Temperature Gradient Focusing Research Articles

Temperature gradient focusing of bio-analyte in a microfluidic channel dealing with non-Newtonian electrolyte considering temperature-dependent zeta potential.

Temperature gradient focusing (TGF) relies on establishing a precise balance between the electrophoretic motility of a target analyte and the advective flow of the background electrolyte (BGE) to locally concentrate the analyte in a microfluidic configuration. This paper presents a finite-element-based numerical analysis where the coupled electric field and the transport equations are solved to describe the effects of the shear-dependent apparent viscosity of a non-Newtonian BGE on the localized concentration buildup of a charged bio-sample inside a microchannel by TGF via Joule heating. Effects of the temperature-dependent nature of the wall zeta potential and the flow behavior index (n) of BGE on the flow, thermal, and species concentration profiles inside the microchannel have been investigated. Study using a fluorescein-Na analyte sample shows that the maximum normalized analyte concentration (Cmax /C0 ) reduces as the zeta potential increases linearly with temperature. The maximum concentration enhancement is achieved when the BGE displays the Newtonian rheology. For example, Cmax /C0 increases 134- to 280-fold when n is increased from 0.8 to 1 (pseudoplastic regime) and again reduces to 190-fold when n increases further from 1 to 1.2 (dilatant regime).

Nonlinear Temperature Gradient Focusing of Deoxyribose Nucleic Acid in a Microfluidic Channel With Patterned Surface Charges: A Numerical Study

Abstract We present a numerical analysis of electrophoretic transport of a biological sample, such as, deoxyribose nucleic acid (DNA) via nonlinear temperature gradient within a microfluidic channel having patterned surface charges. The transport of the electrolyte is induced by electroosmotic force by imposing an axial electric field, superposed with the wall electric field via electrodes embedded along the wall of the microchannel. We consider the periodic variation of wall zeta potential in electrokinetic motion of an electrolyte wherein the DNA sample exhibits electrophoretic migration. Temperature dependence of the thermophysical properties of the electrolyte and the electrophoretic mobility and diffusivity of the analyte sample is accounted for in the model to improve its accuracy. Nonlinear longitudinal temperature field along the microchannel is induced via Joule heating by suitably shaping the channel geometry, which enhances the concentration of DNA approximately 270 folds by applying just 500 V DC field with constant zeta potential at the walls. The study further reveals that the concentration of DNA reduces drastically when a periodic wall zeta potential is applied. Results of the study lend to the design of novel electrically actuated bio-microfluidic devices with tunable solute separation and dispersion capabilities.

Microfluidic Concentration Enhancement of Bio-Analyte by Temperature Gradient Focusing via Joule Heating by DC Plus AC Field: A Numerical Approach

Abstract We present a detailed numerical analysis of electrophoresis induced concentration of a bio-analyte facilitated by temperature gradient focusing (TGF) in a phosphate buffer solution via Joule heating inside a converging–diverging microchannel. The purpose is to study the effects of frequency of AC field and channel width variation on the concentration of target analyte. We tune the buffer viscosity, conductivity, and electrophoretic mobility of the analyte such that the electrophoretic velocity of the analyte locally balances the electroosmotic flow (EOF) of the buffer, resulting in a local build-up of the analyte concentration in a target region. An AC field is superimposed on the applied DC field within the microchannel in such a way that the back pressure effect is minimized, resulting in minimum dispersion and high concentration of the target analyte. Axial transport of fluorescein-Na in the phosphate buffer solution is controlled by inducing temperature gradient through Joule heating. The technique leverages the fact that the buffer’s ionic strength and viscosity depend on temperature, which in turn guides the analyte transport. A numerical model is proposed and a finite element-based solution of the coupled electric field, mass, momentum, energy, and species transport equations are carried out. Simulation predict peak of 670-fold concentration of fluorescein-Na is achieved. The peak concentration is found to increase sharply as the channel throat width decreases, while the axial spread of concentrated analyte increases at lower frequency of AC field. The results of the work may improve the design of micro concentrator.

