Why Being Small? Savings in time & cost. Disposable Parallel processing Integration/Automation. Gain from the unique microscopic features
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1 Miniaturization in Electronic Technology ENIAC: the "Electronic Numerical Integrator and Calculator, 1943 ENIAC filled a 20 by 40 feet room, weighed 30 tons, and used more than 18,000 vacuum tubes. iphone 6 A8 Chip, 2014 >10 9 transistor
2 Savings in time & cost Less materials and samples Short processing time Disposable Parallel processing Integration/Automation Gain from the unique microscopic features Laminar Flow Why Being Small? High surface to volume ratio High single-to-noise ratio in transuding signals Small thermal mass Strong fields such as electric fields 2
3 Why Being Small? Length Scale Matching Manipulation of molecules and cells High resolution / sensitivity (Kim) e.g. to facilitate single-molecule diagnostics, study of single-cell biology (Wang) >100 m 1 m 10-2 m 10-6 m 10-9 m Spacecraft Human Organ Tissue Cell DNA Micro/Nano Technology 3
4 Classes of BioMEMS (Bio-MicroElectroMechanicalSystem) Microfluidics & Microfluidic Devices Biosensors and Bioelectronics Neural Interface Devices Chromatography /Electrophoresis Devices Microsurgical Tools Bioreactors Tissue Engineering Devices Molecule /Cell Handling Devices Implantable Devices, Drug Delivery Devices 4
5 Examples of MEMS Devices Micro-mirrors Spider mite on gears (Sandia) 5
6 Examples of Industrial MEMS Devices Air Bag Sensor Bubble Inkjet Projector (Analog Device) (HP) Motion & Orientation sensor (Wii) (Texas Instruments) (Nintendo) 6
7 Apple iphone 6 6-axis Gyro/Accel (Invensense) 3-axis Accelerometer(Bosch) 3-axis Magnetometer (AKM) 3 microphones (Knowles) Pressure Sensors (Bosch) 7
8 MEMS Is Everywhere in Your Daily Life Internet of Things (IoT) Trillions of MEMS sensors coming soon! 8
9 Capillary Electrophoresis 9
10 Micromachined Capillary Electrophoresis (m-ce) 10 High throughput Low volume Rapid analysis Integrated with thermal cycling and CE for Sanger sequencing Off-chip optical detection (Ra Mathies, PNAS 2006)
11 11 Thermal Cycling for Polymerase Chain Reaction (PCR) PCR is an expensive and time-consuming technique
12 12 Continuous-flow Micro PCR Integration of CE and m-pcr (A. Manz, Science 2002) (M.A. Burns U Mich, Science PCR reaction Gel electrophoresis Microfluidics On-line electrical detector
13 Microfluidic Digital PCR : Nanoliter-sized PCR arrays 1176 chamber 6.25 nl each chamber (J.R. Leadbetter, Science 2006) 13
14 Droplet Digital PCR: Picoliter-sized PCR arrays Photon Counts per 100usec Photon Counts per 100usec 2000 Calcein Channel ROX channel Time (sec) 1500 Calcein Channel ROX channel Time (sec) (T. Rane, Lab Chip, 2015) 14
15 Analysis of Single Cells 15 Preparation of a single cell Single-Molecule Detection (R. Zare, Scinece 2006)
16 Laminar Flow-Based Assay 16 T-Sensor Separation (P. Yager) Laminar flow initiate reaction Diffusion-based analysis Rapid Mixing
17 Flied Flow Fraction-DEP cell sorter 17 Field flow fraction using DEP force ( U. Texas, Houston)
18 Free Solution Hydrodynamic Separation
19 Nano Fluidics nm-wide nanochannel array Stretch of l DNA (48.6 kbp)fragment DNA is driven by E-field (R. Austin)
20 20 Digital Microfluidics Pump-free and valve-free Each sample and reagent is individually addressable Array-based analysis
21 Integrated DNA Preparation and PCR Detection Centralized & manual tube based PCR detection Sample In Answer Out Cell lysis DNA purification & concentration PCR reaction DNA amplification (thermal cycling) Lysis/Binding buffer Washing buffer 1 Sample 2 Sample 1 Using Silica Superparamagnetic Particles (SSP) as a solid phase within droplets
22 Surface elevation SSP plug Surface topology assisted SSP and droplet manipulation Drops in Air a) a) Drops in Oil b) SSP plug Surface elevation BioSensing & BioMEMS 530/ Jeff Wang (Y Zhang, Johns Lab Hopkins Chip 2011) University
23 Fluorescence Intensity (AU) Fluorescence Intensity (AU) Fluorescence Intensity (AU) On-Chip Real-Time PCR Detection Normalized Fluorescence Intensity Normalized Fluorescence Intensity -df/dt -df/dt Detection of E coli 16S gene from cell culture bp 250bp 200bp 150bp 100bp Marker Amplicon Cycle (n) a) b) a) b) Detection of Rsf-1 marker from whole blood Fluorescence Fluorescence 0.10 Negative first derivative Negative first derivative BioSensing & BioMEMS 530/ Cycle (n) Temperature Jeff Wang (Celsius) Johns Hopkins University Cycle (n) Temperature (Celsius)
24 Microfluidic Droplet Technology for High-Throughput Analysis Features Monodisperse droplets of sizes ranging from nl-pl High speed droplet generation of > khz Potential applications Low-cost & High throughput screening Biochemical synthesis Digital PCR Single-cell analysis 24
25 Droplet Microfluidics for Monitoring of Kinetics
26 DNA Microarrays 26 Affymetrix Fabricated with lithographic technique cdna array Gene expression profiling Relative fluorescence measurement
27 Neural Probe/ Neuro Implant 27 Neuro-circuit interaction neuro-recoding Prosthesis research Chemical delivery Issues with long term implant bio compatibility
28 28 Tissue Engineering / Cell Patterning Patterning cells using microfluidics Control of microenvironments using microfluidics Single-cell (controlled small number of cells) patterning High-throughput search for right cell conditions for controlling cell growth, differentiation, apoptosis) ( Whitesides)
29 Corneal Microtissue Culture ( C. Puleo, Lab Chip. 2009) 29
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