Tom Tat Luan An Ta Preconcentration Of Charged Species Utilizing Ion Concentration Polarization In Microchannels.pdf

At the inlet of the channel, the bulk flow must surpass the electrophoretic flow to drag biomolecules toward the ion-selective membrane, but it must also ensure that biomolecules cannot

MINISTRY OF EDUCATION AND TRAINING

HANOI UNIVERSITY OF SCIENCE AND TECHNOLOGY

DANG VAN TRUONG

PRECONCENTRATION OF CHARGED SPECIES UTILIZING ION CONCENTRATION POLARIZATION

IN MICROCHANNELS

Specialization in: Mechanics

Code: 9440109

ABSTRACT OF A THESIS SUBMITTED

FOR THE DEGREE OF DOCTOR OF PHILOSOPHY

IN MECHANICS

Hanoi – 2024

The thesis was completed at:

Hanoi University of Science and Technology

Supervisor: ASSOC.PROF PHAM VAN SANG

The dissertation is available at:

1 Ta Quang Buu Library – Hanoi University of Science and Technology

2 Vietnam National Library

Chapter 1 Introduction 1.1 Overview

Micro total analysis systems (TAS) or lab-on-a-chip (LOC) are new microfluidic technologies that have the potential

to revolutionize chemical and biological analyses µTAS can carry out an entire protocol traditionally performed in a laboratory Critical processes, including sample pretreatment, sample transport, mixing, reaction, separation, detection, and product collection, can all be executed simultaneously on a single microchip

Conversely, TAS typically suffers from low analysis sensitivity due to the low detection limits inherent in microchannels The low detection sensitivity is due to the extremely small amounts of dilute analytes and the extremely short optical detection path lengths In chemical or biochemical analyses, such as detecting drug molecules in biological fluids, the drug and its metabolites are typically at much lower concentrations than those prepared in a laboratory Also, the portable analysis equipment used in water analysis is not sensitive enough to investigate the dilute concentrations of organic and inorganic substances in the samples Therefore, miniaturized medical and biomedical analysis systems are promising tools for rapid clinical and forensic diagnostics, but they also necessitate the development of detection and sensing techniques to meet sensitivity and reliability requirements As a result, improving sample concentration is the first critical step in

mechanisms involved These groups are the stacking method, the field gradient focusing, and other special methods grouped into the last one, including electrokinetic trapping, dielectrophoretic trapping, immunocapture-based trapping, magnetic beads-assisted trapping, and thermophoretic trapping

1.3 Foundations of preconcentration by ion concentration polarization (ICP)

Among these focusing methods above, the EKT based on ion concentration polarization (ICP) phenomenon has attracted great attention from the microfluidic research community because it gives the highest CEF and can be applied to almost all biomolecules of interest regardless of their size

Figure 1.1 Schematic of ICP and sample preconcentration in the channel integrated with the ion-selective membrane

In Fig 1.1, the microfluidic concentrator consists of two buffer channels and one sample channel connected by nanochannels to create the ICP phenomenon When applying electric potentials on two electrodes at the end of the sample channel while all electrodes of the buffer channel are connected

to the ground, two separate electric fields are generated,

including the normal field in the nanofluidic channel (E y) and the

tangential field in the microfluidic sample channel (E x) Due to the extremely small size of the nanochannel, an overlapping of the electric double layer is formed, and the nanochannel becomes

the ion-selective membrane Under the application of E y, the counter-ions go through the nanochannel while the co-ions are repelled by the electrostatic repulsion of the channel This biased transport flux between counter-ions and co-ions creates ICP, including an ion depletion zone (IDZ) at the front of the nanochannel in the sample channel and an ion enrichment zone (IEZ) behind the nanochannel in the buffer channels