Electrokinetically driven continuous-flow enrichment of colloidal particles by Joule heating induced temperature gradient focusing in a convergent-divergent microfluidic structure

Enrichment of colloidal particles in continuous flow has not only numerous applications but also poses a great challenge in controlling physical forces that are required for achieving particle enrichment. Here, we for the first time experimentally demonstrate the electrokinetically-driven continuous-flow enrichment of colloidal particles with Joule heating induced temperature gradient focusing (TGF) in a microfluidic convergent-divergent structure. We consider four mechanisms of particle transport, i.e., advection due to electroosmosis, electrophoresis, dielectrophoresis and, and further clarify their roles in the particle enrichment. It is experimentally determined and numerically verified that the particle thermophoresis plays dominant roles in enrichment of all particle sizes considered in this study and the combined effect of electroosmosis-induced advection and electrophoresis is mainly to transport particles to the zone of enrichment. Specifically, the enrichment of particles is achieved with combined DC and AC voltages rather than a sole DC or AC voltage. A numerical model is formulated with consideration of the abovementioned four mechanisms, and the model can rationalize the experimental observations. Particularly, our analysis of numerical and experimental results indicates that thermophoresis which is usually an overlooked mechanism of material transport is crucial for the successful electrokinetic enrichment of particles with Joule heating induced TGF.

Development of a fast thermal response microfluidic system using liquid metal

Room temperature liquid metal gallium alloy has been widely used in many micro-electromechanical systems applications, such as on-chip electrical microheaters, micro temperature sensors, micro pumps and so on. Injecting liquid metal into microchannels can provide a simple, rapid, low-cost but efficient way to integrate these elements in microfluidic chips with high accuracy. The liquid metal-filled microstructures can be designed in any shape and easily integrated into microfluidic chips. In this paper, an on-chip liquid metal-based thermal microfluidic system is proposed for quick temperature control at the microscale. The micro system utilizes just one microfluidic chip as a basic working platform, which has liquid metal-based on-chip heaters, temperature sensors and electroosmotic flow pumps. Under the comprehensive control of these elements, the micro system can quickly change the temperature of a target fluid in the microfluidic chip. These liquid metal-based on-chip elements are very helpful for the fabrication and miniaturization of the microfluidic chip. In this paper, deionized water is used to test the temperature control performance of the thermal microfluidic system. According to the experimental results, the micro system can efficiently control the temperature of water ranging from 28 °C to 90 °C. The thermal microfluidic system has great potential for use in many microfluidic applications, such as on-chip polymerase chain reaction, temperature gradient focusing, protein crystallization and chemical synthesis.

Microfluidic two-dimensional separation of proteins combining temperature gradient focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

A two-dimensional separation system is presented combining scanning temperature gradient focusing (TGF) and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) in a PDMS/glass microfluidic chip. Denatured proteins are first focused and separated in a 15 mm long channel via TGF with a temperature range of 16-47 °C and a pressure scanning rate of -0.5 Pa/s and then further separated via SDS-PAGE in a 25 mm long channel. A side channel is designed at the intersection between the two dimensions to continuously inject SDS into the gel, allowing SDS molecules to be compiled within the focused bands. Separation experiments are performed using several fluorescently labeled proteins with single point detection. Experimental results show a dramatic improvement in peak capacity over one-dimensional separation techniques.

Microfluidic concentration of sample solutes using Joule heating effects under a combined AC and DC electric field

This paper reports both experimental and numerical studies of our proposed electrokinetic focusing technique. The technique utilizes a combined AC and DC field for enhancing Joule heating induced temperature gradient focusing (TGF) of sample solutes in a microfluidic device. Our experimental results show that introducing an AC field component can provide sufficient Joule heating to generate temperature gradient required for achieving TGF of sample solutes, while the electroosmotic flow is suppressed under the relatively high frequency of the AC electric field. Consequently, concentration enhancement of sample solutes is considerably increased by using the combined AC and DC electric field technique. A numerical model including a set of multi-physical governing equations is presented to describe the complex TGF of sample solutes under a combined AC and DC field, and a scaling analysis of the time scales of several transport processes is conducted to simplify the numerical model. The numerical predictions are found in reasonable agreement with the measured Joule heating induced temperature profiles and electrokinetic flow field but show less dispersive than the observed focusing band of sample solutes and slightly over-estimate the experimental concentration enhancement. Several factors such as mass dispersion and photobleaching effect can contribute to the discrepancies between the model predictions and the experimental results.

