BioMEMS

Explosive growth in the field of microsystem technology (MST) has introduced a variety of promising products in major disciplines from microelectronics to life sciences. Especially the life sciences and health care business was, and is expected to be a major market for MST products. Undoubtedly the merging of biological sciences with micro- and nanoscience will create a scientific and technological revolution in future. Microminiaturization of devices, down to the nanoscale, approaching the size of biological structures, will be a prerequisite for the future success of life sciences. Bioanalytical and therapeutic micro- and nanosystems will be mandatory for system biologists in the long run, to obtain insight into morphology, the function and the interactive processes of the living system. With such a deeper understanding new and personalized drugs could be developed leading to a revolution in life sciences. Today, microanalytical devices are used in clinical analytics or molecular biology as gene chips. In parallel, standard microbiomedical products are employed in the intensive care and surgical theatre, mainly for monitoring and implantation purposes. The gap between these two different scientific fields will be closed, however, as soon as functional micro devices can be produced, allowing a deeper view into the function of cells and whole organisms.

Here, a new discipline evolved which focuses on microsystems for living systems called "BIOMEMS". In this review at a glance the exciting field of bio-microsystems, from their beginnings to indicators of future successes are presented. It will also show that a broad penetration of micro and nano technologies into biology and medicine will be mandatory for future scientific and new product development progress in life science.

