Current Pharmaceutical Biotechnology - Volume 11, Issue 4, 2010

It is with great enthusiasm and excitement that I present this special edition dedicated to Micro-Electro-Mechanical-Systems (MEMS) and Nanotechnology for biomedical applications. We have received very unique articles from world class researchers that detail a great number of translational research innovations. Key aspects of the presented articles provide a solid general outlook for the next generation of biomedical devices in both therapeutic and diagnostic applications. The convergence of various engineering and scientific fields has resulted in great micro- and nano-technological innovations, which have already started to affect our way of life. Benefiting from a deeper understanding and improved engineering synergies among fields at the micrometer and nanometer scales, the next generation of biomedical tools will be more sensitive, more specific, faster, more portable, and telemetric. We start this special edition with an outstanding review presented by Dr. Alexander-Katz and co-workers from the Department of Materials Science and Engineering at MIT. His article is focused on multidimensional targeting (MDT), a new revolutionary field that aims to obtain a more thorough understanding of how physiochemical factors from the micrometer to the nanometer scales play a critical role in targeted drug delivery in addition to the use of traditional targeting strategies based on biochemical markers. Such a review provides an insightful perspective on advanced computational methods for complex bio-molecular designs for creation of the next generation of diagnostic and therapeutic nano-molecules. The next superb article provided by Dr. Alexis from Clemson University and Dr. Loo from Nanyang Technological University introduces a fascinating review of nanoparticle based delivery systems. This review focuses on novel bio-imaging and therapeutic applications that use nanoparticle platforms. A comprehensive review describing different routes of synthesis for calcium phosphate nanoparticles is presented, as well as other novel nano-systems and strategies to load pharmacological agents. Issues relating to biostability, cytotoxicity, biodistribution and pharmacokinetics are also reviewed. The article delineates technological applications at the nano-scale level with a salient translational research path to improve disease diagnosis and obtain more effective pharmacological therapies for systemic targeted delivery. The next outstanding review is provided by Dr. Ferrari, Dr. Grattoni, Dr. Fine and co-workers from the Department of Nanomedicine and Biomedical Engineering at the University of Texas Health Science Center at Houston, NanoMedical Systems, Inc., the Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, and Department of Bioengineering at Rice University. They present an exceptionally comprehensive review of nanofluidic devices and systems for biomedical applications. In this remarkable article, a brief survey of delivery modalities and comparison to nanofluidic architectures is presented, followed by a description of nanofluidic transport phenomena. The authors then discuss state-of-the-art nanochannel devices for both diagnostic and therapeutic applications and the possibilities for active implant control. This insightful article also describes key issues related to biocompatibility of nanochannels, as well as the next generation of smart nano-delivery systems capable of biofeedback, representing outstanding innovations in the field of fluidics at the nanometer scale. In the next superb review article, Dr. Rosen from Superior Nanobiosystems, LLC., and Dr. Gurman from the Department of Micro and Nanotechnology from the Argentine National Atomic Energy Commission provide an excellent review of several diagnostics systems based on MEMS and microfluidics, bridging the gap from the nanometer to the micrometer scales. As experienced clinicians, both authors bring a noteworthy perspective of current commercialized medical systems. In addition, various novel bioassays for state-of-the-art point-of-care devices and laboratory equipment using micro and nanotechnologies are presented. The next outstanding review is provided by Dr. Shacham-Diamand and co-workers from the Department of Physical Electronics at Tel-Aviv University, focused on lab-on-chip applications based on the integration of whole-cell sensors with semiconductor and MEMS platforms. This article provides another example of micrometer and nanometer scale level integration. Whole-cell sensors are based on genetically engineered cells designed to sense biochemical signals and express measurable signals in the form of photoluminescence, bioluminescence, or electrochemical response. This captivating work describes a new generation of micro-systems that integrate living cells with integrated circuit (IC) technologies. A review of basic modeling of whole-cell sensors, as well as highlights and challenges for integration are presented....

Targeted drug delivery has traditionally relied on finding highly specific biochemical markers at a target location. However, recent developments in this area have shown that purely physical and physicochemical factors are as important and can be used to aid in the targeting process. Here, we review the physicochemical factors affecting the targeting and delivery process and their relation to established biochemical markers. We refer to this combined approach as multidimensional targeting (MDT). More specifically, we examine the role of MDT factors across different length scales of relevance to the drug delivery pathway. Finally, we conclude with our perspective on the future of this burgeoning area.

