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Author: Dmitry A Markov (15)


Jan
2018

A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine.

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Dec
2016

Understanding blood-brain barrier responses to inflammatory stimulation (such as lipopolysaccharide mimicking a systemic infection or a cytokine cocktail that could be the result of local or systemic inflammation) is essential to understanding the effect of inflammatory stimulation on the brain. It is through the filter of the blood-brain barrier that the brain responds to outside influences, and the blood-brain barrier is a critical point of failure in neuroinflammation. It is important to note that this interaction is not a static response, but one that evolves over time.

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Sep
2015

The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier.

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Dec
1969

The blood-brain barrier (BBB) dynamically controls exchange between the brain and the body, but this interaction cannot be studied directly in the intact human brain or sufficiently represented by animal models. Most existing in vitro BBB models do not include neurons and glia with other BBB elements and do not adequately predict drug efficacy and toxicity. Under the National Institutes of Health Microtissue Initiative, we are developing a three-dimensional, multicompartment, organotypic microphysiological system representative of a neurovascular unit of the brain.

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Feb
2014

Polydimethylsiloxane (PDMS) is a commonly used polymer in the fabrication of microfluidic devices due to such features as transparency, gas permeability, and ease of patterning with soft lithography. The surface characteristics of PDMS can also be easily changed with oxygen or low pressure air plasma converting it from a hydrophobic to a hydrophilic state. As part of such a transformation, surface methyl groups are removed and replaced with hydroxyl groups making the exposed surface to resemble silica, a gas impermeable substance.

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Mar
2013

The sophistication and success of recently reported microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may significantly augment the current drug development pipeline and lead to advances in systems biology. Physiologically realistic live microHuman (μHu) and milliHuman (mHu) systems operating for weeks to months present exciting and important engineering challenges such as determining the appropriate size for each organ to ensure appropriate relative organ functional activity, achieving appropriate cell density, providing the requisite universal perfusion media, sensing the breadth of physiological responses, and maintaining stable control of the entire system, while maintaining fluid scaling that consists of ~5 mL for the mHu and ~5 μL for the μHu. We believe that successful mHu and μHu systems for drug development and systems biology will require low-volume microdevices that support chemical signaling, microfabricated pumps, valves and microformulators, automated optical microscopy, electrochemical sensors for rapid metabolic assessment, ion mobility-mass spectrometry for real-time molecular analysis, advanced bioinformatics, and machine learning algorithms for automated model inference and integrated electronic control.

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Nov
2012

We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system.

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Oct
2011

Morphogenesis is a fundamental process by which new blood vessels are formed during angiogenesis. The ability to control angiogenesis would lead to improvements in tissue engineering constructions; indeed, the study of angiogenesis has numerous clinical applications, for example, in the investigation of metastatic cancer, peripheral and coronary vascular disease, and wound healing. Conventional in vitro organotypic cell culture approaches to these studies are limited primarily by their reliance on microvascular vessel formation through a random process of morphogenesis that lacks the spatial reproducibility and orientation needed for high-throughput drug testing.

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May
2010

Microbial growth and transport in porous media have important implications for the quality of groundwater and surface water, the recycling of nutrients in the environment, as well as directly for the transmission of pathogens to drinking water supplies. Natural porous media is composed of an intricate physical topology, varied surface chemistries, dynamic gradients of nutrients and electron acceptors, and a patchy distribution of microbes. These features vary substantially over a length scale of microns, making the results of macro-scale investigations of microbial transport difficult to interpret, and the validation of mechanistic models challenging.

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Feb
2010

We describe a simple and reliable fabrication method for producing multiple, manually activated microfluidic control valves in polydimethylsiloxane (PDMS) devices. These screwdriver-actuated valves reside directly on the microfluidic chip and can provide both simple on/off operation as well as graded control of fluid flow. The fabrication procedure can be easily implemented in any soft lithography lab and requires only two specialized tools-a hot-glue gun and a machined brass mold.

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Sep
2007

Free-solution, label-free molecular interactions were investigated with back-scattering interferometry in a simple optical train composed of a helium-neon laser, a microfluidic channel, and a position sensor. Molecular binding interactions between proteins, ions and protein, and small molecules and protein, were determined with high dynamic range dissociation constants (Kd spanning six decades) and unmatched sensitivity (picomolar Kd's and detection limits of 10,000s of molecules). With this technique, equilibrium dissociation constants were quantified for protein A and immunoglobulin G, interleukin-2 with its monoclonal antibody, and calmodulin with calcium ion Ca2+, a small molecule inhibitor, the protein calcineurin, and the M13 peptide.

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Dec
2004

Quantification of protein-protein and ligand-substrate interactions is central to understanding basic cellular function and for evaluating therapeutics. To mimic biological conditions, such studies are best executed without modifying the proteins or ligands (i.e.

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Nov
2004

The ability to measure fluid velocity within picoliter volumes or on-chip noninvasively, is important toward fully realizing the potential of microfluidics and micrototal analysis systems, particularly in applications such as micro-high-performance liquid chromatography (HPLC) or in metering mixing where the flow rate must be quantified. Additionally, these measurements need to be performed directly on moving fluids in a noninvasive fashion. We presented here the proof of principle experiments showing nonintrusive fluid flow measurements can be accomplished on-chip using a pump and probe configuration with backscattering interferometry.

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Mar
2002

A new method of fringe interrogation based on Fourier analysis was implemented and tested for a capillary polarimetry detector. It has significant advantages over the previously employed depth of modulation (DOM) approach, including speed and alignment insensitivity. The new and old methods were compared using a set of interference fringes typically used to facilitate nanoliter volume polarimetric determinations.

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