Lab-on-chip devices are an emerging microsystem technology in which laboratory functions are miniaturized into compact, chip-scale packages. Such devices enable analyses to be performed at lower cost and higher speed than with traditional methods. One major application area for these devices is their use in sorting and separating biological particles.ududIn this dissertation, we present a new technique for separating biological particles on lab-on-chip platforms. The foundation of our method is dielectrophoresis, a technique where AC electric fields are used to manipulate particles in a fluid, based on their inherent electrical properties. These electrical properties reflect differences not just in size, but also capture subtle variations in the internal composition of the particle. Using a novel time-multiplexed combination of dielectrophoresis methods over very dense electrode arrays, we can create strong electric fields with a high degree of spatial resolution. When placed in the presence of these fields, particles with variations in composition can be made to experience different amounts of force, forces in opposite directions, or no force at all simply by applying fields of specific frequency and phase in particular regions of the electrode array. By time-multiplexing, or rapidly alternating the field configuration over time, we can exert differential forces on particles of varying types. Time-multiplexing dielectrophoresis enables separations between particle types to take place under conditions that would otherwise make them inseparable. The application of the method significantly loosens the requirements competing methods have on maintaining a buffer with specific electric properties and has the ability to increase the differential rate at which particles migrate apart. As a result of our method, the use of dielectrophoresis to separate particles becomes a viable alternative in real-world situations.ududTo demonstrate our claims we have created a small library of five particle types, including yeast cells and polystyrene microspheres of varying types. We have selected appropriate electrical models for each of these particles and use the models to analytically validate our methodology. For this dissertation, we have also developed a novel lab-on-chip hardware platform to experimentally validate our models and demonstrate the effectiveness of our technique. The presented methodology and its implementation have the potential to serve as the basis for a new class of point-of-care, portable diagnostic devices by allowing researchers to sort and assay particles of interest based on their structure and composition without the use of expensive and destructive biochemical labeling techniques.ud
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机译:芯片实验室设备是一种新兴的微系统技术,该技术将实验室功能微型化为紧凑的芯片级封装。与传统方法相比,此类设备能够以更低的成本和更高的速度执行分析。这些设备的一个主要应用领域是它们在生物颗粒的分类和分离中的应用。 ud ud在本文中,我们提出了一种在芯片实验室平台上分离生物颗粒的新技术。我们方法的基础是介电泳,该技术基于其固有的电特性,使用交流电场来处理流体中的粒子。这些电学性质不仅反映出大小上的差异,还反映出颗粒内部组成的细微变化。在非常密集的电极阵列上使用介电电泳方法的新型时分多路复用组合,我们可以创建具有高空间分辨率的强电场。当放置在这些电场的存在下时,只需在电极阵列的特定区域中施加特定频率和相位的电场,即可使组成变化的粒子经受不同大小的力,相反方向的力或完全不施加力。通过时分复用或随时间快速改变场配置,我们可以对不同类型的粒子施加不同的力。时分复用介电泳使颗粒类型之间的分离能够在其他条件下不可分离的条件下进行。该方法的应用大大放松了竞争方法对维持具有特定电性能的缓冲液的要求,并具有增加颗粒迁移分开的差异速率的能力。作为我们方法的结果,使用介电电泳分离颗粒在现实世界中成为可行的选择。 ud ud为了证明我们的主张,我们创建了一个包含五种颗粒类型的小型文库,包括酵母细胞和各种不同的聚苯乙烯微球类型。我们为这些微粒中的每一个都选择了合适的电气模型,并使用这些模型来分析验证我们的方法。在本文中,我们还开发了一种新颖的芯片实验室硬件平台,以通过实验验证我们的模型并证明我们技术的有效性。通过允许研究人员根据其结构和组成对感兴趣的颗粒进行分类和测定,而无需使用昂贵的分子筛,所提出的方法及其实施方法有可能成为新型即时护理便携式诊断设备的基础。破坏性的生化标记技术。
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