Targeting Magnetic Nanoparticles in Physiologically Mimicking Tissue Microenvironment.

Magnetic nanoparticles as drug carriers, despite showing immense promises in preclinical trials, have remained to be only of limited use in real therapeutic practice primarily due to unresolved anomalies concerning their grossly contrasting controllability and variability in performance in artificial test benches as compared to human tissues. To circumvent the deficits of reported in vitro drug testing platforms that deviate significantly from the physiological features of the living systems and result in this puzzling contrast, here, we fabricate a biomimetic microvasculature in a flexible tissue phantom and demonstrate distinctive mechanisms of magnetic-field-assisted controllable penetration of biocompatible iron oxide nanoparticles across the same, exclusively modulated by tissue deformability, which has by far remained unraveled. Our experiments deciphering the transport of magnetic nanoparticles in a blood analogue medium unveil a decisive interplay of the flexibility of the microvascular pathways, magnetic pull, and viscous friction toward orchestrating the optimal vascular penetration and targeting efficacy of the nanoparticles in colorectal tissue-mimicking bioengineered media. Subsequent studies with biological cells confirm the viability of using localized magnetic forces for aiding nanoparticle penetration within cancerous lesions. We establish nontrivially favorable conditions to induce a threshold force for vascular rupture and eventual target of the nanoparticles toward the desired extracellular site. These findings appear to be critical in converging the success of in vitro trials toward patient-specific targeted therapies depending on personalized vascular properties obtained from medical imaging data.

Microparticle Suspensions and Bacteria-Laden Droplets: Are They the Same in Terms of Wetting Signature?

Adhesion behavior of microbial pathogens on commonly encountered surfaces is one of the most pertinent questions now. We present the characterization of bacteria-laden droplets and quantify the adhesion forces on highly repellent surfaces with the help of a simple experimental setup. Comparing the force signature measured directly using an in-house capillary deflection-based droplet force apparatus, we report an anomalous adhesion behavior of live bacteria (E. coli)-laden droplets on repellent surfaces, which stands in stark contrast to the observed adhesion signature when the doping agent is changed to inert microparticles or the same bacteria in an incapacitated state. We showed that the regular contact angle measurements using optical goniometry is unable to differentiate between the live bacteria and the dead ones (including microparticles) and thus delineate its limitations and the complementary nature of the adhesion measurements in understanding the fundamental interfacial interaction of living organisms on solid surfaces.

Friction and Adhesion of Microparticle Suspensions on Repellent Surfaces.

With the recent advancements in the development and application of repellent surfaces, both in air and under liquid medium, accurate characterization of repellence behavior is critical in understanding the mechanism behind many observed phenomena and to exploit them for novel applications. Conventionally, the repellence behavior of a surface is characterized by the optical measurement of the dynamic contact angle of the target (to be repelled) liquid on the test surface. However, as already established in the literature, optical measurements are prone to appreciable error, especially for repellent surfaces with high contact angles. Here, we present an alternative, more accurate force-based characterization method of both friction and adhesion forces of microparticle-laden aqueous droplets over various repellent surfaces, where the force signature is captured by probing the surface with a droplet of the test liquid mounted at the tip of a flexible cantilever and then tracking the deflection of the tip of the cantilever as the probe droplet interacts with the surface. A systematic investigation of the response of repellent surfaces toward droplets with different microparticle concentrations reveals the dependency and sensitivity of measured adhesion and friction signature toward particle concentration. A comparison with the theoretical estimate from optical goniometry highlights the deviation of the theoretical data from experimentally measured values and further substantiates the need for such a force-based approach for accurate characterization of repellence behavior.

Biomimetic pulsatile flows through flexible microfluidic conduits.

We bring out unique aspects of the pulsatile flow of a blood analog fluid (Xanthan gum solution) in a biomimetic microfluidic channel. Pressure waveforms that mimic biologically consistent pulsations are applied on physiologically relevant cylindrical microchannels fabricated using polydimethylsiloxane. The in vivo features of the relevant waveforms like peak amplitude and dicrotic notch are reproduced in vitro. The deformation profiles exhibit viscoelastic behavior toward the end of each cycle. Further, the time-varying velocity profiles are critically analyzed. The local hydrodynamics within the microchannel is found to be more significantly affected by pressure waveform rather than the actual wall deformation and the velocity profile. These results are likely to bear far-reaching implications for assessing micro-circulatory dynamics in lab on a chip based microfluidic platforms that to a large extent replicate physiologically relevant conditions.

Collective dynamics of red blood cells on an in vitro microfluidic platform.

Understanding the dynamics of blood flow in physiologically relevant confinements turns out to be an outstanding proposition in biomedical research. Despite the large number of studies being reported to theoretically elucidate the dynamics of red blood cells (RBCs) in confined geometries, in vitro experimental studies unveiling the implications of the collective dynamics of red blood cells in physiologically relevant bio-mimetic microfluidic channels remain elusive. Here, we investigate the implications of complex dynamvic interactions between the whole blood and a deformable channel wall fabricated using a hydrogel matrix. For a range of flow rates, we map the trajectories of the RBCs for varying levels of softness of the microchannel wall. We compare these scenarios with the reference cases of rigid polydimethylsiloxane (PDMS) channels. Our results reveal that the smallest channels investigated herein exhibit the most intricate interactions between the collective dynamics of the RBC and the wall flexibility, attributable to confinement-induced hydrodynamic interactions in the presence of spatially varying shear rates. These results may open up new paradigms in conceptual understanding of in vivo dynamics of blood flow through simple in vitro experiments on a simple microfluidic platform.