Electrothermal transport of third-order fluids regulated by peristaltic pumping.

The study of heat and electroosmotic characteristics in the flow of a third-order fluid regulated by peristaltic pumping is examined by using governing equations, i.e., the continuity equation, momentum equation, energy equation, and concentration equation. The wavelength is considered long compared to its height and a low Reynolds number is assumed. The velocity slip condition is employed. Analytical solutions are performed through the perturbation technique. The expressions for the dimensionless velocity components, temperature, concentration, and heat transfer rate are obtained. Pumping features were computed numerically for discussion of results. Trapping and heat transfer coefficient distributions were also studied graphically. The findings of the present study can be applied to design biomicrofluidic devices like tumor-on-a-chip and organ-on-a-chip.

Modulation of electroosmotic flow in capillary electrophoresis by plant polyphenol-inspired gallic acid/polyethyleneimine coatings: Analysis of small molecules.

Plant polyphenols can form functional coatings on various materials through self-polymerization. In this paper, a series of modified capillary columns, which possess diversity of charge characteristics for modulating electroosmotic flow (EOF), were prepared by one-step co-deposition of gallic acid (GA), a plant-derived polyphenol monomer, and branched polyethyleneimine (PEI). The physicochemical properties of the prepared columns were characterized by Fourier transform infrared spectroscopy (FT-IR), UV-Vis spectroscopy and scanning electron microscopy (SEM). The magnitude and direction of EOF of GA/PEI co-deposited columns were modulated by changing a series of coating parameters, such as post-incubation of FeCl3, co-deposition time, and deposited amounts of GA and PEI with different relative molecular mass (PEI-600, PEI-1800, PEI-10000, and PEI-70000). Furthermore, the separation efficiencies of the prepared GA/PEI co-deposited columns were evaluated by separations of small molecules, including organic acids, polar nucleotides, phenols, nucleic acid bases and nucleosides. Results indicated that modulating of EOF plays an important role in enhancing the separation performance and reversing the elution order of the analytes. Finally, the developed method was successfully applied to quantitative analysis of acidic compounds in four real samples. The recoveries were in the range of 73.5%-85.8% for citric acid, benzoic acid, sorbic acid, salicylic acid and ascorbic acid in beverage and fruit samples, 101.6%-104.9% for cinnamic acid, vanillic acid, and ferulic acid in Angelica sinensis sample, while 84.6%-97.8% for guanosine-5'-monophosphate, uridine-5'-monophosphate, cytosine-5'- monophosphate and adenosine-5'-monophosphate in Cordyceps samples. These results indicated that the co-deposition of plant polyphenol-inspired GA/PEI coatings can provide new opportunities for EOF modulation of capillary electrophoresis.

Electroosmotic flow of non-Newtonian fluids in a constriction microchannel.

Insulator-based dielectrophoresis has to date been almost entirely restricted to Newtonian fluids despite the fact that many of the chemical and biological fluids exhibit non-Newtonian characteristics. We present herein an experimental study of the fluid rheological effects on the electroosmotic flow of four types of polymer solutions, i.e., 2000 ppm xanthan gum (XG), 5% polyvinylpyrrolidone (PVP), 3000 ppm polyethylene oxide (PEO), and 200 ppm polyacrylamide (PAA) solutions, through a constriction microchannel under DC electric fields of up to 400 V/cm. We find using particle streakline imaging that the fluid elasticity does not change significantly the electroosmotic flow pattern of weakly shear-thinning PVP and PEO solutions from that of a Newtonian solution. In contrast, the fluid shear-thinning causes multiple pairs of flow circulations in the weakly elastic XG solution, leading to a central jet with a significantly enhanced speed from before to after the channel constriction. These flow vortices are, however, suppressed in the strongly viscoelastic and shear-thinning PAA solution.

Tunable Electroosmosis-Based Femto-Liter Pipette: A Promising Tool toward Living-Cell Surgery.

