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Abstract Stemming from the high-profile publication of Nissen and Wolski (N Engl J Med 356:2457–2471, 2007) and subsequent discussions with divergent views on how to handle observed zero-total-event studies, defined to be studies that observe zero number of event in both treatment and control arms, the research topic concerning the common odds ratio model with zero-total-event studies remains to be an unresolved problem in meta-analysis. In this article, we address this problem by proposing a novel repro samples method to handle zero-total-event studies and make inference for the common odds ratio. The development explicitly accounts for the sampling scheme that generates the observed data and does not rely on any large sample approximations. It is theoretically justified with a guaranteed finite-sample performance. Simulation studies are designed to demonstrate the empirical performance of the proposed method. It shows that the proposed confidence set, although a little conservative, achieves the desired empirical coverage rate in all situations. The development also shows that the zero-total-event studies contain meaningful information and impact the inference for the common odds ratio. The proposed method is used to perform a meta-analysis of the 48 trials reported in Nissen and Wolski (N Engl J Med 356:2457–2471, 2007) as well 

Polyvinyl chloride (PVC) containing municipal solid waste (MSW) streams are difficult to recycle and mostly landfilled due to various detrimental effects PVC causes to waste recycling. In this work, a single-step upcycling of PVC-containing commingled wastes in tetrahydrofuran was investigated using cellulose, PVC, polyethylene (PE), polypropylene (PP), and polystyrene (PS) to model the wastes. During the co-conversion, in-situ produced HCl derived from PVC decomposition acted as an acid catalyst to selectively decompose cellulose into liquid mainly containing levoglucosan (LGA) and furfural. It was also found that the presence of PE, PP, and PS in the mixture synergistically enhanced the cellulose-derived monomer productions and increased the reaction rate for producing the monomers by suppressing secondary reactions of HCl in the solvent. The maximum LGA yield from co-conversion of cellulose, PVC, and PS was 35.4% after a 5 min reaction compared to the 31.7% obtained without PS in the mixture. In addition to converting cellulose to chemicals, PVC-derived polyaromatics and partly decomposed PE, PP, and PS were recovered as solids. The dechlorinated solids had higher heating values up to 46.11 MJ/kg, achieved by co-converting cellulose, PVC, and PP. When used as oil absorbents in water, the solid recovered from converting cellulose, PVC, and PE mixture showed the highest absorption capability. Overall, the presented approach offers a promising way for upcycling PVC-containing wastes in which PVC properties and its molecular structure are leveraged to enhance the conversion. 

Abstract Circulating tumor cells (CTCs) are shed from primary tumors, circulate in the bloodstream and are capable of initiating metastasis at distant anatomical sites. The detection and molecular characterization of CTCs are pivotal for early-stage cancer diagnosis and prognosis. Recently, microfluidic technology has achieved significant progress in the separation of cells from complex and heterogeneous mixtures for many biomedical applications. Conventional microfluidic platforms exploit the difference in size between the particles to achieve separation, which makes them ineffective for sorting overlapping-sized CTCs. To address this issue, we propose a method using a spiral channel for label-free, and high throughput separation of CTCs coupling Dielectrophoresis (DEP) with inertial microfluidics. A numerical model has been developed to investigate the separation effectiveness of the device over a range of electrical voltage and flow rates. The presented channel is shown to effectively isolate similar-sized CTCs from the white blood cells (WBCs) in a single-stage separation process. Subsequently, optimum working parameters to enhance separation efficiency have been proposed. The hybrid microfluidic device can provide valuable insight into the development of a robust, inexpensive, and efficient platform for cell separation with reduced analysis time for future cancer research and treatment. 

Deterministic lateral displacement (DLD) is a microfluidic method for the continuous separation of particles based on their size. There is growing interest in using DLD for harvesting circulating tumor cells from blood for further assays due to its low cost and robustness. While DLD is a powerful tool and development of high-throughput DLD separation devices holds great promise in cancer diagnostics and therapeutics, much of the experimental data analysis in DLD research still relies on error-prone and time-consuming manual processes. There is a strong need to automate data analysis in microfluidic devices to reduce human errors and the manual processing time. In this work, a reliable particle detection method is developed as the basis for the DLD separation analysis. Python and its available packages are used for machine vision techniques, along with existing identification methods and machine learning models. Three machine learning techniques are implemented and compared in the determination of the DLD separation mode. The program provides a significant reduction in video analysis time in DLD separation, achieving an overall particle detection accuracy of 97.86% with an average computation time of 25.274 s. 