The microchannels are often charged structures, which, in turn, also intrigue the formation of an electric double layer (EDL)

near the channel walls Under the application of E x, this EDL creates a flow that drives counter-ion, co-ion, and biomolecules called electroosmosis flow or bulk flow from the high-voltage side to the low-voltage side in the sample channel Concurrently, the electrophoresis forces (EP) drive charged biomolecules (often negative) in the opposite direction of the bulk flow As a result, these two flows applied to biomolecules decide the mechanism of sample preconcentration At the inlet of the channel, the bulk flow must surpass the electrophoretic flow to drag biomolecules toward the ion-selective membrane, but it must also ensure that biomolecules cannot be leaked through IDZ toward the channel outlet When these velocities get balanced at

a specific region, biomolecules are trapped at the narrow region called a preconcentration plug, and it is always located at the front of the ion-selective membrane in the sample channel

1.4 Scope and outline of thesis

1.4.1 Scope of thesis

By conducting numerical simulation for the whole problem and solving analytically for the corresponding simplified 2D model, the results obtained in this present study may provide a clearer picture of the separation, preconcentration, and purification of charged species near the ion-selective membrane The results can be used to verify the preconcentration

of charged species and fill the gaps left by previous numerical and experimental studies about forming the separation and preconcentration of charged species in microchannels utilizing the ICP phenomenon near the ion-selective membrane

1.4.2 Outline of the thesis

In Chapter 2, a mathematical model of the physical

transport processes in electrochemical systems was presented

In Chapter 3, the author studied the preconcentration of biomolecules in single microfluidic channels The author examined the formation of the ion depletion zone (IDZ) and ion concentration polarization (ICP) near the ion-selective membrane

In Chapter 4, the author determined the critical dimensions

of microchannels to ensure the preconcentration of biomolecules

By introducing the corresponding simplified 2D model, the author analytically provided solutions for important parameters, including critical dimensions of channels, the position of the preconcentrated biomolecule plug, and the CEF of biomolecules

In Chapter 5, the author studied the preconcentration of biomolecules in convergent microchannels The nozzle-like-squeeze effect of the convergent sector in the channel was examined systematically

Finally, in Chapter 6, the author concluded with remarks

on the preconcentration of charged species near the ion-selective membrane and provided recommendations for future work

Chapter 2 Mathematical models and Numerical

methods 2.1 Introduction

The author developed a general mathematical model for the electrochemical transport of ions and charged species in electrolytes In addition, the author developed numerical methods to solve the Poisson-Nernst-Planck-Navier-Stokes equations To discretize these equations, the author used the finite volume method Furthermore, the author created an OpenFOAM-integrated solver to model the transport of charged species in an electrolyte solution

 = − 

  (2.2)The Poisson's equation for the electric potential distribution in a dielectric material,

2

0

i i e

  = − −   +  −  

2.2.2 Boundary conditions

To close the coupled governing equations above, appropriate boundary conditions representing the physics at the boundaries are required In this section, we define the boundary conditions based on the real physical properties of the boundaries, which describe the actual model conditions

At the left boundary,

2.3 Numerical methods

2.3.1 Overview of numerical methods

There are a number of powerful methods to solve PDEs developed over the last century, but the popular ones are the finite difference method, finite element method, and finite volume method

2.3.2 Finite volume method

The FVM applies the conservation laws that underpin the governing PDEs to the control volumes that comprise the overall computational domain In FVM, the large single control volume

is discretized into a set of smaller control volumes, and the same conservation laws are applied to all of the smaller control volumes, resulting in a set of coupled algebraic equations that can

be conveniently solved on a computer

The author developed numerical methods to solve the Poisson-Nernst-Planck-Navier-Stokes equations The methods can solve complex geometry meshes that can be two or three-dimensional

2.4 Conclusions

The author presented a detailed mathematical model for electrokinetic flow in this chapter In addition, we developed numerical methods to solve the Poisson-Nernst-Planck-Navier-Stokes equations The finite volume method is used to discretize the equations because it is a local conservative method with a low computational cost and applies to complex geometry domains The author also developed the solver based on the OpenFOAM platform to utilize its advantages

Chapter 3 Preconcentration of biomolecules in single

microfluidic channels 3.1 Introduction

Figure 3.1 Schematic illustration of three single-channel designs with a single membrane (or dual membranes) located

in the center of the channel

In this work, the author developed 2-D numerical models for three single-channel designs (SCD), as shown in Fig 3.1 The

first design is the traditional SCD in which a single membrane is patterned at the middle of the channel with one high-voltage electrode at the inlet and one grounded electrode at the outlet of the channel (indicated as SM1G channel) The second design is the enhanced concentration SCD with an additional grounded electrode connected to the membrane (indicated as SM2G channel) The third design is the symmetric SCD with two additional grounded electrodes placed over dual membranes (indicated as DM3G channel)