Inhalt

• EARLY BIOMEMS, MULTI-SENSOR NEUROPROBES. 1. INTRODUCTION . 2. EVOLUTION OF MICRO-SENSOR ARRAY DESIGNS FOR MEDICAL RESEARCH. 2.1.Electrical signal monitoring. 2.2.Sensor Design Evolution: from 2D to 3D. 2.3.Chamber-Type Electrochemical Oxygen Sensors. 3. OTHER APPLICATIONS - THE FIRST MICRO-FLUIDIC DEVICE. 4. CONCLUSION. 5. REFERENCES.- MULTI-PARAMETER BIOMEMS FOR CLINICAL MONITORING. 1. INTRODUCTION. 2. BIOSENSORS. 2.1.Principle of Biosensors. 2.2.Amperometric Biosensors. 2.3.Aspects of miniaturization and integration. 3. CLINICAL MONITORING. 3.1.Multi-analyte measurement. 3.2.Microdialysis. 3.3.BioMEMS for clinical monotoring. 3.4.Multiparameter monitoring. 3.5.Applications.. 4. CONCLUSIONS AND OUTLOOK. 5. REFERENCES.- BIOMEDICAL MICRODEVICES FOR NEURAL IMPLANTS. 1. INTRODUCTION TO NEURAL IMPLANTS. 2. ANATOMICAL AND BIOPHYSICAL FUNDAMENTALS. 2.1.Peripheral Nerve Anatomy. 2.2.Mechanisms of Peripheral Nerve Damage. 2.3.Excitability of Nerves. 2.4.Electrical Modeling of the Nerve Membrane. 2.5.Propagation of Action Potentials. 2.6.Extracellular Stimulation of Nerve Fibres. 2.7.Selective Activation of Nerve Fibres. 3. CLINICAL IMPLANTS. 3.1.Electrodes - The Key Component in Neural Prostheses. 3.2.Cardiac Pacemakers. 3.3.Implantable Defibrillators. 3.4.Cochlea Implants. 3.5.Phrenic Pacemakers. 3.6.Grasp Neuroprostheses . 3.7.Neuroprostheses for gait and posture. 3.8.Spinal Root Stimulator. 3.9.Drop Foot Stimulator. 3.10.Neuromodulation. 3.11.Deep Brain Stimulation. 3.12.Vagal Nerve Stimulation. 4. THE CHALLENGE OF MICROIMPLANTS. 5. VISION PROSTHESES. 5.1.Cortical Vision Prostheses. 5.2.Optic Nerve Vision Prosthesis . 5.3.Retinal Implants. 5.4.Conclusions on Vision Prostheses. 6. PERIPHERERAL NERVE INTERFACES. 6.1.Non-Invasive Nerve Interfaces. 6.2."Semi"-Invasive Interfaces. 6.3.Invasive Interfaces. 6.4.Biohybrid Approaches. 7.FUTURE APPLICATIONS. 7.1.Interfacing the Brain. 7.2.Spinal Cord Implants. 7.3.Multimodal Neural Implants. 8.CONCLUDING REMARKS. 9.NEURAL IMPLANTS: BOON OR BANE? 10. REFERENCES.- MICROFLUIDIC PLATFORMS . 1.INTRODUCTION. 2. WHAT IS A MICROFLUIDIC PLATFORM. 3. EXAMPLES OF MICROFLUIDIC PLATFORMS. 3.1.PDMS based Microfluidics for Large Scale Integration ("Fluidigm platform"). 3.2.Microfluidics on a Rotating Disk ("Lab-on-a-Disk"). 3.3.Droplet based microfluidics (DBM). 3.4.Non-contact liquid Dispensing. 4.CONCLUSION. REFERENCES.- DNA BASED BIO-MICRO-ELECTRONIC-MECHANICAL-SYSTEMS. 1.INTRODUCTION. 1.1.The unique features of nucleic acids. 1.2.Lab-on-the-Chip. 1.3.Biochemical reaction chains for integration: biosensors and the "lab-biochip". 2.MICROARRAYS AND BIOCHIPS BASED ON DNA. 2.1.The typical microarray experiment. 2.2.Manufacturing of Microarrays. 2.3Transcription Analysis. 2.4.Oligonucleotide Arrays for sequencing. 2.5.Active arrays. 2.6.Integrated PCR. 3. NANOBIOTECHNOLOGY: DNA AS MATERIAL. 3.1.DNA directed immobilisation and nucleic acid tags. 3.2.DNA for regular structures. 3.3.DNA to structure surfaces. 3.4.Metallisation of DNA for electronic circuits. 4.REFERENCES SEPARATION AND DETECTION ON A CHIP. 1.INTRODUCTION. 2.THEORY OF CAPILLARY ELECTROPHORESIS ON A CE-CHIP. 2.1.Mobility of ions. 2.2.Electroosmotic flow. 3.JOULE HEATING IN MICROFABRICATED DEVICES. 3.1.Separation efficiency of a CE-chip. 3.2.Separation of biomacromolecules and particles. 4.BUILDING BLOCKS OF CE-CHIP DEVICES. 4.1.Wafer materials, micromachining and wafer bonding. 4.2.Power supplies, pumping, injection and channel geometries. 4.3.Detection strategies. 5.SELECTED EXAMPLES FOR CE ON A CHIP. 6.DIELECTROPHORESIS. 7.OUTLOOK. 8.REFERENCES.- PROTEIN MICROARRAYS : APPLICATIONS AND FUTURE CHALLENGES. 1.INTRODUCTION. 2.FORWARD-PHASE PROTEIN MICROARRAYS. 2.1.Protein-Expression Analysis Using Protein Microarrays. 2.2.Protein Interaction Microarrays. 3.REVERSE MICROARRAYS. 4.OUTLOOK. 5.BIBLIOGRAPHY .- LAB-ON-A-CHIP SYSTEMS FOR CELLULAR ASSAYS . 1.INTRODUCTION . 2.DESIGN AND FABRICATION OF CHIPS FOR CELL BASED ASSAYS. 3.CELL CULTURE ON CHIPS AND MICROFLUIDIC SYSTEMS. 4.DETECTABLE CELLULAR OUTPUT SIGNALS. 4.1.Cell Metabolism. 4.2.Cell Morphology. 4.3.Electrical Patterns. 5.CELL MANIPULATION ON CHIPS. 6. CONCLUSIONS AND FUTURE PROSPECTS.- NETWORK ON CHIPS. 1.INTRODUCTION. 2.TECHNICAL ASPECTS AND UNDERLYING ASSUMPTIONS. 2.1.System requirements. 3.ORIGIN OF THE SIGNAL RECORDED. 4.SPATIAL RESOLUTION. 5.LFP AND PLASTICITY. 6.NETWORK DYNAMICS AND EPILEPTIFORM ACTIVITY. 7.DRUG TESTING WITH MEAS. 7.1.Using Network Properties as Endpoints in Drug Assays. 7.2.Assessing Distributions of Neuronal Responses to Dopamine. 7.3.Cardiopharmacology. 8.DATA ANALYSIS. 9.OUTLOOK.- BIONANOSYSTEMS. 1.INTRODUCTION. 2.BASIC CONCEPTS AND EXPERIMENTAL METHODS. 2.1.Self-assembly. 2.2.Optical properties of semiconducting nanocrystals. 2.3.Optical properties of metal nanocrystals. 2.4.Magnetic nanoparticles. 2.5.Conjugation of nanomaterials and biomolecules. 2.6.Bioanalysis with bionanosystems. 2.7.Imaging. 3.APPLICATIONS. 3.1.DNA detection. 3.2.Immunoassays. 3.3.Imaging. 4.CONCLUSION AND OUTLOOK. 5.ACKNOWLEDGEMENTS . 6.REFERENCES.