The margination and adhesion of micro-particles (MPs) have been extensively investigated separately, due to their important applications in the biomedical field. However, the cascade process from margination to adhesion should play an important role in the transport of MPs in blood flow. To the best of our knowledge, this has not been explored in the past. Here we numerically study the margination behaviour of elastic MPs to blood vessel walls under the interplay of their deformability and adhesion to the vessel wall. We use the lattice Boltzmann method and molecular dynamics to solve the fluid dynamics and particle dynamics (including red blood cells (RBCs) and elastic MPs) in blood flow, respectively. Additionally, a stochastic ligand–receptor binding model is employed to capture the adhesion behaviours of elastic MPs on the vessel wall. Margination probability is used to quantify the localization of elastic MPs at the wall. Two dimensionless numbers are considered to govern the whole process: the capillary number $Ca$ , denoting the ratio of viscous force of fluid flow to elastic interfacial force of MP, and the adhesion number $Ad$ , representing the ratio of adhesion strength to viscous force of fluid flow. We systematically vary them numerically and a margination probability contour is obtained. We find that there exist two optimal regimes favouring high margination probability on the plane $Ca{-}Ad$ . The first regime, namely region I, is that with high adhesion strength and moderate particle stiffness; the other one, region II, has moderate adhesion strength and large particle stiffness. We conclude that the existence of optimal regimes is governed by the interplay of particle deformability and adhesion strength. The corresponding underlying mechanism is also discussed in detail. There are three major factors that contribute to the localization of MPs: (i) near-wall hydrodynamic collision between RBCs and MPs; (ii) deformation-induced migration due to the presence of the wall; and (iii) adhesive interaction between MPs and the wall. Mechanisms (i) and (iii) promote margination, while (ii) hampers margination. These three factors perform different roles and compete against each other when MPs are located in different regions of the flow channel, i.e. near-wall region. In optimal region I, adhesion outperforms deformation-induced migration; and in region II, the deformation-induced migration is small compared to the coupling of near-wall hydrodynamic collision and adhesion. The finding of optimal regimes can help the understanding of localization of elastic MPs at the wall under the adhesion effect in blood flow. More importantly, our results suggest that softer MP or stronger adhesion is not always the best choice for the localization of MPs.
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Confinement effects on DNA hybridization in electrokinetic micro‐ and nanofluidic systems
Spatial confinement, within cells or micro‐ and nanofabricated devices, impacts the conformation and binding kinetics of biomolecules. Understanding the role of spatial confinement on molecular behavior is important for comprehending diverse biological phenomena, as well as for designing biosensors. Specifically, the behavior of molecular binding under an applied electric field is of importance in the development of electrokinetic biosensors. Here, we investigate whether confinement of DNA oligomers in capillary electrophoresis impacts the binding kinetics of the DNA. To infer the role of confinement on hybridization dynamics, we perform capillary electrophoresis measurements on DNA oligomers within micro‐ and nanochannels, then apply first‐order reaction dynamics theory to extract kinetic parameters from electropherogram data. We find that the apparent dissociation constants at the nanoscale (i.e., within a 100 nm channel) are lower than at the microscale (i.e., within a 1 μm channel), indicating stronger binding with increased confinement. This confirms, for the first time, that confinement‐based enhancement of DNA hybridization persists under application of an electric field.
more » « less- NSF-PAR ID:
- 10462140
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ELECTROPHORESIS
- Volume:
- 40
- Issue:
- 5
- ISSN:
- 0173-0835
- Page Range / eLocation ID:
- p. 792-798
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Sample injection in microchip‐based capillary zone electrophoresis (CZE) frequently rely on the use of electric fields which can introduce differences in the injected volume for the various analytes depending on their electrophoretic mobilities and molecular diffusivities. While such injection biases may be minimized by employing hydrodynamic flows during the injection process, this approach typically requires excellent dynamic control over the pressure gradients applied within a microfluidic network. The current article describes a microchip device that offers this needed control by generating pressure gradients on‐chip via electrokinetic means to minimize the dead volume in the system. In order to realize the desired pressure‐generation capability, an electric field was applied across two channel segments of different depths to produce a mismatch in the electroosmotic flow rate at their junction. The resulting pressure‐driven flow was then utilized to introduce sample zones into a CZE channel with minimal injection bias. The reported injection strategy allowed the introduction of narrow sample plugs with spatial standard deviations down to about 45 μm. This injection technique was later integrated to a capillary zone electrophoresis process for analyzing amino acid samples yielding separation resolutions of about 4–6 for the analyte peaks in a 3 cm long analysis channel.
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The spatial arrangement of target and probe molecules on the biosensor is a key aspect of the biointerface structure that ultimately determines the properties of interfacial molecular recognition and the performance of the biosensor. However, the spatial patterns of single molecules on practical biosensors have been unknown, making it difficult to rationally engineer biosensors. Here, we have used high-resolution atomic force microscopy to map closely spaced individual probes as well as discrete hybridization events on a functioning electrochemical DNA sensor surface. We also applied spatial statistical methods to characterize the spatial patterns at the single molecule level. We observed the emergence of heterogeneous spatiotemporal patterns of surface hybridization of hairpin probes. The clustering of target capture suggests that hybridization may be enhanced by proximity of probes and targets that are about 10 nm away. The unexpected enhancement was rationalized by the complex interplay between the nanoscale spatial organization of probe molecules, the conformational changes of the probe molecules, and target binding. Such molecular level knowledge may allow one to tailor the spatial patterns of the biosensor surfaces to improve the sensitivity and reproducibility.more » « less
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This article highlights the role of spatial confinement in controlling the fundamental behavior of molecules. Select examples illustrate the value of using space as a tool to control and understand excited state dynamics through a combination of ultrafast spectroscopy and conventional steady state methods. Molecules of interest were confined within a closed molecular capsule, derived from a cavitand known as octa acid (OA), whose internal void space is sufficient to accommodate molecules as long as tetracene and as wide as pyrene. The free space, i.e. the space that is left following the occupation of the guest within the host, is shown to play a significant role in altering the behavior of guest molecules in the excited state. The results reported here suggest that in addition to weak interactions that are commonly emphasized in supramolecular chemistry, the extent of empty space (i.e. the remaining void space within the capsule) is important in controlling the excited state behavior of confined molecules on ultrafast time scales. For example, the role of free space in controlling the excited state dynamics of guest molecules is highlighted by probing the cis-trans isomerization of stilbenes and azobenzenes within the OA capsule. Isomerization of both types of molecule are slowed when they are confined within a small space, with encapsulated azobenzenes taking a different reaction pathway compared to that in solution upon excitation to S¬2. In addition to steric constraints, confinement of reactive molecules in a small space helps to override the need for diffusion to bring the reactants together, thus enabling the measurement of processes that occur faster than the time scale for diffusion. The advantages of reducing free space and confining reactive molecules are illustrated by recording unprecedented excimer emission from anthracene and by measuring ultrafast electron transfer rates across the organic molecular wall. By monitoring the translational motion of anthracene pairs in a restricted space it has been possible to document the pathway undertaken by excited anthracene from inception to the formation of the excimer on the excited state surface. Similarly, ultrafast electron transfer experiments pursued here have established that the process is not hindered by a molecular wall. Apparently, the electron can cross the OA capsule wall provided the donor and acceptor are in close proximity. Measurements on the ultrafast time scale provide crucial insights for each of the examples presented here, emphasizing the value of both ‘space’ and ‘time’ in controlling and understanding the dynamics of excited molecules.more » « less
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