P. Bienstman, E. Hallynck, C. Lerma Acre, S. Werquin, J.- W. Hoste, D. Martens PHOTONICS RESEARCH GROUP 1

Transcription

1 PHOTONICS RESEARCH GROUP P. Bienstman, E. Hallynck, C. Lerma Acre, S. Werquin, J.- W. Hoste, D. Martens PHOTONICS RESEARCH GROUP 1

2 Overview Silicon nanophotonics biosensors Applications: Conformational analysis Tuberculosis detection Packaging platforms: Through-chip fluidics Combining chips with reaction tubes Chip-on-fibre PHOTONICS RESEARCH GROUP 2

3 SILICON NANOPHOTONICS BIOSENSORS PHOTONICS RESEARCH GROUP 3

4 Silicon Photonics: optical chips intel transistor radio discrete elements 1954 pentium nanoelectronics discrete elements 2009 product photonic IC Silicon nano photonic IC 2009 research PHOTONICS RESEARCH GROUP 4

5 Silicon Photonics: Optical Integrated Circuits PHOTONICS RESEARCH GROUP 5

6 Normalized tansmission [db] Silicon Photonics: example Integrated spectrometer Hair at same scale 250 m 0 0 FSR=25.3nm 450 nm Transmission [db] Design/fabrication by Ghent University + IMEC wavelength [µm] 4 5 PHOTONICS RESEARCH GROUP wavelength [nm]

7 Intensiteit [A.U.] Golflengte [nm] Verschuiving [nm] Ring resonator biosensor Wavelength shift Time trace binding buffer level resonance wavelength shift [nm] Concentration measurement Wavelength Golflengte [nm] Time avidin concentration [μg/ml] Concentration [ug/ml] PHOTONICS RESEARCH GROUP 7

8 Nanophotonics biosensing platform Silicon-based Cheap, CMOS mass fabrication Hundreds of ring sensors on single chip Label-free Both proteins and DNA 8 PHOTONICS RESEARCH GROUP 8

9 TE/TM BIOSENSOR PHOTONICS RESEARCH GROUP 9

10 Problem Interest in measuring conformational changes: Don t want to rely on assumptions like total bound mass. Need way to disentangle thickness and refractive index. PHOTONICS RESEARCH GROUP 10

11 Dual polarisation ring 2 measurements (TE + TM) determine 2 unknowns (d + n) PHOTONICS RESEARCH GROUP 11

12 For more details: Determination of thickness and density of a wet multilayer polymer system with sub-nanometer resolution by means of dual polarization silicon-on-insulator microring Jan-Willem F. I. B. Hoste, Bruno G. De Geest, Peter Bienstman 12 February :40-3:00 PM Part of SPIE BiOS PHOTONICS RESEARCH GROUP 12

13 TUBERCULOSIS DETECTION PHOTONICS RESEARCH GROUP 13

14 The need 8.8 million new TB cases per year 5000 people dying each day 1/3 of people have latent TB Diagnostic tests exist, but are either expensive or not sensitive enough PHOTONICS RESEARCH GROUP 14

15 Pocket project Detection of TB biomarkers in urine SiN platform in visible: cheaper sources and detectors Cheap readout: broadband source + MZI + AWG Novel selective Ab cocktail PHOTONICS RESEARCH GROUP 15

16 Bulk shift Peak Wavelength shift (nm) Peak shift = *Index difference ,0005 0,001 0,0015 0,002 0,0025 Index difference of analyte with water (RIU) LoD for unoptimised device: 7 10^-6 PHOTONICS RESEARCH GROUP 16

17 Binding curves No specific A OFF No specific A ON HCl ON HCl OFF HCl ON HCl OFF HCl ON Water ON Water OFF specific B ON specific B OFF specific B ON specific B OFF specific B ON specific B OFF PHOTONICS RESEARCH GROUP 17

18 THROUGH-CHIP FLUIDICS PHOTONICS RESEARCH GROUP 18

19 One of the major issues in biosensors is analyte delivery Pure diffusion is too slow Introducing laminar flow improves delivery time, however Laminar flow velocity near sensor 0 Diffusion-dominated region Problem for low concentrations PHOTONICS RESEARCH GROUP 19

20 Alternative: flow-through sensor Droplet containing molecules is applied on a sensor. Sensor = membrane with holes (radius >> molecules) By applying under- and overpressure, droplet is pulled or pushed through, along with biomolecules. Cycle can be repeated until most biomolecules have bonded in holes. PHOTONICS RESEARCH GROUP 20

21 Related ideas Continuous flow through a photonic crystal (still with flow channel) Same concept, different scale, no photonics PamGene (Huang et al, Optics Express, 17(26): ) PHOTONICS RESEARCH GROUP 21

