Silica Nanochannel Surface Effect on Monosaccharide Transport

The interface of silica nanochannel of 10 nm was studied by molecular modeling and experimental methods. Molecular Dynamics study on glucose solution revealed that 2–3 nm of interface solution to silica walls has reduced glucose diffusivity. That reduction affects the effective diffusivity of glucose in silica nanochannel. Experimental results show Fickian-like release of glucose through 13 nm nanochannel. Molecular modeling and experimental results suggest that glucose is not sufficiently confined to possess non-Fickian behavior.

Micropattern Effect on Breast Cancer Cells Behavior on Isotropically Etched Silicon Microenvironments

In this paper we are investigating three dimensional (3-D) silicon-based microenvironments as potential platforms for breast cancer diagnostics. We have developed isotropically etched microstructures with a wide range of geometrical patterns for this purpose. Our results indicate that with the etched surface ratio of ∼65%, it is possible to capture 80–90% of the cancer cells within each silicon chip. After treatment of the cells with mitomycin C (to block the cell growth) more number of the cells are trapped inside the etched features for longer cultures times (72 h) suggesting that there is a directed motility and attraction of the cells toward the etched cavities and by optimally designing the etched features, the proposed platforms can be potentially used for diagnostics purposes.

Manipulation of Clinical Materials Using AC Electrokinetics

AC electrokinetics is a promising approach for sample preparation and reaction enhancement in lab-on-a-chip devices. However, relative little has been done on the electrokinetic manipulation of physiological fluids and buffers with similar properties, such as conductivity. Herein, electrokinetic manipulation of fluids with a wide range of conductivities has been studied as a function of voltage and frequency. AC electrothermal flow is determined to dominate the fluid motion when the applied frequency of the AC potential is above 100 kHz. Interestingly, experimental data deviate from theoretical prediction for fluids with high conductivities (> 1 Sm−1). The deviation can be understood by voltage modulated electrochemical reactions and should be accounted for when manipulating clinical materials with high conductivities. The study will provide useful in sights in designing lab-on-a-chip devices for manipulating clinical samples in the future.

Characterization of Biosensor Detection Process at Ultra-Low Concentration Through a Stochastic Particle Model

Biosensor detection process involves binding between biomolecules in a solution and a functionalized sensor surface. These sensors are time and cost efficient, sensitive, and enable new applications in medicine, drug design, and environmental monitoring. In literatures, various biosensor designs have been proposed, such as planar electrodes, nanowire, and nanospheres for different applications. However, to fully realize the potentials of these biosensors for biomarker/nanoparticle detection, several challenges must be addressed. In particular, ultra-sensitive biosensors are needed for detection of ultra-low concentration biomarkers such as cancer markers for early disease detection. The goal of this paper is to understand the diffusion process of biomarkers in a liquid solution and the binding with nanosensor surface through a stochastic particle model.

Hyperthermic Cytotoxicity Induced by Noninvasive Radiofrequency Field Exposure After Delivery of EGFR Family Targeted Gold Nanoparticles

Noninvasive radiofrequency (RF) fields heat metal nanoparticles in a concentration dependent fashion. Gold nanoparticles are especially interesting for biomedical applications because they not only heat well, but they have an established biosafety profile. Antibody-targeted gold nanoparticles have been used to induce hyperthermic cytotoxicity when exposed to RF fields. Two carcinoma cells lines, Panc-1 and Hep3B, were individually treated with 100 nM panitumumab and trastuzumab antibody conjugated 10 nm gold nanoparticles and subsequently exposed to an RF field for a total generator power of ∼100 kJ. Two days later, control cells treated with antibody labeled gold nanoparticles, but not exposed to the RF field, maintained an average viability of 92.1% ± 2.5% for Hep 3B cells and 89.1% ± 2.1% for Panc-1 cells based on flow cytometry. Panc-1 cells treated the same way with subsequent RF field exposure had viability less than 80% (p ∼ 0.001). Hep3B cells showed a similar decrease in viability after trastuzumab-gold treatment (74.5% ± 6.9%), but not panitumumab. This demonstrates a new and developing use of antibodies, specifically, against EGFR family targets.

