基于碳纳米管X射线源的生物医学成像

Although discovered more than 100 years ago, X-ray source technology has evolved rather slowly. The recent invention of the carbon nanotube (CNT) X-ray source technology holds great promise to revolutionize the field of biomedical X-ray imaging. CNT X-ray sources have been successfully adapted to several biomedical imaging applications including dynamic micro-CT of small animals and stationary breast tomosynthesis of breast cancers. Yet their more important biomedical imaging applications still lie ahead in the future, with the development of stationary multi-source CT as a noteworthy example.     

BIOLUMINESCENCE TOMOGRAPHY： BIOMEDICAL BACKGROUND,MATHEMATICAL THEORY,AND NUMERICAL APPROXIMATION

Over the last couple of years molecular imaging has been rapidly developed to study physiological and pathological processes in vivo at the cellular and molecular levels. Among molecular imaging modalities, optical imaging stands out for its unique advantages, especially performance and cost-effectiveness. Bioluminescence tomography （BLT） is an emerging optical imaging mode with promising biomedical advantages. In this survey paper, we explain the biomedical significance of BLT, summarize theoretical results on the analysis and numerical solution of a diffusion based BLT model, and comment on a few extensions for the study of BLT.     

Contactless dielectrophoretic spectroscopy: examination of the dielectric properties of cells found in blood

The use of non-invasive methods to detect and enrich circulating tumor cells (CTCs) independent of their genotype is critical for early diagnostic and treatment purposes. The key to using CTCs as predictive clinical biomarkers is their separation and enrichment. This work presents the use of a contactless dielectrophoresis (cDEP) device to investigate the frequency response of cells and calculate their area-specific membrane capacitance. This is the first demonstration of a cDEP device which is capable of operating between 10 and 100 kHz. Positive and negative dielectrophoretic responses were observed in red blood cells, macrophages, breast cancer, and leukemia cells. The area-specific membrane capacitances of MDA-MB231, THP-1 and PC1 cells were determined to be 0.01518 ± 0.0013, 0.01719 ± 0.0020, 0.01275 ± 0.0018 (F/m(2)), respectively. By first establishing the dielectrophoretic responses of cancerous cells within this cDEP device, conditions to detect and enrich tumor cells from mixtures with non-transformed cells can be determined providing further information to develop methods to isolate these rare cells.     

Selective concentration of human cancer cells using contactless dielectrophoresis

This work is the first to demonstrate the ability of contactless dielectrophoresis (cDEP) to isolate target cell species from a heterogeneous sample of live cells. Since all cell types have a unique molecular composition, it is expected that their dielectrophoretic (DEP) properties are also unique. cDEP is a technique developed to improve upon traditional and insulator-based DEP devices by replacing embedded metal electrodes with fluid electrode channels positioned alongside desired trapping locations. Through the placement of the fluid electrode channels and the removal of contact between the electrodes and the sample fluid, cDEP mitigates issues associated with sample/electrode contact. MCF10A, MCF7, and MDA-MB-231 human breast cells were used to represent early, intermediate, and late-staged breast cancer, respectively. Trapping frequency responses of each cell type were distinct, with the largest difference between the cells found at 20 and 30 V. MDA-MB-231 cells were successfully isolated from a population containing MCF10A and MCF7 cells at 30 V and 164 kHz. The ability to selectively concentrate cells is the key to development of biological applications using DEP. The isolation of these cells could provide a workbench for clinicians to detect transformed cells at their earliest stage, screen drug therapies prior to patient treatment, increasing the probability of success, and eliminate unsuccessful treatment options.     

Biomedical X-ray Imaging Enabled by Carbon Nanotube X-ray Sources?

Although discovered more than 100 years ago, X-ray source technology has evolved rather slowly. The recent invention of the carbon nanotube (CNT) X-ray source technology holds great promise to revolutionize the field of biomedical X-ray imaging. CNT X-ray sources have been successfully adapted to several biomedical imaging applications including dynamic micro-CT of small animals and stationary breast tomosynthesis of breast cancers. Yet their more important biomedical imaging applications still lie ahead in the future, with the development of stationary multi-source CT as a noteworthy example.     

Performance impact of dynamic surface coatings on polymeric insulator-based dielectrophoretic particle separators

Efficient and robust particle separation and enrichment techniques are critical for a diverse range of lab-on-a-chip analytical devices including pathogen detection, sample preparation, high-throughput particle sorting, and biomedical diagnostics. Previously, using insulator-based dielectrophoresis (iDEP) in microfluidic glass devices, we demonstrated simultaneous particle separation and concentration of various biological organisms, polymer microbeads, and viruses. As an alternative to glass, we evaluate the performance of similar iDEP structures produced in polymer-based microfluidic devices. There are numerous processing and operational advantages that motivate our transition to polymers such as the availability of numerous innate chemical compositions for tailoring performance, mechanical robustness, economy of scale, and ease of thermoforming and mass manufacturing. The polymer chips we have evaluated are fabricated through an injection molding process of the commercially available cyclic olefin copolymer Zeonor 1060R. This publication is the first to demonstrate insulator-based dielectrophoretic biological particle differentiation in a polymeric device injection molded from a silicon master. The results demonstrate that the polymer devices achieve the same performance metrics as glass devices. We also demonstrate an effective means of enhancing performance of these microsystems in terms of system power demand through the use of a dynamic surface coating. We demonstrate that the commercially available nonionic block copolymer surfactant, Pluronic F127, has a strong interaction with the cyclic olefin copolymer at very low concentrations, positively impacting performance by decreasing the electric field necessary to achieve particle trapping by an order of magnitude. The presence of this dynamic surface coating, therefore, lowers the power required to operate such devices and minimizes Joule heating. The results of this study demonstrate that iDEP polymeric microfluidic devices with surfactant coatings provide an affordable engineering strategy for selective particle enrichment and sorting. Figure Model generated image (COMSOL) depicting the electric field gradient divided by the electric field that occurs within an array of insulating posts     

multilayer contactless dielectrophoresis: theoretical considerations

Dielectrophoresis (DEP), the movement of dielectric particles in a nonuniform electric field, is of particular interest due to its ability to manipulate particles based on their unique electrical properties. Contactless DEP (cDEP) is an extension of traditional and insulator-based DEP topologies. The devices consist of a sample channel and fluid electrode channels filled with a highly conductive media. A thin insulating membrane between the sample channel and the fluid electrode channels serves to isolate the sample from direct contact with metal electrodes. Here we investigate, for the first time, the properties of multilayer devices in which the sample and electrode channels occupy distinct layers. Simulations are conducted using commercially available finite element software and a less computationally demanding numerical approximation is presented and validated. We show that devices can be created that achieve a similar level of electrical performance to other cDEP devices presented in the literature while increasing fluid throughput. We conclude, based on these models, that the ultimate limiting factors in device performance resides in breakdown voltage of the barrier material and the ability to generate high-voltage, high-frequency signals. Finally, we demonstrate trapping of MDA-MB-231 breast cancer cells in a prototype device at a flow rate of 1.0 mL/h when 250 V(RMS) at 600 kHz is applied.     

Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature

In this study, the dielectrophoretic response of prostate tumor initiating cells (TICs) was investigated in a microfluidic system utilizing contactless dielectrophoresis (cDEP). The dielectrophoretic response of prostate TICs was observed to be distinctively different than that for non-TICs, enabling them to be sorted using cDEP. Culturing the sorted TICs generated spheroids, indicating that they were indeed initiating cells. This study presents the first marker-free TIC separation from non-TICs utilizing their electrical fingerprints through dielectrophoresis.