Origin of Universe and Ourselves by J1Yab4B


									   Exploring the Origin of
 Life and Consciousness by
Ultra high-speed Microscopes

         Katsushi Arisaka

     University of California, Los Angeles
    Department of Physics and Astronomy
            Katsushi Arisaka’s Research
  Particle Physics:       1880 – now
       Neutrino Physics – Kamiokande           (Japan)
       Cosmic Rays      – Pierre-Auger         (Argentina)
       Dark Matter      – XENON                (Italy)
       LHC              – CMS                  (Switzerland)

  Biophysics:             2006 – now
       Ultra high-speed optical microscopes
       Neurophysics

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         Seven Phases of Cosmic Evolution
 Spontaneous Symmetry Breaking

14 billion years ago

Origin of          Origin of         Origin of      Origin of
Particles          Structure            Life      Consciousness
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            Brain                                           Universe

            100 Billions Neurons                       100 Billions Galaxies

9/11/2012                          Katsushi Arisaka, UCLA         New York Times 8/21/2006
9/11/2012   Katsushi Arisaka, UCLA
                                     Why are we here?
            Unification of Forces (1980)

                                                       Plank Epoch

               100 GeV                      1016 GeV   1019 GeV

                                             1029         1032

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         Hubble Deep Field
  Physicists’ View of Early Universe

                             Fiat lux
                Let there be light
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                Symmetry Breaking
     1B years      Simple
     4                                              b +
     5                                           s µ- W 
                          Symmetry             e + o d -c
     6                                        d e+ Z  -e
                         Break Down            u u µ e
     8                                         b µ W+µ+c
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         Seven Phases of Cosmic Evolution
 Spontaneous Symmetry Breaking

14 billion years ago

Origin of
 3/13/2007             Katsushi Arisaka     9
            CERN and LHC in Geneva

                                            27km Circumference
                                                7+7=14 TeV

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    Sept 15, 2008

 End-cap Muon
made at Westwood
  in 1999 - 2005

                    Katsushi Arisaka, UCLA
         Seven Phases of Cosmic Evolution
 Spontaneous Symmetry Breaking

14 billion years ago

Origin of          Origin of
Particles          Structure
 3/13/2007                     Katsushi Arisaka   12
9/11/2012   13
            New QUPID (Production Version)

                                                                   Photo Cathode (-6 kV)
            Photo Cathode             Quartz
               (-6 kV)

                   Al coating

                 APD (0 V)
                                                                    APD (0 V)


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                               Quantum Efficiency (QHA63, 64)

                         45                                                                   QHA63
Quantum Efficiency [%]




                         20                Xenon



                               100   150   200     250    300      350     400    450   500    550    600
                                                           Wavelength [nm]

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     MAX+LZD = G3 Detector (at DUSEL, ~$100M)

                           70 ton
        20 ton
       (10 ton)           (50 ton)


   3” QUPID x 595 (Top)
      3” QUPID x 595
         (Bottom)              3” QUPID x 2644 (Top)
                             3” QUPID x 2644 (Bottom)

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            90% CL Limits of SI Cross Section




                                       Ar 5ton       G2
                             Xe 1ton
                                       Ar 50ton      G3
                       Xe 10ton

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            Origin of Life

9/11/2012      Katsushi Arisaka,UCLA   18
         Seven Phases of Cosmic Evolution
 Spontaneous Symmetry Breaking

14 billion years ago

Origin of          Origin of         Origin of
Particles          Structure            Life
 3/13/2007                     Katsushi Arisaka   19
            Single Molecule Imaging
January 2006                                            Shimon Weiss (Chemistry)

                                                    It will permit to
              The H33D                                     Nano Technology
                                                   track multicolor
               detector                               qdot-labeled
            attaches to a                           proteins in live
               standard                              cells virtually
            fluorescence                          background-free

                            Particle Physics

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How to observe the Life and Consciousness ?

