Matthew J Hancock - Academia.edu (original) (raw)

Papers by Matthew J Hancock

Bulletin of the American Physical Society, 2011

ABSTRACT A simple and inexpensive bench-top method is presented employing passive mechanisms to g... more ABSTRACT A simple and inexpensive bench-top method is presented employing passive mechanisms to generate centimeters-long gradients of molecules and particles in under a second with only a coated glass slide and a micropipette. By patterning hydrophilic regions on a substrate, a stripe of prepolymer solution is held in place on a glass slide by a hydrophobic boundary. Adding a droplet to one end of this ``pre-wet'' stripe causes a rapid capillary flow that spreads the droplet along the stripe to generate a gradient in the relative concentrations of the droplet and pre-wet solutions. Experiments and theoretical models characterize the flows and gradient profiles and their dependence on the fluid volumes, properties, and stripe geometry. A bench-top rapid prototyping method allows the user to design and fabricate the coated slides using only tape and hydrophobic spray. Gradient biomaterials are produced by crosslinking gradients of prepolymer solutions. Applications include producing a soluble drug gradient over cells in shear-protected microwells, generating a concentration gradient of cells encapsulated in three dimensions within a homogeneous biopolymer, and synthesizing a biomaterial with encapsulated cells exhibiting a gradient in cell spreading.

bioRxiv, 2020

Microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alterna... more Microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both built with the same hiPSC line—to study drug-drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS. These results establish functional...

ABSTRACT A quantitative theory is described for the evolution of sand bars under surface water wa... more ABSTRACT A quantitative theory is described for the evolution of sand bars under surface water waves and is shown to agree well with laboratory experiments. By assuming the slopes of the waves and seabed are comparably gentle, an approximate evolution equation is found for the seabed elevation. In addition to the effects of bedload considered before, it is found that suspended load has a significant effect on sand bar geometry when the seabed is composed of fine sediments. When a second harmonic is significant in the wave field, the growth rate and geometry of sand bars change substantially compared with those under nearly monochromatic waves. When wave reflection is significant, bars and waves interact through the Bragg scattering mechanism. Large regions exist where there is no change to the seabed. Results of recent sand bar experiments in a large wave flume will be presented, for fine and coarse sediment, large and small wave reflection, and for monochromatic and polychromatic waves. In particular, an experiment with a seabed initially consisting of a well mixed sand of two grain sizes demonstrates sediment sorting.

Bulletin of the American Physical Society, 2008

Submitted for the DFD08 Meeting of The American Physical Society Wetting of textured hydrophobic ... more Submitted for the DFD08 Meeting of The American Physical Society Wetting of textured hydrophobic surfaces MATTHEW HANCOCK, JOHN BUSH, MIT-Water repellency in nature and technology typically results from textured hydrophobic surfaces. The roughness elements of such surfaces typically have edges that pin the contact lines of advancing droplets. We present the results of a numerical investigation that relates the contact angle hysteresis and adhesive force to the geometrical, wetting, and elastic properties of the substrate. A number of generic surfaces are considered, including carbon nanotube forests, nano gratings, and insect cuticle. The calculated wetting properties are used to predict common observable quantities such as the critical tilt angle for drop motion.

Frontiers in Pharmacology

Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro ... more Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both created with the same hiPSC line—to study drug–drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS....

Small, 2009

Microstructures that generate shear-protected regions in microchannels can rapidly immobilize cel... more Microstructures that generate shear-protected regions in microchannels can rapidly immobilize cells for cell-based biosensing and drug screening. Here, a two-step fabrication method is used to generate double microgrooves with various depth ratios to achieve controlled double-level cell patterning while still providing shear protection. Six microgroove geometries are fabricated with different groove widths and depth ratios. Two modes of cell docking are observed: cells docked upstream in sufficiently deep and narrow grooves, and downstream in shallow, wide grooves. Computational flow simulations link the groove geometry and bottom shear stress to the experimental cell docking patterns. Analysis of the experimental cell retention in the double grooves demonstrates its linear dependence on inlet flow speed, with slope inversely proportional to the sheltering provided by the groove geometry. Thus, double-grooved microstructures in microfluidic channels provide shear-protected regions for cell docking and immobilization and appear promising for cell-based biosensing and drug discovery.

Small, 2010

Cell-laden hydrogels show great promise for creating engineered tissues. However, a major shortco... more Cell-laden hydrogels show great promise for creating engineered tissues. However, a major shortcoming with these systems has been the inability to fabricate structures with controlled microscale features on a biologically relevant length scale. Here we demonstrate a rapid method for creating centimeter-scale, cell-laden hydrogels through the assembly of shape-controlled microgels. This was achieved by using an approach that uses the liquid-air interface of a hydrophobic solution to drive the assembly of microgels. Cell-laden microgels of specific shapes were randomly placed on the surface of a high density, hydrophobic solution and induced to aggregate and were subsequently crosslinked into macroscale tissue-like structures. The resultant assemblies were cell-laden hydrogel sheets consisting of tightly-packed ordered microgel units. In addition, a hierarchical approach created complex multi-gel building blocks which were then assembled into tissues with precise spatial control over the cell distribution. These data demonstrate that forces at an air-liquid interface can be used to self-assemble spatially controllable, co-cultured tissue-like structures.

