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BEC2010 Tallinn, Estonia October 4-6, 2010 Usage of microfluidic lab-on-chips in biomedicine Res. Eng. Athanasios Giannitsis Professor Mart Min 1 What are the microfluidic lab-on-chips? Lab-on-chips : A class of submillimetre size bioanalytical devices. Perform: fluidic processes, sensing, analysis and separation of biochemical samples. Integrate: fluidics, electronics, optics and biosensors. Analyse: metabolites, molecules, proteins, nucleic acids, cells and viruses. 2 Subsets and supersets of lab-on-chips MEMS (MicroElectroMechanical Systems) Embedded systems Microfluidic lab-on-chips devices μ-TAS Biosensors Implantable devices 3 Application areas of lab-on-chip devices Diagnostics Biochemistry Bioanalysis Drug tests Cytometry Cell biology Genomics & proteomics Water & food quality Environmental monitoring Biosensing Biotechnology Biocomputing Pharmaceutics 4 Technical advantages of lab-on-chips Portability Low power consumption Modularity Straightforward integration Reconfigurability Embedded computing Automated sample handling Low electronic noise Few moving or spinning components 5 Operational advantages of lab-on-chips Automate laboratory processes like sample transport, dispensing and mixing. Highly reduce the time of laboratory tests. Require tiny amounts of sample and reagents. High reduction of contaminants due to chip sealing and environmental isolation. Support continuous and segmented flow. Accelerate chemical reactions due to the use of tiny samples. Obtainable temperature homogeneity due to tiny fluidic volumes. Relatively high throughput processing. 6 Production advantages of lab-on-chips Affordable mass production. Affordable replacement cost. Relatively short development times. Short quality tests times. Require existing commercial computer aided design software. Require existing commercial modelling software. 7 Clinical assessments that lab-on-chip devices are capable for Drug tests Nucleic acid amplification Cytometry and cell analysis Genenetic mapping(genomics) Electroporation Enzymatic assays Blood tests Peptide analysis Cytotoxicity studies Protein analysis (proteomics) Bioassays 8 Electric actuation methods Piezoelectric Electrocapillary Capillary electrophoresis Electrowetting Electroosmosis / streaming potential Electrophoresis Dielectrophoresis 9 Detection methods Bioimpedance spectroscopy Capacitance sensing Voltametry Dielectrophoresis & rotational spectra Fluorescence & image processing 10 Types of microfluidic lab-on-chips Micropumps & microvalves Bioimpedance chips Fluidic mixers Electroporation chips Droplet generator chips Microbioreactors Electrowetting chips Cytometers Electrophoretic chips Dielectrophoretic chips Polymerase chain reaction (PCR) chips Immunoassay chips Microarrays Magnetophoretic chips 11 Microvalves Closed Open Elastomer pressurisation decompression Electroactive elastomers and piezoelectric films can be used as control membranes 12 Mixers T-junction fluidic mixer Increase of mixing 13 Droplet generators Cross-junction droplet generator T-junction droplet generator 14 Electrowetting chips Ground 15 Capillary electrophoresis chips V2 Outlet of main flow separation channel collection outlet Inlet of main flow V1 (high voltage pulses) 16 Dielectrophoretic chips Cells collected at electrodes Cells directed away from electrodes 17 Magnetophoretic chips coils The magnetic fluid is moving forwards due to the action of the magnetic force Pipe diameter Magnetic strength Ferrofluid type Surfactant 0.004 m 300 Gauss oil based hydrophobic 18 Bioimpedance chips Bioimpedance is capable of sensing cells or nanoparticles 19 Optical cytometers Image acquisition Cytometry analysis Fluorescent image acquisition via microscopy 20 Polymerase chain reaction chips PCR chips provide temperature homogeneity and reaction conditions inlet PCR requires three thermal cycles: Denaturation step at 90-95oC for 20-30 seconds Annealing step at 50-60oC for 20-40 seconds Elongation step at 60-70oC for 5-15 minutes 21 Microarrays Cellular microarray: examines cells reaction with antibodies proteins or lipids. DNA microarray: detects DNA / RNA, and gene expression. Protein microarray: detects proteins in liquids, protein to protein interactions, biomolecules. Antibody microarray: detects antigens, biomarkers, and protein expressions. Chemical microarray: detects proteins that bind on specific chemical compounds. Fluorescence mapping 22 Electronic circuitry on lab-on-chips Analog front-end Analog-digital converter ADC Digital signal processor Sensor Signal Conditioning Front-end Memories ADC Digital Signal Processor Bus 23 Analog Front-end Input Output Low signal amplitude Low frequency noise Volt level output for subsequent ADC Low noise Cross-parameter stability Cross-parameter sensitivity Sensor mV (mΩ, fF) Amplifier V 24 Future trends in lab-on-chip technology Technical improvements Improvement in reliability Improvements in portability Parallel sample processing Ultralow power consumption Smaller and lighter devices Wireless networking Advance user interfaces Standalone computing Standardisation of fabrication materials Biocompatibility improvements Nanoscale channels development Usage benefits Personalised medicine Point-of-care diagnostics Marine sensors Monitor pollution Monitor pandemics / diseases Link to medical and patient databases Usage as terminal testers Telemedicine Military medicine BEC2010 Tallinn, Estonia October 4-6, 2010 25