3.2 Problem statement

All simulation models are 200 μm long and 6 μm high with

a 20 μm long ion selective membrane located at the center of the channel The membrane thickness in Figs 3.3a and 3.3b are 2

μm, while the one in Fig 3.3c has a thickness of 1 μm

3.2.1 The formation of ICP and IDZ

In the SM2G channel and DM3G channel, the ion concentrations are nearly zero at the furthest region from the membrane (where the IDZ is weakest), but in the traditional SM1G channel, the corresponding value is 0.29 mM It is obvious that the two innovative designs significantly generate much stronger IDZ than the one in the traditional design

3.2.2 Effect of electric potential on biomolecule preconcentration

Figure 3.5 also clearly shows that under the same working

conditions, the electric field component E x in the SM2G channel and DM3G channel is much stronger than the one in the

traditional SM1G channel (1.7E 0 and 1.5E 0 compared to 0.4E 0, respectively) Therefore, introducing an additional electrode at the membrane could significantly improve the biomolecule preconcentration rate

a) b)

Figure 3.2 The voltage profile along the channel (y = 3 µm)

in three designs and Case 1

3.2.3 Effect of membrane dimensions and buffer strength on biomolecule preconcentration

Although the amplification of the electric field near the IDZ decreases in both designs, the absolute electric field in the SM2G channel is strong enough to trap biomolecules at the front of the IDZ In contrast, the significant reduction of the electric field in traditional SM1G will cause the leakage of biomolecules through the IDZ and decrease the concentration enhancement effect of the channel

3.2.4 Effect of channel dimensions on biomolecule preconcentration

With the fabrication of a symmetrical membrane of the

DM3G channel, the magnitude of its E x is stronger than the one

in the SM1G channel and SM2G channel, preventing the

protrusion of biomolecules to the outlet side of the membrane, which, in turn, increases the preconcentration rate

times-Chapter 4 Determination of critical dimensions of microchannels for biomolecule preconcentration 4.1 Introduction

In this work, the author reported for the first time the analytical formulas for the critical dimensions of microchannels These formulas were verified with numerical simulation results, and then the possibility of using such analytical formulas to find preliminarily the critical dimensions of microchannels was recommended In addition, the author gave the formula for detecting the location of the preconcentrated biomolecule region This allows manufacturers to determine where to place the biosensors in the microchannel beforehand Moreover, the author provided analytical formulas of important working parameters, including external potentials and critical pressures, to ensure that the area of preconcentrated biomolecules is located at the proper position in the microchannel

4.2 Problem statement

The ion-selective membrane is located in the middle of the sample channel to create the ICP phenomenon under the

application of external potentials V H = 30V 0 and V L = 15V 0 The

simulation model has a length of L c = 520 µm and a width of W

= 15 µm with the ion-selective membrane of the size L m = 20 µm embedded on one side of the channel wall and far from the inlet

1 exp

1 exp

eff B

eff

u L L D

4.3.2 Critical widths of microchannels

Figure 4.1c displays the migration of preconcentrated biomolecule plugs toward the channel inlet when the width of channels reduces If the width is smaller than 3 m, the electroosmotic convection cannot outpace the electrophoretic

migration at the channel inlet, making the maximum velocity of

biomolecules negative, and biomolecules cannot enter the channel This magnitude of the channel width determines the minimum dimension of the channel to ensure the preconcentration of biomolecules

4.3.3 Critical hydraulic pressures

In the case of the 2 m-width channel, which is below the minimum value to ensure the preconcentration of biomolecules

as stated above, the minimum pressure of 12p 0 must be set at the channel inlet to make the convective flow greater than the electrophoretic element

In addition to the minimum pressure required to apply at the channel inlet to ensure the mechanism of biomolecule preconcentration, it is mandatory to keep the hydrostatic pressure

in the range that does not surpass the maximum value When the