22 What transducer to use? Type Mechanics Photonics Photonic crystal + -- Mach-Zehnder interferometer - ++ Due to a non-uniformity in vapour HF process, we obtained a mechanically robust Mach-Zehnder interferometer PHOTONICS RESEARCH GROUP 22

23 Fabrication in Silicon-on-Insulator Mass-producability of SOI is major advantage for biosensors and should be maintained in fabrication of membranes Substrate can be wet etched anisotropically using KOH Silicon dioxide is removed with vapour HF PHOTONICS RESEARCH GROUP 23

24 Silicon substrate etch using KOH Etching mask: 400 nm PECVD Si 3 N 4 on 400 nm PECVD SiO 2 Lithography is performed on back side using alignment markers on top side We open windows in the nitride/oxide mask using RIE An extra protective coating is applied on the top side due to pinholes in nitride ProTEK (Brewer Science) PHOTONICS RESEARCH GROUP 24

25 Silicon substrate etch using KOH 15 mm (.6 ) 10 mm (.4 ) PHOTONICS RESEARCH GROUP 25

26 Silicon substrate etch using KOH 40 µm 60 µm PHOTONICS RESEARCH GROUP 26

27 Silicon substrate etch using KOH PHOTONICS RESEARCH GROUP 27

28 And finish with a dash of HF ProTEK layer is removed Sample is put in HF solution where top nitride and oxide layers and buried oxide (BOX) layer will be etched PHOTONICS RESEARCH GROUP 28

29 And finish with a dash of HF PHOTONICS RESEARCH GROUP 29

30 Vapour HF is a must PHOTONICS RESEARCH GROUP 30

31 Pressure needed to pull a droplet through? Initial equilibrium We provide a hydrophilic material, surface tension does the rest (hydrophobic pressure of over 4 bar required) Creating a flow Membrane can be modelled as parallel channels Using COMSOL, the flow rate in function of the pressure can be calculated 10 kpa: MZI = 2.7 µl/s; PhC = 0.01 µl/s PHOTONICS RESEARCH GROUP 31

32 Through-chip flow PHOTONICS RESEARCH GROUP 32

33 Measurement set-up PHOTONICS RESEARCH GROUP 33

34 Applying pressure PHOTONICS RESEARCH GROUP 34

35 Proof-of-principle: BSA (0.625 mg/ml) Flow-through at least 3 times faster than in the case of no pumping PHOTONICS RESEARCH GROUP 35

36 COMBINING CHIPS WITH REACTION TUBES PHOTONICS RESEARCH GROUP 36

37 Costs Time Labeled biosensing ELISA Bioassays Sample Preparation Incubation Rinse PHOTONICS RESEARCH GROUP 37

38 LABEL-FREE BIOSENSING Disposable LABELED format Commonly BIOSENSING used in hospitals and labs Compatible with any kind of fluid handling system Avoids costs and complexity of labels Quantitative information High throughput Real time response Interactions can be monitored continuously Kinetics information Concentration PHOTONICS RESEARCH GROUP 38

39 Optical transducer at the bottom of the reaction tube PHOTONICS RESEARCH footer GROUP 39 39

40 Problem to be solved The transducer chip in reaction tube needs flow to be able to work in label-free regime Microfluidics analyte Continuous flow Microchannels Efficient transport of Fast and precise PHOTONICS RESEARCH GROUP 40

41 Perforations through the chip 40 µm Laser ablation. A Duetto laser source The dimensions and the position to be optimized 1000 ps-duration pulses were applied with a repetition rate of 50kHz at 355nm. PHOTONICS RESEARCH GROUP 41

42 Ring resonator biosensors b ) Fluid flows through the perforations Perforations through the chip PHOTONICS RESEARCH GROUP 42

43 Diffusion µm The analyte is efficiently transported to a distance of a few micrometers from the sensor surface. Fluid flows through the perforations Diffusion µm PHOTONICS RESEARCH GROUP 43

44 Setup The sample is fixed by means of vacuum Pump Vacuum Negative pressure: the fluid on the chip is sucked. Positive pressure: the fluid previously sucked is pushed up again increasing like this the interaction of this fluid with the sensors. PHOTONICS RESEARCH GROUP 44

45 Setup Light is coupled in and out from the bottom of the chip. PHOTONICS RESEARCH GROUP 45

46 Optical setup Input grating coupler SOI Substrate Output grating coupler Measuring Collimator through the Tunable laser ~1550nm IR Camera Si substrate PHOTONICS RESEARCH GROUP 46

