53 research outputs found
Design and Implementation of Functional Nanoelectronic Interfaces With Biomolecules, Cells, and Tissue Using Nanowire Device Arrays
No full textNanowire FETs (NWFETs) are promising building blocks for nanoscale bioelectronic interfaces with cells and tissue since they are known to exhibit exquisite sensitivity in the context of chemical and biological detection, and have the potential to form strongly coupled interfaces with cell membranes. We present a general scheme that can be used to assemble NWs with rationally designed composition and geometry on either planar inorganic or biocompatible flexible plastic surfaces. We demonstrate that these devices can be used to measure signals from neurons, cardiomyocytes, and heart tissue. Reported signals are in millivolts range, which are equal to or substantially greater than those recorded with either planar FETs or multielectrode arrays, and demonstrate one unique advantage of NW-based devices. Basic studies showing the effect of device sensitivity and cell/substrate junction quality on signal magnitude are presented. Finally, our demonstrated ability to design high-density arrays of NWFETs enables us to map signal at the subcellular level, a functionality not enabled by conventional microfabricated devices. These advances could have broad applications in high-throughput drug assays, fundamental biophysical studies of cellular function, and development of powerful prosthetics
Magnetically Triggered Nanocomposite Membranes: A Versatile Platform for Triggered Drug Release
No full textAuthor Manuscript 2012 March 9.Drug delivery devices based on nanocomposite membranes containing thermoresponsive nanogels and superparamagnetic nanoparticles have been demonstrated to provide reversible, on−off drug release upon application (and removal) of an oscillating magnetic field. We show that the dose of drug delivered across the membrane can be tuned by engineering the phase transition temperature of the nanogel, the loading density of nanogels in the membrane, and the membrane thickness, allowing for on-state delivery of model drugs over at least 2 orders of magnitude (0.1−10 μg/h). The zero-order kinetics of drug release across the membranes permit drug doses from a specific device to be tuned according to the duration of the magnetic field. Drugs over a broad range of molecular weights (500−40000 Da) can be delivered by the same membrane device. Membrane-to-membrane and cycle-to-cycle reproducibility is demonstrated, suggesting the general utility of these membranes for drug delivery.Ruth L. Kirschstein National Research Service AwardNational Institutes of Health (U.S.) (Award F32GM096546
Nanowired three-dimensional cardiac patches
No full textEngineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds1, 2, 3. These biomaterials, which are usually made of either biological polymers such as alginate4 or synthetic polymers such as poly(lactic acid) (PLA)5, help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit6. Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.National Institutes of Health (U.S.) (NIH, grant GM073626)National Institutes of Health (U.S.) (NIH, grant DE13023)National Institutes of Health (U.S.) (NIH, grant DE016516)American Heart Association (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award (no. F32GM096546)
A Stiff Injectable Biodegradable Elastomer
No full textInjectable materials often have shortcomings in mechanical and drug-eluting properties that are attributable to their high water contents. A water-free, liquid four-armed PEG modified with dopamine end groups is described which changes from liquid to elastic solid by reaction with a small volume of Fe3+ solution. The elastic modulus and degradation times increase with increasing Fe3+ concentrations. Both the free base and the water-soluble form of lidocaine can be dissolved in the PEG4-dopamine and released in a sustained manner from the cross-linked matrix. PEG4-dopamine is retained in the subcutaneous space in vivo for up to 3 weeks with minimal inflammation. This material's tailorable mechanical properties, biocompatibility, ability to incorporate hydrophilic and hydrophobic drugs and release them slowly are desirable traits for drug delivery and other biomedical applications.National Institute on Deafness and Other Communication Disorders (U.S.) (NIDCD R21 DC 009986)National Institutes of Health (U.S.) (NIH Ruth L. Kirschstein National Research Service Award (no. F32GM096546))National Institutes of Health (U.S.) (NIH R01 EB00244
Near-infrared-actuated devices for remotely controlled drug delivery
No full textA reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.National Institutes of Health (U.S.) (Grant GM073626)Massachusetts Institute of Technology. Laser Biomedical Research Center (Sanofi Aventis (Firm) Biomedical Innovation Funding Award)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service AwardNational Institutes of Health (U.S.) (Grant F32GM096546
Nanowire-Based Nanoelectronic Devices in the Life Sciences
No full textAbstractThe interface between nanosystems and biosystems is emerging as one of the broadest and most dynamic areas of science and technology, bringing together biology, chemistry, physics, biotechnology, medicine, and many areas of engineering. The combination of these diverse areas of research promises to yield revolutionary advances in healthcare, medicine, and the life sciences through the creation of new and powerful tools that enable direct, sensitive, and rapid analysis of biological and chemical species. Devices based on nanowires have emerged as one of the most powerful and general platforms for ultrasensitive, direct electrical detection of biological and chemical species and for building functional interfaces to biological systems, including neurons. Here, we discuss representative ex amples of nanowire nanosensors for ultrasensitive detection of proteins and individual virus particles as well as recording, stimulation, and inhibition of neuronal signals in nanowire-neuron hybrid structures.</jats:p
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