Lab on a Chip, 2011

High-throughput preparation of multi-component solutions is an integral process in biology, chemi... more High-throughput preparation of multi-component solutions is an integral process in biology, chemistry and materials science for screening, diagnostics and analysis. Compact microfluidic systems enable such processing with low reagent volumes and rapid testing. Here we present a microfluidic device that incorporates two gradient generators, a tree-like generator and a new microfluidic active injection system, interfaced by intermediate solution reservoirs to generate diluted combinations of input solutions within an 8 × 8 or 10 × 10 array of isolated test chambers. Three input solutions were fed into the device, two to the tree-like gradient generator and one to pre-fill the test chamber array. The relative concentrations of these three input solutions in the test chambers completely characterized device behaviour and were controlled by the number of injection cycles and the flow rate. Device behaviour was modelled by computational fluid dynamics simulations and an approximate analytic formula. The device may be used for twodimensional (2D) combinatorial dilution by adding two solutions in different relative concentrations to each of its three inputs. By appropriate choice of the two-component input solutions, test chamber concentrations that span any triangle in 2D concentration space may be obtained. In particular, explicit inputs are given for a coarse screening of a large region in concentration space followed by a more refined screening of a smaller region, including alternate inputs that span the same concentration region but with different distributions. The ability to probe arbitrary subspaces of concentration space and to control the distribution of discrete test points within those subspaces makes the device of potential benefit for high-throughput cell biology studies and drug screening. † Electronic supplementary information (ESI) available. See

Journal of Geophysical Research, 2008

Drug Discovery Today, 2012

Recent advances in tissue engineering have enabled the development of microscale biomimetic 'orga... more Recent advances in tissue engineering have enabled the development of microscale biomimetic 'organ on a chip' tissue models which have the potential to make an important impact on the various stages of drug discovery and toxicity testing. Developing biologically relevant models of human tissues and organs is an important enabling step for disease modeling and drug discovery. Recent advances in tissue engineering, biomaterials and microfluidics have led to the development of microscale functional units of such models also referred to as 'organs on a chip'. In this review, we provide an overview of key enabling technologies and highlight the wealth of recent work regarding on-chip tissue models. In addition, we discuss the current challenges and future directions of organ-on-chip development.

Coastal Engineering, 2007

Classical and Quantum Gravity, 2000

The Canadian Journal of Chemical Engineering, 2010

During tissue morphogenesis and homeostasis, cells experience various signals in their environmen... more During tissue morphogenesis and homeostasis, cells experience various signals in their environments, including gradients of physical and chemical cues. Spatial and temporal gradients regulate various cell behaviours such as proliferation, migration, and differentiation during development, inflammation, wound healing, and cancer. One of the goals of functional tissue engineering is to create microenvironments that mimic the cellular and tissue complexity found in vivo by incorporating physical, chemical, temporal, and spatial gradients within engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques from material science, microscale engineering, and microfluidics are used to synthesise biomimetic hydrogels with encapsulated cells and tailored microenvironments. In particular, a host of methods exist to incorporate micrometer to centimetre scale chemical and physical gradients within hydrogels to mimic the cellular cues found in vivo. In this review, we draw on specific biological examples to motivate hydrogel gradients as tools for studying cell-material interactions. We provide a brief overview of techniques to generate gradient hydrogels and showcase their use to study particular cell behaviours in two-dimensional (2D) and 3D environments. We conclude by summarizing the current and future trends in gradient hydrogels and cell-material interactions in context with the long-term goals of tissue engineering. Lors de la morphogenèse et l'homéostase tissulaires, les cellules perçoivent divers signaux dans leurs environnements, y compris des gradients de signaux physiques et chimiques. Les gradients spatiaux et temporels règlent les divers comportements des cellules, comme la prolifération, la migration et la différentiation pendant le développement, l'inflammation, la guérison des plaies et le cancer. Un des objectifs de l'ingénierie tissulaire fonctionnelle est de créer des microenvironnements qui imitent la complexité cellulaire et tissulaire que l'on trouve in vivo en incorporant des gradients physiques, chimiques, temporels et spatiaux au sein d'échafaudages tridimensionnels (3D)élaborés. Les hydrogels sont des matières idéales pour leséchafaudages tissulaires 3D qui imitent la matrice extracellulaire. Diverses techniques des sciences des matières, de l'ingénierie de microéchelle et de la microfluidique sont utilisées pour synthétiser les hydrogels biomimétiques avec des cellules encapsulées et des microenvironnements sur mesure. En particulier, une série de méthodes existent pour incorporer des gradients chimiques et physiques d'échelle de micromètreà centimètre au sein d'hydrogels pour imiter les signaux cellulaires que l'on trouve in vivo. Dans cette révision, nous tirons des exemples biologiques précis pour motiver les gradients d'hydrogels comme outils pourétudier les interactions cellule-matière. Nous fournissons un bref aperçu des techniques visantà produire des hydrogels de gradient et présenter leur utilisation pourétudier des comportements cellulaires particuliers dans des environnements bidimensionnels et tridimensionnels. Nous concluons en résumant les tendances actuelles età venir en hydrogels de gradient et interactions cellule-matière conformément aux objectifsà long terme de l'ingénierie tissulaire.