Rapid concentration of deoxyribonucleic acid via Joule heating induced temperature gradient focusing in poly-dimethylsiloxane microfluidic channel

This paper reports rapid microfluidic electrokinetic concentration of deoxyribonucleic acid (DNA) with the Joule heating induced temperature gradient focusing (TGF) by using our proposed combined AC and DC electric field technique. A peak of 480-fold concentration enhancement of DNA sample is achieved within 40s in a simple poly-dimethylsiloxane (PDMS) microfluidic channel of a sudden expansion in cross-section. Compared to a sole DC field, the introduction of an AC field can reduce DC field induced back-pressure and produce sufficient Joule heating effects, resulting in higher concentration enhancement. Within such microfluidic channel structure, negative charged DNA analytes can be concentrated at a location where the DNA electrophoretic motion is balanced with the bulk flow driven by DC electroosmosis under an appropriate temperature gradient field. A numerical model accounting for a combined AC and DC field and back-pressure driven flow effects is developed to describe the complex Joule heating induced TGF processes. The experimental observation of DNA concentration phenomena can be explained by the numerical model.

Numerical study of the effect of microchannel geometry on temperature gradient focusing using the Joule heating effect

We performed a numerical analysis to investigate the effect of microchannel geometry on the temperature gradient focusing (TGF) process using the Joule heating phenomenon. The governing equations were implemented into a quasi-one-dimensional (1-D) numerical model along a microchannel. The distributions of temperature, velocity, and concentration along the microchannel were predicted based on the numerical results. The narrower middle width and wider outside width of a channel with a fixed length improved the focusing performance. However, an excessively narrow middle width of the channel generates an improper high temperature that can cause problems, including sample denaturation and buffer solution boiling. Therefore, the geometry of the microchannel should be optimized to prevent these problems. We propose optimal microchannel widths for TGF using the ratio of the middle width and the outside width of the channel in order to improve focusing performance.

Study of Liquid-Metal Based Heating Method for Temperature Gradient Focusing Purpose

Temperature gradient focusing (TGF) is a highly efficient focusing technique for the concentration and separation of charged analytes in microfluidic channels. The design of an appropriate temperature gradient is very important for the focusing efficiency. In this study, we proposed a new technique to generate the temperature gradient. This technique utilizes a microchannel filled with liquid-metal as an electrical heater in a microfluidic chip. By applying an electric current, the liquid-metal heater generates Joule heat, forming the temperature gradient in the microchannel. To optimize the temperature gradient and find out the optimal design for the TGF chip, numerical simulations on four typical designs were studied. The results showed that design 1 can provide a best focusing method, which has the largest temperature gradient. For this best design, the temperature is almost linearly distributed along the focusing microchannel. The numerical simulations were then validated both theoretically and experimentally. The following experiment and theoretical analysis on the best design also provide a useful guidance for designing and fabricating the liquid-metal based TGF microchip.

A Review of Heating and Temperature Control in Microfluidic Systems: Techniques and Applications.

This review presents an overview of the different techniques developed over the last decade to regulate the temperature within microfluidic systems. A variety of different approaches has been adopted, from external heating sources to Joule heating, microwaves or the use of lasers to cite just a few examples. The scope of the technical solutions developed to date is impressive and encompasses for instance temperature ramp rates ranging from 0.1 to 2,000 °C/s leading to homogeneous temperatures from −3 °C to 120 °C, and constant gradients from 6 to 40 °C/mm with a fair degree of accuracy. We also examine some recent strategies developed for applications such as digital microfluidics, where integration of a heating source to generate a temperature gradient offers control of a key parameter, without necessarily requiring great accuracy. Conversely, Temperature Gradient Focusing requires high accuracy in order to control both the concentration and separation of charged species. In addition, the Polymerase Chain Reaction requires both accuracy (homogeneous temperature) and integration to carry out demanding heating cycles. The spectrum of applications requiring temperature regulation is growing rapidly with increasingly important implications for the physical, chemical and biotechnological sectors, depending on the relevant heating technique.

