Lab-on-a-Chip (LOC) Miniaturization on micro- and nanoscale.

Transcription

1 Lab-on-a-Chip (LOC) Miniaturization on micro- and nanoscale downloaded

2 Contents What is a lab on a chip (LOC)? Introduction History Fabrication technologies Applications Biosensor on a LOC Concept of Optical Resonators and Fabrication Biosensing with Optical Microresonators On-chip integration Limitations and challenges of LOC for the future Outlook 2

3 Introduction WHAT IS A LAB-ON-A-CHIP? 3

4 What is a Lab-on-a-chip? 4

5 What is a Lab-on-a-chip? miniaturized laboratory functions onto a chip size of a quarter several experimental steps in one process + automated data analyses minimal sample- and chemical-requirement rapid analysis times reduced waste device which contains micro channels (flow of liquid samples) and integrates measuring and sensing components 5

6 History Lab-on-a-chip history linked to microfluidics Microfluidics linked to microtechnology of semiconductors First real lab-on-a-chip created in 1979 at Stanford University for gas chromatography 80s: LOC major research started with development of microfluidics and the adaption of micro fabrication processes for the production of polymer chips 90s: miniaturization of biochemical operations, focused on cell biology 6 Micro total analysis system (µtas): perform all operations on one chip downloaded

7 Fabrication technologies PDMS lab-ona-chip Silicon lab-ona-chip Thermopolymer lab-on-a-chip Glass lab-on-achip Paper lab-ona-chip reviews-and-tutorials/introduction-to-lab-on-a-chip review-history-and-future/, downloaded

8 LOC Sample delivery - Microfluidics microfluidics: multidisciplinary field intersecting engineering, physics, chemistry, biochemistry, nanotechnology and biotechnology microfluidics is a tool in moving tiny amounts of fluid around biochemical samples in aqueous solutions engineeringtopics/articles/ bioengineering/ usingmicrofluidics-todiagnose-hiv downloaded:

9 Lab-on-a-chip- applications Biochemical assays: real-time PCR, immunoassay, dielectrophoresis for detecting cancer cells and bacteria, etc. Chemical application: separating molecules from mixtures, chemical reactors, chemical detections. etc. Biological application: cell coculture, biosensor, drug screening, single-cell analysis, etc. 9 downloaded:

10 BIOSENSOR ON A LAB-ON-A-CHIP 10

11 On-chip biosensors applications: environmental monitoring, quality control of drinking water, food diagnostics, early stage disease detection: viral detection (e.g. influenza, HIV ) provide: high sensitivity, low detection limits, compactness, real-time measurements optical resonators: interaction of light with matter on nanoscale 11

12 Optical resonator-biosensors resonators: simplest ones: microspheres, planar ring resonator array, cylindrical optical fibers, fiber coils, microdisks, microtoroids exotic structures: bottle-, bubble-microresonator html, downloaded

13 CONCEPT OF OPTICAL MICRORESONATORS 13

14 Concept of optical microresonators Light can be confined in a dialectic medium by total internal reflection Whispering Gallery Modes LAS Microlaser.Dome.jpg, downloaded Research Group of Prof. Dr. Kalt Institute of Applied Physics

15 Whispering Gallery Modes Total internal reflection resonance condition: with downloaded Research Group of Prof. Dr. Kalt Institute of Applied Physics

16 Electric Field - Distribution resonant light circulates evanescent field reaches 10nm-100nm into the surrounding medium, Lasing threshold of active polymer disk resonators - effect of excitation and collection geometry, Bachelorarbeit am Institut für Angewandte Physik Karlsruhe 16

17 Fabrication of goblet-shaped-resonator-arrays 17 low-cost disposables parallel processing substrate: Silicon but arbitrary lift-off resist: thin polymer film resonator material: poly-methylmethacrylate (PMMA) T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: /C5LC00670H (Paper) Lab Chip, 2015, 15,

18 Characterization of resonators Quality factor Q: ratio of resonance wavelength to the full-width-at-half-maximum of resonance dip representing the number of round trips that circulating resonant light can make along the resonator rim Intensity 18

19 Quality factor measurement Transmission Wavelength, Lasing threshold of active polymer disk resonators - effect of excitation and collection geometry, Bachelorarbeit am Institut für Angewandte Physik Karlsruhe 19

