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Microfluidics & The Field of Bioengineering What is Bioengineering? • Engineering emphasizes applications in science • Engineering focuses on the design of more efficient, cost effective, new, and better tools and processes Bioengineering • Bioengineering combines life sciences with engineering design to produce new, more efficient devices for use in many areas – Diagnostic tests for disease (microchips) – Environmental monitoring (biosensors) – Medical devices/machinery (prosthetics) – Military applications (sensors in fabric to monitor soldiers, improved camouflage) – Biomimetrics (applying biology concepts to artificial systems) Microfluidics: Computer Revolution Analogy How did this happen? Semiconductor Microelectronics: Shrinking transistors, higher densities Electrons behave the same on the microscale as they do in big wires. Transistor: Electron Routing What is microfluidics? Major Difference: for fluids, the fundamental physical behavior changes rapidly as the size scale is decreased. Microfluidics: Fluid Routing ? What is microfluidics? Understanding microfluidic behavior requires knowledge of math, physics, chemistry & engineering. To name a few: Fluid mechanics: How do fluids behave on a small scale? Electrostatics: What is the importance of electricity, magnetism & charged particles ? Materials Science: What are the best materials for making microfluidic devices? Small dimensions cause some physical phenomena that we often neglect to become very important. Microscales Strand of human hair 10 mm Microchannel Caliper Life Sciences What is microfluidics? Essentially dedicated to miniaturized plumbing & fluid manipulation Offers the possibility of solving outstanding issues for biology Enabling fluid automation to save time, increase efficiency and rival electronic integrated circuits GETTING PUMPED: Just the thing for getting a global view of how a cell works What is a Microfluidic Chip? • made of silicon (PDMS) • pattern is engraved into chip • inlet channels are punched into the silicon • it is attached to glass to form closed channels • fluids can flow through the channels and interact according to the chip design • http://youtu.be/JIewub-bPKY • http://youtu.be/wm2JOuA8K1w What are the Advantages of Microfluidic Chips? • Cost effective • Less hazardous materials generated/used • Sample collection is easier/less painful for the patient • More time efficient diagnostic tests • Portable for use in outdoor settings/areas without power supply needed for big machinery Digital Microfluidics: Bubble Logic Instead of test tubes, chemical reactions can be also performed in droplets. But how do we mix reagents in droplets? • Mixing in a straight channel [video] • Mixing in a serpentine channel [video] Prakash and Gershenfeld. “Microfluidic Bubble Logic,” Science 315: 832-835 , 2007. Lung-on-a-Chip Biomimetic microsystem reproduces functionality of lung alveoli without need for lab animal models for drug screening & toxicity studies. Huh et al. “Reconstituting organ-level lung functions on a chip, “ Science 328: 1662-1668, 2010. Ingber lab at Harvard, Dan Huh Lab-on-a-Chip Micro Total Analysis Systems (µTAS) Protein analysis DNA techniques Drug efficacy studies Single cell analysis Diagnostics, sensors [Burns, M.A. et al. "An Integrated Nanoliter DNA Analysis Device," Science 282: 484-487, 1998.] Most importantly, integration of all components on one device! A Rapid Diagnostic Device One step diagnostic from IBM Zurich: [Video] Readout Making Microfluidic Devices: PDMS Poly(dimethylsiloxane) aka PDMS ≈ Jello for bioengineers! UV light ① Make a mold via photolithography ② Put in the PDMS precursor ③ Bake to cure ④ Assemble microfluidic layers! Source [NBTC: Nanobiotechnology Center - Cornell University] Mask How do you make a MF Chip? 1. Selecting channel shapes from the AutoCad generated master 2. Pour PDMS slowly over the master MF Chip Fabrication (con’t.) 3. Put on hot plate in order to get rid of bubbles in the PDMS 4. Cut out chip from mold, punch inlet channels,& mount on glass slide Additional/supplemental slides Denisin - UC Berkeley What do microfluidic tools give us? Thorsen et al., Science, 2002 What is bioengineering? Designing and creating innovative technologies to advance medicine & clinical research Computational biology determines structure-function relationships of proteins, the workhorses of our bodies Hemoglobin model above Regenerative medicine biodegradable mold seeded with human bladder cells “Lab on a Chip" sequence large genomes quickly and cost-effectively AbioCor Artificial Heart Microfluidic Devices Rapid analysis of samples using: small volumes (μl 10-6 L) high sensitivity & specificity fast response time – minutes small device, portable low energy consumption real-time detection capabilities Applications are broad: rapid medical diagnostics, environmental monitoring, detection of biothreats, basic research… Thought Experiment #1: Does static electricity have more of an effect in moving large or small objects? Why is this true? Feynman, 1960 Thought Experiment #2: What would it be like to swim in a pool full of honey? How would it be different from swimming in water? Why? Feynman, 1960 Molecular Diffusion Thermal motion of particles from an area of high to low concentration to result in gradual mixing tea diffusing into hot water Diffusion rate depends on: fluid temperature & viscosity size (mass) of the particles