Micellar affinity gradient focusing in a microfluidic chip with integrated bilinear temperature gradients

Micellar affinity gradient focusing (MAGF) is a microfluidic counterflow gradient focusing technique that combines the favorable features of MEKC and temperature gradient focusing. MAGF separates analytes on the basis of a combination of electrophoretic mobility and partitioning with the micellar phase. A temperature gradient is produced along the separation channel containing an analyte/micellar system to create a gradient in interaction strength (retention factor) between the analytes and micelles. Combined with a bulk counterflow, species concentrate at a unique point where their total velocity sums to zero. MAGF can be used in scanning mode by varying the bulk flow so that a large number of analytes can be sequentially focused and passed by a single detection point. In this work, we develop a bilinear temperature gradient along the separation channel that improves separation performance over the conventional linear designs. The temperature profile along the channel consists of a very sharp gradient used to preconcentrate the sample followed by a shallow gradient that increases resolution. We fabricated a hybrid PDMS/glass microfluidic chip with integrated micro heaters that generate the bilinear profile. Performance is characterized by separating several different samples including fluorescent dyes using SDS surfactant and pI markers using both SDS and poly-SUS surfactants as the micellar phase. The new design shows a nearly two times improvement in peak capacity and resolution in comparison to the standard linear temperature gradient.

Bilinear Temperature Gradient Focusing in a Hybrid PDMS/Glass Microfluidic Chip Integrated with Planar Heaters for Generating Temperature Gradients

Temperature gradient focusing (TGF) is a counterflow gradient focusing technique, which utilizes a temperature gradient across a microchannel or capillary to separate analytes. With an appropriate buffer, the temperature gradient creates a gradient in both the electric field and electrophoretic velocity. Combined with a bulk counter flow, ionic species concentrate at a unique point where the total velocity sums to zero and separate from each other. Scanning TGF uses varying bulk flow so that a large number of analytes that have large differences in electrophoretic mobility can be sequentially focused and passed by a single detection point. Up to now, scanning TGF examples have been performed using a linear temperature gradient which has limitations in improving peak capacity and resolution at the same time. In this work, we develop a bilinear temperature gradient along the separation channel that improves both peak capacity and separation resolution simultaneously. The temperature profile along the channel consists of a very sharp gradient used to preconcentrate the sample followed by a shallow gradient that increases separation resolution. A specialized design is developed for the heaters to achieve the bilinear profile using both analytical and numerical modeling. The heaters are integrated onto a hybrid PDMS/glass chip fabricated using conventional sputtering and soft-lithography techniques. Separation performance is characterized by separating several different dyes and amino acids that have close electrophoretic mobilities. Experiments show a dramatic improvement in peak capacity and resolution in comparison to the standard linear temperature gradient.

Optothermal sample preconcentration and manipulation with temperature gradient focusing

In this article, we present an optothermal analyte preconcentration method based on temperature gradient focusing. This approach offers a flexible, noninvasive technique for focusing and transporting charged analytes in microfluidics using light energy. The method uses the optical field control provided by a digital projector as established for particle manipulation, to achieve analogous functionality for molecular analytes for the first time. The optothermal heating system is characterized and the ability to control of the heated zone location, size, and power is demonstrated. The method is applied to concentrate a sample model analyte, along a microcapillary, resulting in almost 500-fold local concentration increase in 15 min. Optically controlled upstream and downstream transport of a focused analyte band is demonstrated with a heater velocity of ∼170 μm/min.

온도기울기 농축(TGF) 향상을 위한 미세채널 형상 최적화 연구

Temperature gradient focusing (TGF) of analytes via Joule heating is achieved when electric field is applied along a microchannel of varying width. The effect of varying width of the microchannel for the focusing performance of the device was numerically studied. The governing equations were implemented into a quasi-1D numerical model along a microchannel. The validity of the numerical model was verified by a comparison between numerical and experimental results. The distributions of temperature, velocity, and concentration along a microchannel were predicted by the numerical results. The narrower middle width and wider outside width of the channel having the fixed length contribute to improve the focusing performance of the device. However, too narrow middle width of the channel generates a higher temperature which can cause the problems including sample denaturation and buffer solution boiling. Therefore, the channel geometry should be optimized to prevent these problems. The optimal widths of the microchannel for the improvement on TGF were proposed and this model can be easily applied to lab-on-a-chip (LOC) applications where focusing is required based on its simple design.