20 Losses ideal resonator: infinite Q extern and intrinsic losses 20

21 Effective optical path length photons circulate several thousand times before exiting long optical path length: -> strong light-matter-interaction _Whispering_Gallery_Mode_microresonators_Fundamentals_and_applications, downloaded

22 BIOSENSING WITH OPTICAL MICRORESONATORS 22

23 Biosensing micro- or nano-metric object (bacterium, molecule) in contact with confined circulating light at the resonator surface downloaded

24 Biosensing wavelength-shift interaction of matter with evanescent field of resonator causes a shift in resonant-wavelength and broads the spectral width 24 Shift of resonance wavelength and broadening of line width of a WGM due to adsorption of E.coli bacteria %2F61F98678%2D9E72%2D7682%2D F07670D6%5F148405%2Foe%2D15%2D25%2D17410%2Epdf%3Fda%3D1%26id %3D148405%26seq%3D0%26mobile%3Dno&org=, downloaded

25 Calculation of spectral shift Heuristic approach: j a_ex: polarizability ~ molecular weight, : surface density of molecules forming a layer complete calculation: shifts reflect refractive index changes down to RIU sensitivity up to 1pg/mm 2 25

26 Functionalization for biosensing requirements: selectivity, sensitivity, stability and reversibility surface coating Silvia Sorio, Optical Microspherical Resonators for Biomedical Sensing, Sensors 2011, 11, ; doi: /s , downloaded

27 On-Chip Integration planar resonators: phase-matched evanescent coupling with tapered fiber requirements: relative positioning of fiber and resonator in sub-micrometre precision downloaded

28 On-Chip Integration alternative: active resonator doping with laser dye molecules -> optically pumped and probed via free-space optics downloaded

29 Free-space setup for doped resonators 29 need of nanotechnology for the spectrometer T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: /C5LC00670H (Paper) Lab Chip, 2015, 15,

30 On-Chip integration of 3D-resonators resonator array integrated into a state-of-art microfluidic chip T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: /C5LC00670H (Paper) Lab Chip, 2015, 15,

31 Sensing capability determine the bulk refractive index sensitivity (BRIS) series of 5 solutions with refractive indexes from 1,3329 to 1,3355 T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: /C5LC00670H (Paper) Lab Chip, 2015, 15, sensitivity:10.56 nm/riu 31 T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: /C5LC00670H (Paper) Lab Chip, 2015, 15,

32 LIMITATIONS AND CHALLENGES OF LOC FOR THE FUTURE 32

33 Limitations and Challenges of lab-on-a chip signal/noise ratio from miniaturization need of external system to work current challenges: industrialization for commercialization (fabrication processes, design of specific surface treatments, flow control system ) increase of maximum number of biological operations integrated on the same chip 33

34 LOC outlook already commercialized: glucose monitoring or HIV detection and heart attack diagnostics near future: LOC widely used in hospitals later: real time monitoring of health at home in developing countries LOC enables diagnostics Change of our daily live for wider population -> change of daily lives Change of our daily live 34 downloaded

35 Sources Annu. Rev. Fluid Mech : Downloaded from ENGINEERING FLOWS IN SMALL DEVICES: Microfluidics Toward a Lab-on-a-Chip Philip S. et. al, Detection of prostate specific antigen with nanomechanical resonators 2009, DOI: /b907309b Kristinn B. Gylfason, Integrated Optical Slot-Waveguide Ring Resonator Sensor Arrays for Lab-on-Chip Applications KTH - Royal Institute of Technology, Stockholm, Sweden,2010 Daniel Hill, Nanophotonic Biosensor Technologies for Lab on Chip Applications a Focus Article on Optical Biosensors from Three EC Lab on Chip Projects with a Comparison to the State of Art, Springer Science+Business Media New York 2014 Silvia Sorio, Optical Microspherical Resonators for Biomedical Sensing, Sensors 2011, 11, ; doi: /s Yuze Sun, Optical ring resonators for biochemical and chemical sensing, Anal Bioanal Chem (2011) 399: DOI /s z T. Wienhold, All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers, DOI: / C5LC00670H (Paper) Lab Chip, 2015, 15, , Lasing threshold of active polymer disk resonators - effect of excitation and collection geometry, Bachelorarbeit am Institut für Angewandte Physik Karlsruhe 35