Abstract Isolation and detection of circulating tumor cells (CTCs) hold significant importance for the early diagnosis of cancer and the assessment of therapeutic strategies. However, the scarcity of CTCs among peripheral blood cells presents a major challenge to their detection. Additionally, a similar size range between CTCs and white blood cells (WBCs) makes conventional microfluidic platforms inadequate for the isolation of CTCs. To overcome these challenges, in this study, a novel inertial‐dielectrophoretic microfluidic channel for size‐independent, single‐stage separation of CTCs from WBCs has been presented. The proposed device utilizes a spiral microchannel embedded with interdigitated electrodes. A numerical model is developed and validated to investigate the influence of various parameters related to the channel design, fluid flow, and electrode configuration. It was found that optimal separation of CTCs could be obtained at a relatively low voltage, termed the critical voltage. Furthermore, at the critical voltage of 7.5 V, the hybrid microchannel is demonstrated to be capable of separating CTCs from different WBC subtypes including granulocytes, monocytes, T‐, and B‐lymphocytes. The unique capabilities of the hybrid spiral microchannel allow for this size‐independent isolation of CTCs from a mixture of WBCs. Overall, the proposed technique can be readily utilized for continuous and high‐throughput separation of cancer cells. 

Abstract The efficient isolation of viable and intact circulating tumor cells (CTCs) from blood is critical for the genetic analysis of cancer cells, prediction of cancer progression, development of drugs, and evaluation of therapeutic treatments. While conventional cell separation devices utilize the size difference between CTCs and other blood cells, they fail to separate CTCs from white blood cells (WBCs) due to significant size overlap. To overcome this issue, we present a novel approach that combines curved contraction–expansion (CE) channels with dielectrophoresis (DEP) and inertial microfluidics to isolate CTCs from WBCs regardless of size overlap. This label‐free and continuous separation method utilizes dielectric properties and size variation of cells for the separation of CTCs from WBCs. The results demonstrate that the proposed hybrid microfluidic channel can effectively isolate A549 CTCs from WBCs regardless of their size with a throughput of 300 μL/min, achieving a high separation distance of 233.4 μm at an applied voltage of 50 V_p–p. The proposed method allows for the modification of cell migration characteristics by controlling the number of CE sections of the channel, applied voltage, applied frequency, and flow rate. With its unique features of a single‐stage separation, simple design, and tunability, the proposed method provides a promising alternative to the existing label‐free cell separation techniques and may have a wide range of applications in biomedicine. 

Abstract Circulating Tumor Cells (CTCs), which migrate from original sites in a body to distant organs through blood, are a key factor in cancer detection. Emerging Label-free techniques owing to their inherent advantage to preserve characteristics of sorted cells and low consumption of samples can be promising to the prediction of cancer progression and metastasis research. Deterministic Lateral Displacement (DLD) is one of the label-free separation techniques employing a specific arrangement of micro-posts for continuous separation of suspended cells in a buffer based on the size of cells. Separation based solely on size is challenging since the size distributions of CTCs might overlap with those of normal blood cells. To address this problem, DLD can be combined with dielectrophoresis (DEP) technique which is the phenomenon of particle movement in a non-uniform electric field owing to the polarization effect. Although, DLD devices employ the laminar flow in low Reynolds number (Re) fluid flow due to predictability of such flow regimes, they should be improved to work in higher Re flow regime so as to attain high throughput devices. In this paper, a particle tracing simulation is developed to study the effects of different post shapes, shift fraction of micropost arrays, and dielectrophoresis forces on separation of CTCs from peripheral blood cells. Our numerical model and results provide a groundwork for design and fabrication of high-throughput DLD-DEP devices for improvement of CTC separation.