Nanotechnologies have the potential to improve current disease diagnosis due to their ability to circulate in the blood and distribute in the body to image tissues and cells or therapeutical applications to deliver a payload. Among nanoparticles with different materials composition, inorganic nanoparticles composed of calcium phosphate have numerous advantages including ease of synthesis, control of physico-chemical properties, strong interactions with their payload, and biocompatibility. In this review we discuss the different routes of synthesis of calcium phosphate nanoparticles, novel systems, strategies to load agents, biostability and cytotoxicity, biodistribution and pharmacokinetics, bio-imaging and therapeutical applications.

Significant recent progress has been made in the development of microfabricated nanofluidic devices for use in the biomedical sciences. Novel nanotechnological approaches have been explored in view of a more individualized medical approach. Much of the development has been fuelled by the advantages derived from utilizing nanoscale phenomena to manipulate fluid samples or mediate drug delivery. As such, we present a comprehensive review of nanochannel technologies, highlighting their potential for diagnostic and therapeutic applications.

There are conditions in clinical medicine demanding critical therapeutic decisions. These conditions necessitate accuracy, rapidity, accessibility, cost-effectiveness and mobility. New technologies have been developed in order to address these challenges. Microfluidics and Micro Electro-Mechanical Systems are two of such technologies. Microfluidics, a discipline that involves processing fluids at the microscale in etched microchannels, is being used to build lab- on-a-chip systems to run chemical and biological assays. These systems are being transformed into handheld devices designed to be used at remote settings or at the bedside. MEMS are microscale electromechanical elements integrated in lab chip systems or used as individual components. MEMS based sensors represents a highly developed field with successful commercialized products currently being incorporated into vitro, ex vivo and in vivo devices. In the present paper several examples of microfluidic devices and MEMS sensors are introduced together with some current examples of commercialized products. Future challenges and trends will be discussed.

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by microsystem- technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the microelectronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

In the past decade, novel fiber structures and material compositions have led to the introduction of new diagnostic and therapeutic tools. We review the structure, the material composition and the fabrication processes behind these novel fiber systems. Because of their structural flexibility, their compatibility with endoscopic appliances and their efficiency in laser delivery, these fiber systems have greatly extended the reach of a wide range of surgical lasers in minimally invasive procedures. Much research in novel fiber-optics delivery systems has been focused on the accommodation of higher optical powers and the extension to a broader wavelength range. Until recently, CO2 laser surgery, renowned for its precision and efficiency, was limited to open surgeries by the lack of delivery fibers. Hollow-core photonic bandgap fibers are assessed for their ability to transmit CO2 laser at surgical power level and for their applications in a range of clinical areas. Current fiber-delivery technologies for a number of laser surgery modalities and wavelengths are compared.

Drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems) represent the next generation of active implantable drug delivery systems. MEMS technology has enabled the scaling down of current delivery modalities to the micrometer and millimeter size. The complementary use of biocompatible materials makes this technology potentially viable for a wide variety of clinical applications. Conditions such as brain tumors, chronic pain syndromes, and infectious abscess represent specialized clinical diseases that will likely benefit most from such drug delivery microdevices. Designing MEMS microdevices poses considerable technical and clinical challenges as devices need to be constructed from biocompatible materials that are harmless to human tissue. Devices must also be miniaturized and capable of delivering adequate pharmacologic payload. Balancing these competing needs will likely lead to the successful application of MEMS drug delivery devices to various medical conditions. This work reviews the various factors that must be considered in optimizing MEMS microdevices for their appropriate and successful application to medical disease.

Implanted medical devices (IMDs), in particular neuro-stimulators, drug delivery chips and cochlear implants are undergoing miniaturization. Some of these miniaturized IMDs are “active” in the sense that they require a power source for operation. In most cases, the ideal power source needs to be an implanted battery of dimensions similar to that of the device. The state-of-the-art of battery miniaturization is reviewed with emphasis on novel Li and Li-ion two- and three-dimensional thin-film microbatteries. It is shown that three-dimensional thin-film batteries may provide a solution to the power requirements of miniaturized IMDs.