Protein Molecules as Natural Nano Bio Devices: Mobility Analysis

Proteins are nature’s nano-robots in the form of functional molecular components of living cells. The function of these natural nano-robots often requires conformational transitions between two or more native conformations that are made possible by the intrinsic mobility of the proteins. Understanding these transitions is essential to the understanding of how proteins function, as well as to the ability to design and manipulate protein-based nano-mechanical systems [1]. Modeling protein molecules as kinematic chains provides the foundation for developing powerful approaches to the design, manipulation and fabrication of peptide based molecules and devices. Nevertheless, these models possess a high number of degrees of freedom (DOF) with considerable computational implications. On the other hand, real protein molecules appear to exhibits a much lower mobility during the folding process than what is suggested by existing kinematic models. The key contributor to the lower mobility of real proteins is the formation of Hydrogen bonds during the folding process.

A Micro-Architectural Based Structural Model for Elastomeric Electrospun Scaffolds

Interest in electrospun polymeric nano-microfibers for tissue engineering applications has rapidly grown during the last decade. In spite of this technique’s flexibility and ability to form complex fiber assemblies, additional studies are required to elucidate how the fibrous microstructure translates into specific tissue (or meso-scale) level mechanical behavior. Deterministic structural models can quantify how key structures contribute to the mechanical response as a function of bulk deformation across multiple scales, as well as provide a better understanding of cellular mechanical response to local micro-structural deformations. Our ultimate aim is to utilize such models to assist tissue engineering scaffold design. In the current work, we present a novel approach to automatically quantify key micro-architectural descriptors (fiber overlaps, connectivity, orientation, and diameter) from SEM images of electrospun poly (ester urethane) urea (PEUU) to recreate statistically equivalent scaffold mechanical models. An appropriate representative volume element (RVE) size was determined by quantifying the point of stabilization of the architectural descriptors over image areas of increasing size. Material models were then generated specifying: fiber overlap density, fiber orientation, connectivity and fiber diameter. Macro-meso mechanical response was predicted via FEM simulations.

Electrostatic Self-Assembly of Functionalized Nanodiamonds and Their Binding Capacity With Doxorubicin Drugs