47 3 STEPS: 1. Silanization of the surface with APTES 2% Small volumes of the different solutions were pippeted in the cuvette and sucked through the holes of the SOI chip. Ethanol APTES SOI PHOTONICS RESEARCH GROUP 47

48 3 STEPS: 2. Binding of the Biotin 3mg/ml in PBS ph 7 Small volumes of the different solutions were pippeted in the cuvette and sucked through the holes of the SOI chip. Biotin PBS SOI PHOTONICS RESEARCH GROUP 48

49 3 STEPS: 3. Binding of Streptavidin 0.1ml/ml in PBS ph 7. Small volumes of the different solutions were pippeted in the cuvette and sucked through the holes of the SOI chip. Streptavidin PBS SOI PHOTONICS RESEARCH GROUP 49

50 CHIP-ON-FIBRE PHOTONICS RESEARCH GROUP 50

51 DESING: SENSOR ON FIBER Development of a fiber probe sensor for use as a biosensor It is transferred from the silicon-on-insulator chip onto the fiber facet. PHOTONICS RESEARCH GROUP 51

52 DESIGN: SENSOR ON FIBER PHOTONICS RESEARCH GROUP 52

53 FABRICATION SOI: 220nm Si 2µm SiO 2 750µm Si Dry etching: 2µm SiO 2 layer thinned down to 700nm PHOTONICS RESEARCH GROUP 53

54 FABRICATION Wax Si Wafer PHOTONICS RESEARCH GROUP 54

55 FABRICATION Si substrate removed 1. Mechanical grinding 2. Dry etching 3. Wet etching PHOTONICS RESEARCH GROUP 55

56 FABRICATION PHOTONICS RESEARCH GROUP 56

57 FABRICATION PHOTONICS RESEARCH GROUP 57

58 FABRICATION 2010 PHOTONICS RESEARCH GROUP 58

59 Wavelength Shift (nm) No degradation of sensitivity compared to normal ring resonators Bulk sensing experiments: Sensitivity for refractive index change in aqueous ethanol solutions 2 1,6 x Measurements Fitting 1,2 ~70 nm/riu 0,8 0,4 0 1,33 1,335 1,34 1,345 1,35 1,355 1,36 1,365 Refractive Index Unit (RIU) PHOTONICS RESEARCH GROUP 59

60 Acknowledgements UGent Tom Claes Elewout Hallynck Cristina Lerma Arce Sam Werquin Jan-Willem Hoste Daan Martens Pocket partners L. Lechuga et al. (CSIC) M. Singh et al. (Lionex) L. Lagae et al. (imec) H. Becker et al. (MFCS) R. Bockstaele et al. (Trinean) PHOTONICS RESEARCH GROUP 60

61 INTEGRATION WITH DIGITAL MICROFLUIDICS PHOTONICS RESEARCH GROUP 61

62 Microfluidics used in Silicon Photonics PDMS microchannels fabrication Packaging Tubing connections Leaks Bad adhesion PHOTONICS RESEARCH GROUP 62

63 MeBioS Biosensors KU Leuven PHOTONICS RESEARCH GROUP 63

64 Electrowetting-on-dielectric A potential is applied between a conducting liquid and an electrode modifying the surface tension hydrophobic hydrophilic Charge accumulates at the solid-liquid interface, leading to a change in contact angle PHOTONICS RESEARCH GROUP 64

65 Digital Microfluidics Tape spacer Aluminium layer pattern by standard photolithographic techniques. MeBioS Biosensors KU Leuven PHOTONICS RESEARCH GROUP 65

66 Combining both technologies Array of ring resonators SOI SOI Teflon coating PHOTONICS RESEARCH GROUP 66

67 Optical setup IR Camera Tunable laser ~1550nm Measuring Collimator through the Si substrate PHOTONICS RESEARCH GROUP 67

68 PHOTONICS RESEARCH GROUP Sensors area PHOTONICS RESEARCH GROUP 68

69 Resonance wavelength shift vs. Time Measured in water and two different salt solution Water concentrations Salt 1 Water Salt 2 PHOTONICS RESEARCH GROUP 69

70 Results Resonance wavelength shift Refractive Index Unit vs. Y=77*x-1e +002 PHOTONICS RESEARCH GROUP 70

71 Acknowledgements UGent Tom Claes Elewout Hallynck Cristina Lerma Arce Sam Werquin Jan-Willem Hoste Daan Martens Pocket partners L. Lechuga et al. (CSIC) M. Singh et al. (Lionex) L. Lagae et al. (imec) H. Becker et al. (MFCS) R. Bockstaele et al. (Trinean) PHOTONICS RESEARCH GROUP 71