Towards high concentration enhancement of microfluidic temperature gradient focusing of sample solutes using combined AC and DC field induced Joule heating

It is challenging to continuously concentrate sample solutes in microfluidic channels. We present an improved electrokinetic technique for enhancing microfluidic temperature gradient focusing (TGF) of sample solutes using combined AC and DC field induced Joule heating effects. The introduction of an AC electric field component services dual functions: one is to produce Joule heat for generating temperature gradient; the other is to suppress electroosmotic flow. Consequently the required DC voltages for achieving sample concentration by Joule heating induced TGF are reduced, thereby leading to smaller electroosmotic flow (EOF) and thus backpressure effects. As a demonstration, the proposed technique can lead to concentration enhancement of sample solutes of more than 2500-fold, which is much higher than the existing literature reported microfluidic concentration enhancement by utilizing the Joule heating induced TGF technique.

Concentration enhancement of sample solutes in a sudden expansion microchannel with Joule heating

Microfluidic concentration of sample solutes is achieved by using temperature gradient focusing (TGF) in a microchannel with a step change in cross-section. A mathematical model is developed to describe the complex TGF processes. Scaling analysis is conducted to estimate time scales so as to simplify the proposed mathematical model. Numerical computations are performed to obtain the temperature, velocity and sample concentration distributions which allow us to reveal the insightful TGF mechanisms. Experiments are carried out to study the effects of applied voltage, buffer concentration, and channel size on the TGF of sample solutes in both PSMD/Glass and PDMS/PDMS microdevices. It is found that the focusing location of samples varies with these experimental parameters, and this scenario can be explained using our present numerical model. In addition, the experimental parametric effects are summarized using a dimensionless Joule number that is introduced in this study. The Joule number effect in the PDMS/PDMS microdevice is compared with that in the PDMS/Glass microdevice. A more than 450-fold concentration enhancement is obtained within 75 s in the PDMS/PDMS microdevice. Overall, the numerical simulations are found in reasonable agreement with the experimental results.

Temperature gradient focusing in miniaturized free‐flow electrophoresis devices

Temperature gradient focusing is a method to separate and focus any charged analytes even without accessible isoelectric point, and has been already widely used in CE. In this paper, we demonstrate the application of temperature gradient focusing to free-flow electrophoresis. Besides focusing and separation experiments of proteins, the stability of the temperature gradient under flow conditions and the temperature dependence of fluorescence dyes have also been investigated.

Microsystem for Field-Amplified Electrokinetic Trapping Preconcentration of DNA at Poly(ethylene terephthalate) Membranes

In electrokinetic trapping (EKT), the electroosmotic velocity of a buffer solution in one area of a microfluidic device opposes the electrophoretic velocity of the analyte in a second area, resulting in transport of DNA to a location where the electrophoretic and electroosmotic velocities are equal and opposite and DNA concentrates at charged nanochannels. The method does not require an optical plug localization, a considerable advantage as compared to preconcentration techniques previously presented. In the work reported here, the trapping process is preceded by a field-amplification in the sample reservoir to reduce trapping time, as field-amplified EKT is shown to be an effective technique to preconcentrate samples from larger volumes. A theoretical model explaining the principle of field-amplified EKT considers different ionic strengths and cross-sectional areas in the microchip segments. The model is supported by experimental data using nucleic acids and fluorescein as sample analytes. An incorporated poly(ethylene terephthalate) (PET) membrane provides anion exclusion due to a negatively charged surface. A fluidic counter flow supports the trapping process in 100 nm pores due to anion exclusion. An analysis of Joule heating gives evidence that temperature gradient focusing effects are negligible and charge exclusion is responsible for trapping. The theoretical model developed and experimentally demonstrated can be exploited for the preconcentration of cell free fetal DNA circulating in maternal plasma and other rare nucleic acid species present in large sample volumes.

Bioanalytical separations using electric field gradient techniques

The field of separations science will be strongly impacted by new electric-field-gradient-based strategies. Many new capabilities are being developed with analytical targets ranging from particles to small molecules, and soot to living cells. Here we review the emerging area of electric field gradient techniques, dividing the large variety of techniques by the target of separation. In doing so, we have contributions using dielectrophoresis, electric field gradient focusing (including dynamic, true moving bed, and pulsed field), electrocapture and electrophoretic focusing, temperature gradient focusing, and focusing with centrifugal force. We cover the literature from the start of 2007 to June 2008, along with some introductory discussions. Even with the relatively short time frame, this young and dynamic field of inquiry produced some 100 contributions describing new and unique techniques and several new applications.