Biotechnology and Bioengineering, 2011

Combinatorial material synthesis is a powerful approach for creating composite material libraries... more Combinatorial material synthesis is a powerful approach for creating composite material libraries for the high-throughput screening of cell-material interactions. Although current combinatorial screening platforms have been tremendously successful in identifying target (termed "hit") materials from composite material libraries, new material synthesis approaches are needed to further optimize the concentrations and blending ratios of the component materials. Here we employed a microfluidic platform to rapidly synthesize composite materials containing crossgradients of gelatin and chitosan for investigating cell-biomaterial interactions. The microfluidic synthesis of the cross-gradient was optimized experimentally and theoretically to produce quantitatively controllable variations in the concentrations and blending ratios of the two components. The anisotropic chemical compositions of the gelatin/chitosan cross-gradients were characterized by Fourier transform infrared spectrometry and X-ray photoelectron spectrometry. The three-dimensional (3D) porous gelatin/chitosan cross-gradient materials were shown to regulate the cellular morphology and proliferation of smooth muscle cells (SMCs) in a gradientdependent manner. We envision that our microfluidic cross-gradient platform may accelerate the material development processes involved in a wide range of biomedical applications.

Biomaterials, 2011

We present a simple bench-top technique to produce centimeter long concentration gradients in bio... more We present a simple bench-top technique to produce centimeter long concentration gradients in biomaterials incorporating soluble, material, and particle gradients. By patterning hydrophilic regions on a substrate, a stripe of prepolymer solution is held in place on a glass slide by a hydrophobic boundary. Adding a droplet to one end of this "pre-wet" stripe causes a rapid capillary flow that spreads the droplet along the stripe to generate a gradient in the relative concentrations of the droplet and pre-wet solutions. The gradient length and shape are controlled by the pre-wet and droplet volumes, stripe thickness, fluid viscosity and surface tension. Gradient biomaterials are produced by crosslinking gradients of prepolymer solutions. Demonstrated examples include a concentration gradient of cells encapsulated in three dimensions (3D) within a homogeneous biopolymer and a constant concentration of cells encapsulated in 3D within a biomaterial gradient exhibiting a gradient in cell spreading. The technique employs coated glass slides that may be purchased or custom made from tape and hydrophobic spray. The approach is accessible to virtually any researcher or student and should dramatically reduce the time required to synthesize a wide range of gradient biomaterials. Moreover, since the technique employs passive mechanisms it is ideal for remote or resource poor settings.

Advanced Functional Materials, 2012

In Nature, directional surfaces on insect cuticle, animal fur, bird feathers, and plant leaves ar... more In Nature, directional surfaces on insect cuticle, animal fur, bird feathers, and plant leaves are comprised of dual micro-nanoscale features that tune roughness and surface energy. This feature article summarizes experimental and theoretical approaches for the design, synthesis and characterization of new bioinspired surfaces demonstrating unidirectional surface properties. The experimental approaches focus on bottom-up and top-down synthesis methods of unidirectional micro-and nanoscale films to explore and characterize their anomalous features. The theoretical component of the review focuses on computational tools to predict the physicochemical properties of unidirectional surfaces.

Journal of Fluid Mechanics, 2002

We present the results of a combined theoretical and experimental investigation of laminar vertic... more We present the results of a combined theoretical and experimental investigation of laminar vertical jets impinging on a deep fluid reservoir. We consider the parameter regime where, in a pure water system, the jet is characterized by a stationary field of capillary waves at its base. When the reservoir is contaminated by surfactant, the base of the jet is void of capillary waves, cylindrical and quiescent: water enters the reservoir as if through a rigid pipe. A theoretical description of the resulting fluid pipe is deduced by matching extensional plug flow upstream of the pipe onto entry pipe flow within it. Theoretical predictions for the pipe height are found to be in excellent accord with our experimental results. An analogous theoretical description of the planar fluid pipe expected to arise on a falling fluid sheet is presented.