Single-cell analysis has attracted increasing attention because of cell heterogeneities. Various strategies have been developed for analyzing single cells, but most of these analytical processes kill the cells. Tools that can qualitatively and quantitatively measure the cellular contents without killing the cell are highly demanding because they enable us to conduct single-cell time-course studies (e.g., to examine how a cell responds to a therapy before, during, and after a treatment). Here we develop a femto-liter (fL) pipet to serve this purpose. To ensure that we can accurately and precisely pipet fL solutions, we fill all conduits with liquid and use an electroosmotic pump (EOP) as the driving force to facilitate withdrawal of cellular contents from single cells. We tentatively term this device an EOP-driven pipette or EDP. We characterize the EDP for accurately and precisely withdrawing solution from ∼250 fL to 80 nL; a volume range that covers the applications for most types of cells. To demonstrate the feasibility of utilizing the EDP for a single-cell time-course study, we utilize the EDP to take the cellular contents out at different times during the course of a zebrafish embryo development for cholesterol measurements. More than 50% of the embryos survive after each pipetting and analysis step, and this number will increase considerably as we improve our cell manipulation skills and reduce the pipet-tip diameter. We expect this EDP to become an effective tool for single-cell time-course studies.

Sequence-Specific Detection of MicroRNAs Related to Clear Cell Renal Cell Carcinoma at fM Concentration by an Electroosmotically Driven Nanopore-Based Device.

MicroRNAs (miRs) are small noncoding RNAs that play a critical role in gene regulation. Recently, traces of cancer-related miRs have been identified in body fluids, which make them remarkable noninvasive biomarkers. In this study, a new nanopore-based detection scheme utilizing a borosilicate micropipette and an assay of complementary γ-peptide nucleic acid (γ-PNA) probes conjugated to polystyrene beads have been reported for the detection of miR-204 and miR-210 related to the clear cell Renal Cell Carcinoma (ccRCC). Electroosmotic flow (EOF) is induced as the driving force to transport PNA-beads harboring target miRs to the tip of the pore (sensing zone), which results in pore blockades with unique and easily distinguishable serrated shape electrical signals. The concentration detection limit is investigated to be 1 and 10 fM for miR-204 and miR-210, respectively. The EOF transport mechanism enables highly sensitive detection of molecules with low surface charge density with 97.6% detection accuracy compared to the conventional electrophoretically driven methods. Furthermore, resistive-pulse experiments are conducted to study the correlation of the particles' surface charge density with their translocation time and verify the detection principle.

Regulating the Membrane Transport Activity and Death of Cells via Electroosmotic Manipulation.

Although the volume of living cells has been known to heavily influence their behavior and fate, a method allowing us to control the cell size in a programmable manner is still lacking. Here, we develop a technique in which precise changes in the cellular volume can be conveniently introduced by varying the voltage applied across a Nafion membrane that separates the culture medium from a reservoir. It is found that, unlike sudden osmotic shocks, active ion transport across the membrane of leukemia K562 cells will not be triggered by a gradual change in the extracellular osmolarity. Furthermore, when subjected to the same applied voltage, different lung and nasopharyngeal epithelial cancer cells will undergo larger volumetric changes and have a 5-10% higher death rate compared to their normal counterparts. We show that such distinct response is largely caused by the overexpression of aquaporin-4 in tumor cells, with knockout of this water channel protein resulting in a markedly reduced change in the cellular volume. Finally, by taking into account the exchange of water/ion molecules across the Nafion film and the cell membrane, a theoretical model is also proposed to describe the voltage-induced size changes of cells, which explain our experimental observations very well.

Combining selection valve and mixing chamber for nanoflow gradient generation: Toward developing a liquid chromatography cartridge coupled with mass spectrometer for protein and peptide analysis.

Toward developing a micro HPLC cartridge, we have recently built a high-pressure electroosmotic pump (EOP). However, we do not recommend people to use this pump to deliver an organic solvent directly, because it often makes the pump rate unstable. We have experimented several approaches to address this issue, but none of them are satisfactory. Here, we develop an innovative approach to address this issue. We first create an abruption (a dead-volume) within a fluid conduit. We then utilize an EOP to withdraw, via a selection valve, a train of eluent solutions having decreasing eluting power into the fluid conduit. When these solutions are further aspirated through the dead-volume, these solutions are partially mixed, smoothening concentration transitions between two adjacent eluent solutions. As these solutions are pushed back, through the dead-volume again, a smooth gradient profile is formed. In this work, we characterize this scheme for gradient formation, and we incorporate this approach with a high-pressure EOP, a nanoliter injection valve, and a capillary column, yielding a micro HPLC system. We then couple this micro HPLC with an electrospray ionization - mass spectrometer for peptide and protein separations and identifications.

Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures.

This review covers recent advances in sampling fluid from the extracellular space of brain tissue by electroosmosis (EO). Two techniques, EO sampling with a single fused-silica capillary and EO push-pull perfusion, have been developed. These tools were used to investigate the function of membrane-bound enzymes with outward-facing active sites, or ectoenzymes, in modulating the activity of the neuropeptides leu-enkephalin and galanin in organotypic-hippocampal-slice cultures (OHSCs). In addition, the approach was used to determine the endogenous concentration of a thiol, cysteamine, in OHSCs. We have also investigated the degradation of coenzyme A in the extracellular space. The approach provides information on ectoenzyme activity, including Michaelis constants, in tissue, which, as far as we are aware, has not been done before. On the basis of computational evidence, EO push-pull perfusion can distinguish ectoenzyme activity with a ~100 µm spatial resolution, which is important for studies of enzyme kinetics in adjacent regions of the rat hippocampus.

Stacking open-capillary electroosmotic pumps in series to boost the pumping pressure to drive high-performance liquid chromatographic separations.

Numerous micropumps have been developed, but few of them can produce adequate flow rate and pressure for high-performance liquid chromatography (HPLC) applications. We have recently developed an innovative hybrid electroosmotic pump (EOP) to solve this problem. The basic unit of a hybrid pump consists of a +EOP (the pumping element is positively charged) and a -EOP (the pumping element is negatively charged). The outlet of the +EOP is then joined with the inlet of the -EOP, forming a basic pump unit, while the anode of a positive high voltage (HV) power supply is placed at the joint. The inlet and outlet of this pump unit are electrically grounded. With this configuration, we can stack many of such pump units in series to boost the pumping power. In this work, we describe in details how an open-capillary hybrid EOP is constructed and characterize this pump systematically. We also show that a hybrid EOP with ten serially stacked pump units can deliver a maximum pressure of 21.5 MPa (∼3100 psi). We further demonstrate the feasibility of using this hybrid EOP to drive eluents for HPLC separations of proteins and peptides.

Numerical studies of continuous nutrient delivery for tumour spheroid culture in a microchannel by electrokinetically-induced pressure-driven flow.

Continuous nutrient delivery to cells by pressure-driven flow is desirable for cell culture in lab-on-a-chip devices. An innovative method is proposed to generate an induced pressure-driven flow by using an electrokinetically-driven pump in a H-shape microchannel. A three-dimensional numerical model is developed to study the effectiveness of the proposed mechanism. It is shown that the average velocity of the generated pressure-driven flow is linearly dependent on the applied voltage. Considering the culture of a multicellular tumour spheroid (MTS) in such a microfluidic system, numerical simulations based on EMT6/Ro tumour cells is performed to find the effects of the nutrient distribution (oxygen and glucose), bulk velocity and channel size on the cell growth. Using an empirical formula, the growth of the tumour cell is studied. For low nutrient concentrations and low speed flows, it is found that the MTS grows faster in larger channels. It is also shown that, for low nutrient concentrations, a higher bulk liquid velocity provide better environment for MTS to grow. For lower velocities, it is found that the local MTS growth along the flow direction deviates from the average growth.

Chemical synthesis in microreactors.

To develop a new generation of drugs, pharmaceutical companies need to be able to synthesise and screen novel chemicals with enhanced speed. New technology that would enable a cost neutral step change in the number of potential drug candidates would provide a distinct competitive advantage. Indeed the miniaturisation of chemical reactors offers many fundamental and practical advantages of relevance to the pharmaceutical industry, who are constantly searching for controllable, information-rich, high-throughput, environmentally friendly methods of producing products with a high degree of chemical selectivity. This chapter reviews the current and future applications of microreactors that could enhance the drug discovery process.