5. Disease detection

Sections 1–3 have detailed how bioparticles can be characterized, iDEP devices modeled/simulated and how the numerically obtained device architecture can be fabricated using lithography and transferred to polymer using prototyping. This section will focus more on testing the fabricated devices and comparing its efficiency with the numerically obtained one. The experimental process of disease detection using iDEP devices starts with preparation of the bioparticles for DEP experiment. In some cases, the bioparticles of interests are cultured while in other cases, they are obtained and tested directly from donors, stored temporarily and worked on. Several other methods exist for obtaining samples. Irrespective of the method of obtaining the bioparticle samples, one important factor to consider before experimentation is the properties of the suspending medium. It is customary in iDEP experimentations to suspend bioparticles in a medium prior to feeding them into the inlet reservoir. During the operation of the iDEP device, it is necessary to prevent Joule heating or electrolysis in the iDEP devices by using lowconducting medium. Preventing Joule heating circumvents, amongst other things, any form of recirculation within the channel especially at the post-constriction regions [7]. Knowing that cells are cultured in relatively conducting medium at pH range that depends on the nature of the bioparticles, it is necessary to pre-treat the samples and make them fit for dielectrophoretic experimentation. The pH value of the suspending medium affects the Zeta potential of the bioparticle as well as that of the iDEP channel wall. These will in turn affect the electro-osmotic and electrophoretic contributions to the flux of particles within the channel. Apart from the medium pH, its tonicity (which is related to its osmolality) is also important. A hypertonic medium causes plasmolysis while a hypotonic result in cell turgidity. According to Eq. 3, the dielectrophoretic force experience by bioparticles depends, amongst other factors, on the size of the particle. If the suspending medium is hypertonic, it results in an increased particle radius whose effect on the DEP force is to the third power. Reduction in particle radius when the particles are suspended in a hypotonic solution has a reversed effect on the DEP force. For this reason, isotonic solution may be the more appropriate medium for preserving the cell size since there is no net movement of fluid when the cells are suspended. 5% dextrose and 0.9% NaCl are considered isotonic medium and are therefore good choices for iDEP experiments. Using direct current (DC) to generate electric field for iDEP experiment requires that one leverage the membrane characteristics of the bio-particles in context. This is because DC manipulation of cells cares less about the variation in field frequency which is the main factor in AC fields (higher AC frequency tends to put cytoplasmic contributions into account). According to the complex permittivity relation, <sup>~</sup>ε<sup>i</sup> <sup>¼</sup> <sup>ε</sup><sup>i</sup> � <sup>j</sup> <sup>σ</sup><sup>i</sup> <sup>ω</sup>, the first term on the right represents, for a cell membrane, the polarization component of the dielectric (membrane) while the second component represent the dielectric loss component. Since DC and low-frequency AC fields seem to be comparable in terms of their effects on biological cells, it is expected that dielectric loss might be an issue. Primarily, a healthy cell has a membrane that separates its intercellular contents from its outer environment. Situated within the membrane are channels that allow certain ions to be exchanged between the internal and external environment of the cell depending on their concentrations on either side of the membrane. The disparity in the concentration-pair results in

Applications of Electrokinetics and Dielectrophoresis on Designing Chip-Based Disease… DOI: http://dx.doi.org/10.5772/intechopen.82637

membrane potential which is usually maintained as resting membrane potential through ion leakage and pumping. This potential difference places certain capacitance on the membrane relative to the charges associated with both sides of the membrane. At the onset of infection (intracellular infection, for instance), the damage to the membrane causes excessive ion change, which results in a change in the capacitance of the membrane. If the infection had engendered some proteins to be expressed on the cell membrane, that would have disrupted the charge distribution on the external environment contiguous to the membrane resulting in a different membrane capacitance. This difference is enough to make healthy and infected move into different paths when placed in a dielectrophoretic micro channel [18]. When infected and healthy cells move to diverse exit ports, they can be easily quantified and/or qualified. Common qualification technique involves post separation microscopic evaluation. This might involve cell staining and fluorescence characterization. In some cases, post separation qualification is achieved by integrating sensors i.e. measuring impedance or capacitance along the exit channels. These sensors work in a similar fashion to impedance cytometry. When separated a particle passes through the gap between the sensor, spectra are generated from where the nature of the particle is verified and compared with any baseline spectra. For identifying extracellular infection in human blood, for instance, there is a need to primarily isolate the blood plasma and then explore the possibility of singling out the pathogen. Lyme disease is best detected this way, but the process can be very challenging due to the complexity of the plasma component.
