic effects in experimental and natural systems

exchange rate data used in Fig 5. All other raw data are presented in table 1