Leidong Mao

High Density Orthogonal Surface Immobilization via Photoactivated Copper-Free Click Chemistry

Surfaces containing reactive ester polymer brushes were functionalized with cyclopropenone-masked dibenzocyclooctynes for the light activated immobilization of azides using catalyst-free click chemistry. The photodecarbonylation reaction in the amorphous brush layer is first order for the first 45 s with a rate constant of 0.022 s(-1). The catalyst-free cycloaddition of surface bound dibeznocyclooctynes proceeds rapidly in the presence of azides under ambient conditions. Photolithography using a shadow mask was used to demonstrate patterning with multiple azide containing molecules. This surface immobilization strategy provides a general and facile platform for the generation of multicomponent surfaces with spatially resolved chemical functionality.

Magnetic Nanoparticle-Based Hyperthermia for Head & Neck Cancer in Mouse Models

In this study, magnetic iron oxide nanoparticle induced hyperthermia is applied for treatment of head and neck cancer using a mouse xenograft model of human head and neck cancer (Tu212 cell line). A hyperthermia system for heating iron oxide nanoparticles was developed by using alternating magnetic fields. Both theoretical simulation and experimental studies were performed to verify the thermotherapy effect. Experimental results showed that the temperature of the tumor center has dramatically elevated from around the room temperature to about 40oC within the first 5-10 minutes. Pathological studies demonstrate epithelial tumor cell destruction associated with the hyperthermia treatment.

Acceleration of Tissue Plasminogen Activator-Mediated Thrombolysis by Magnetically Powered Nanomotors

Dose control and effectiveness promotion of tissue plasminogen activator (t-PA) for thrombolysis are vitally important to alleviate serious side effects such as hemorrhage in stroke treatments. In order to increase the effectiveness and reduce the risk of stroke treatment, we use rotating magnetic nanomotors to enhance the mass transport of t-PA molecules at the blood clot interface for local ischemic stroke therapy. The in vitro experiments demonstrate that, when combined with magnetically activated nanomotors, the thrombolysis speed of low-concentration t-PA (50 μg mL–1) can be enhanced up to 2-fold, to the maximum lysis speed at high t-PA concentration. Based on the convection enhanced transport theory due to rotating magnetic nanomotors, a theoretical model is proposed and predicts the experimental results reasonably well. The validity and efficiency of this enhanced treatment has been demonstrated in a rat embolic model.

Overcoming the Diffusion Barrier: Ultra-Fast Micro-Scale Mixing Via Ferrofluids

We report on the design, development, fabrication and characterization of a novel, micro-scale mixing device based on stable water suspensions of magnetic nanoparticles (i.e. ferrofluids). The micromixer prototypes are built using standard microfabrication and simple soft-lithography, and the design can be incorporated as a sub-system into any chemical micro-reactor or a miniaturized biological sensor. The devices achieve mixing virtually instantaneously and may be used to greatly increase mass transport towards chemically or biologically active sites on lab-on-a-chip devices for rapid incubation and highly improved detection sensitivity.

Glioma cell invasion is significantly enhanced in composite hydrogel matrices composed of chondroitin 4- and 4,6-sulfated glycosaminoglycans

Glioblastoma multiforme (GBM) is the most aggressive form of astrocytoma accounting for a majority of primary malignant brain tumors in the United States. Chondroitin sulfate proteoglycans (CSPGs) and their glycosaminoglycan (GAG) side chains are key constituents of the brain extracellular matrix (ECM) implicated in promoting tumor invasion. However, the mechanisms by which sulfated CS-GAGs promote brain tumor invasion are currently unknown. We hypothesize that glioma cell invasion is triggered by the altered sulfation of CS-GAGs in the tumor extracellular environment, and that this is potentially mediated by independent mechanisms involving CXCL12/CXCR4 and LAR signaling respectively. This was tested in vitro by encapsulating the human glioma cell line U87MG-EGFP into monosulfated (4-sulfated; CS-A), composite (4 and 4,6-sulfated; CS-A/E), unsulfated hyaluronic acid (HA), and unsulfated agarose (AG; polysaccharide) hydrogels within microfluidics-based choice assays. Our results demonstrated the enhanced preferential cell invasion into composite hydrogels, when compared to other hydrogel matrices (p<0.05). Haptotaxis assays demonstrated the significantly (p<0.05) faster migration of U87MG-EGFP cells in CXCL12 containing CS-GAG hydrogels when compared to other hydrogel matrices containing the same chemokine concentration. This is likely due to the significantly (p<0.05) greater affinity of composite CS-GAGs to CXCL12 over other hydrogel matrices. Results from qRT-PCR assays further demonstrated the significant (p<0.05) upregulation of the chemokine receptor CXCR4, and the CSPG receptor LAR in glioma cells within CS-GAG hydrogels compared to control hydrogels. Western blot analysis of cell lysates derived from glioma cells encapsulated in different hydrogel matrices further corroborate qRT-PCR results, and indicate the presence of a potential variant of LAR that is selectively expressed only in glioma cells encapsulated in CS-GAG hydrogels. These results suggest that sulfated CS-GAGs may directly induce enhanced invasion and haptotaxis of glioma cells associated with aggressive brain tumors via distinct mechanisms.