While cancers have no known cure, some of them can be successfully treated with the combination of surgery and systematic therapy. In general, systemic/widespread chemotherapy is usually injected into the bloodstream to attempt to target cancer cells. Such procedure often imparts devastating side effects because cancer drugs are nonspecific in activity, and transporting them throughout the bloodstream further reduces their ability to target the right region. This means that they kill both healthy and unhealthy cells. It has been observed that the physiological conditions of the fluids around living cells can be characterized by pH, and the magnitude of pH around a living cell is different from cancerous cells. Moreover, a multiscale anatomy of carcinoma will reveal that the microstructure of cancer cells contains some characteristic elements such as specific biomarker receptors and DNA molecules that exclusively differentiate them from healthy cells. If these cancer specific ligands can be intercalated by some functional molecules supplied from an implantable patch, then the patch can be envisioned to serve as a complementary technology with current systemic therapy to enhance localized treatment efficiency, minimize excess injections/surgeries, and prevent tumor recurrence. The broader objective of our current research is to capture some fundamental insights of such drug delivery patch system. It is envisioned that the essential components of the device is nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs. In its simplest form, self-assembled nanodiamonds - functionalized or pristine, and DOX molecules are contained inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device include: 1. A precise identification of the equilibrium structure and self assembled morphology of nanodiamonds, 2. Fundamental understanding of the drug adsorption and desorption process to and from NDs, and 3. The rate of drug release through the parylene buffers. The structure of the nanodiamond (ND) is crucial to the adsorption and desorption of drug molecules because it not only changes the self-assembly configuration but also alters the surface electrostatics. To date, the structure and electrostatics of NDs are not yet well understood. A density functional tight binding theory (DFTB) study on smaller [2] NDs suggests a facet dependent charge distributions on ND surfaces. These charges are estimated by Mulliken Analysis [1]. Using the charges for smaller NDs (∼valid for 1–3.3 nm dia ND) we first projected surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND), and it has been found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. These projected charges are then utilized to obtain the self assembled structure of pristine TONDs from Molecular Dynamics (MD) simulations [4] as shown in Fig. 1. The opposite charges on the [100] and [111] face invoked electrostatic attractions among the initially isolated NDs and a network of nanodiamond agglutinates are formed as evidenced in Fig. 1(b). This study confirms why as manufactured NDs are found in agglomerated form. The study also suggests that a large fraction of ND surfaces become unavailable for drug absorption as many of the [100] faces are coherently connected to [111] faces. As a result, it can be perceived that effective area for drug adsorption on ND surfaces will be less compared to theoretical prediction which suggests that a 4nm TOND may contain as high 360 drug molecules on its surface [5]. It has been observed that as manufactured NDs may contain a variety of functional groups, and currently, we are studying the mechanism of self-assembly for functionalized nanodiamonds so that we understand the role of functional groups. The next phase of calculation involves binding of the DOX to the NDs. Essentially, the understanding of drug absorption and desorption profile at a controlled rate to and from NDs is the most critical part of the device design. Some recent quantum calculation suggests that part of NDs and drug molecules contain opposite charges at their surfaces; it has been a natural interpretation that interactions between ND and drug molecules should be straight-forward — NDs should attract to drugs as soon as they come closure. Recent experiments [6], however, suggest that NDs usually do not interact with drug molecules in the presence of neutral solutions. Addition of NaCl in the solution improves the interaction dramatically. In the first part of the study, we [3–5] have studied the interaction of single DOX molecules with TOND surfaces via MD simulation. As shown in Fig. 2, this study suggests that DOX molecules first arrange them around the preferential sites on nanodiamonds (e.g. around the [111] face) and then spontaneously attach on the surface. It is also observed that only DOX molecule is attached per facets of TONDs. It can be noted that each TOND has 6 [100] face and 8 [111] faces. Figure 3 shows the energy minimization process during the DOX-ND interaction. It can be noted that these simulations have been performed in vacuum environment. In order to see how DOX interacts in solution media, another set of simulations have been conducted where “vacuum” environment have been replaced with solution media of different pH. Moreover, functionalization on the ND surfaces will create a different environment for the DOX molecules. Research is underway to capture the fundamental physics on the DOX loading and release to and from functionalized nanodiamonds. Once we understand the essential physics of drug loading and unloading, in the future we plan to model diffusion controlled drug release through ND coated film device by incorporating the multiscale science learned from the current study. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.

A Study of Bifurcation Design Used in CD-ELISA Micro-Fluidic Platform

Enzyme-linked immunosorbent assays (ELISA), one of the most common immunoassays, is widely used for detection and quantification of chemical and biological molecules and is becoming more and more important in clinical diagnostics, food safety testing, and environmental monitoring. A major challenge in developing the CD-ELISA is to split the flow (e.g., bio-reagents) evenly on the micro-channels. The Coriolis force resultant from CD rotation can disturb the flow in the splitter region and thus cause the failure mode in delivering the solution from each reservoir in a pre-specified manner. In this study, we investigate on the effects of inlet pressure and Coriolis force on the splitting ratio under two splitter structures. The analysis is based on the incompressible Navier-Stokes equation and the simulation results agree well with our experimental work.

DNA Damage by Nanoparticles

Nanoparticles (NPs) have provided significant technological advancements including bactericidal agents in food processing, and treatment of cancer tumors. However, there is a darkside. Over the past decade, experiments [1,2] have shown NPs to be a health risk by inducing DNA damage that can lead to cancer.