Magnetic-Field-Assisted Fabrication and Manipulation of Nonspherical Polymer Particles in Ferrofluid-Based Droplet Microfluidics.

We report a novel magnetic-field-assisted method for the fabrication and manipulation of nonspherical polymer particles within a ferrofluid-based droplet microfluidic device. Shape control and chain assembly of droplets with tunable lengths have been achieved.

Continuous separation of non-magnetic particles through negative magnetophoresis inside ferrofluids

We present a simple, low-cost, effective, and label-free continuous flow non-magnetic microparticle separation scheme in a microfluidic device under static magnetic fields. The separation process is based on negative magnetophoresis and uses water-based ferrofluids. We exploit the difference in particle sizes to achieve continuous binary separation of fluorescent microparticles with high throughput and efficiency. We demonstrate size-based separation (2.1 μm and 9.9 μm; 2.1 μm and 4.8 μm) of microparticles with close to 100% separation efficiency and a minimum of 10 particles/hour throughput. This new approach opens the door for the development of label-free continuous cellular separation in microfluidic devices with high throughput, efficiency, and reliability.

An integrated MEMS ferrofluid pump using insulated metal substrate

A novel ferrofluid micropump utilizing traveling magnetic fields is designed based on previous numerical analysis. A cost-effective fabrication process combining insulated metal substrate etching and soft lithography is used to realize the prototype ferrofluid micropump. Preliminary results show good agreement of pumping characteristics between theory and experiment.

Synchronizing stochastic circadian oscillators in single cells of Neurospora crassa

The synchronization of stochastic coupled oscillators is a central problem in physics and an emerging problem in biology, particularly in the context of circadian rhythms. Most measurements on the biological clock are made at the macroscopic level of millions of cells. Here measurements are made on the oscillators in single cells of the model fungal system, Neurospora crassa, with droplet microfluidics and the use of a fluorescent recorder hooked up to a promoter on a clock controlled gene-2 (ccg-2). The oscillators of individual cells are stochastic with a period near 21 hours (h), and using a stochastic clock network ensemble fitted by Markov Chain Monte Carlo implemented on general-purpose graphical processing units (or GPGPUs) we estimated that >94% of the variation in ccg-2 expression was stochastic (as opposed to experimental error). To overcome this stochasticity at the macroscopic level, cells must synchronize their oscillators. Using a classic measure of similarity in cell trajectories within droplets, the intraclass correlation (ICC), the synchronization surface ICC is measured on >25,000 cells as a function of the number of neighboring cells within a droplet and of time. The synchronization surface provides evidence that cells communicate, and synchronization varies with genotype.

The Magnetohydrodynamic Effect and Its Associated Material Designs for Biomedical Applications: A State-of-the-Art Review

The presented article discusses recent advances in biomedical applications of classical Magnetohydrodynamics (MHD), with a focus on operating principles and associated material considerations. These applications address novel approaches to common biomedical problems from micro-particle sorting for lab-on-a-chip devices to advanced physiological monitoring techniques. 100 papers in the field of MHDs were reviewed with a focus on studies with direct biomedical applications. The body of literature was categorized into three primary areas of research including Material Considerations for MHD Applications, MHD Actuation Devices, and MHD Sensing Techniques. The state of the art in the field was examined and research topics were connected to provide a wide view of the field of biomedical MHDs. As this field develops, the need for advanced simulation and material design will continue to increase in importance in order to further expand its reach to maturity. As the field of biomedical MHDs continues to grow, advances towards micro-scale transitions will continue to be made, maintaining its clinically driven nature and moving towards real-world applications.