     We must look for “Live Life”

     Exactly the same way as we look for
       the “Origin of Universe”
            Telescope  Microscope

     Take advantages of the state of art
       “Photon Detectors” in particle physics.
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    Principle of High-speed Bio Imaging
                 Wide Field                      Confocal

        Sample                       Sample


   CCD + FADC (10 – 50 MHz)                 PMT + FADC (10 – 50 MHz)

CMOS [ FADC (50 MHz) * 100 ]             [ HAPD + FADC (1 GHz) ] * 64
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Gold nano particle (40nm) attached to Transferrin Receptor (TfR)
                        on Cancer Cell
                            Manuel Penichet (Oncology), John Miao (Physics)

                                                       10,000 frame/sec
                   Campus-wide Collaborations
                   on High-Speed Bio-imaging

                                                             Dept. of Physics & Astronomy
                                                             (Dolores Bozovic, John Miao,
                                                                     Mayank Mehta)

                                                              Dept. of Electrical Engineering
                                                                      (Bahram Jalali)

  Industrial Partners
(Hamamatsu Photonics,                                    Dept. of Chemistry & Biochemistry
    Photron, Leica)                                                (Shimon Weiss)

                                                          California Nano Systems Institute
                                                              (CNSI, Laurent Bentolila)

                                                        Dept. of Surgical Oncology
                                                            (Manuel Penichet)

                                                       Dept. of Neurology & Neurobiology
                                                             (Carlos Portera-Cailliau,
                                                    Jack Feldman, Tom Otis, Andrew Charles)

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     User-shared Core Facility
of High-speed Microscopes at CNSI

       4D Nano Biophysics
        Image Intensified CMOS Camera
                       MCP                            CMOS Camera
               (Micro Channel Plate)                (> 1,000 frame/sec)
    GaAsP Photocathode
        (50% QE)


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  High-speed Confocal Microscope with ICMOS at CNSI
                                       (1,000 frame/s)

             ICMOS Camera
            (Photron SV200i)

                                                       Leica Microscope

                                 Confocal Spinner
       EMCCD Camera             (Yokogawa CSU-X1)
       (Ando iXon 897)                                           Laurent Bentolila (CNSI)
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                           6D Bio-Imaging
   Ideally observation of Live cells requires the detection
    of photon intensity ( I ) in 6 dimension: I (x, y, z, , , T)
       •    x:
       •    y:
       •    z: Location in depth
       •    : Wave length of emitted photons
       •    : Time delay of emitted photons after excitation
       •    T: Frame rate.
   Photo-detectors have lower dimension:
       • PMT: I(T)                at 50 MHz
       • CCD: I(x, y, T)          at 30 Hz
       • CMOS:                    I(x, y, T) at 5 kHz
   Therefore, “compactification of extra dimension” is

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        E2V-Caeleste scientific CMOS

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   Inventions reported to the UCLA IP Office

  UCLA Case No.                               Invention Title

      2011-119    6D Optical Microscope

      2011-120    5D Imaging Flow Cytometer

      2011-121    GHz Photon Digitizer For Laser Scanning Optical Microscopy

      2011-122    Streak-CMOS 6D Optical Microscope

      2011-123    Super-PIAS Photon Counting Camera
                  Spatio-Temporal Multiplexing (STEM) Microscope System For Multi-
                  photon Imaging

      2011-125    Deep-Tissue Multi-photon Single Molecule Super-Resolution Imaging

      2011-126    A Random Access Axial Focuser For Laser Scanning Imaging

             A new company “Korlin Inc.” has been formed.
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              Origin of

9/11/2012       Katsushi Arisaka   31
         Seven Phases of Cosmic Evolution
 Spontaneous Symmetry Breaking

14 billion years ago

Origin of          Origin of         Origin of      Origin of
Particles          Structure            Life      Consciousness
 3/13/2007                     Katsushi Arisaka                   32
Spatio-Temporal Excitation-Emission Multiplexing
              (STEM) Microscope
             80 MHz                     Adrian Cheng (Physics)
          (100 fs pulse)

  4 Beams
240 frame/sec
                            0 ns
                           +3 ns
                           +6 ns
                           +9 ns

          1 kHz

                               16 kHz
    HAPD #1

     HAPD #2
    150 μm deep

                      Adrian Cheng

3D Structure of     Tiago Goncalves,
 Barrel Cortex      Peyman Golshani,
   of Mouse       Carlos Portera-Cailliau
              In vivo calcium imaging with STEM

                                                  Beam 1
Barrel Cortex                                      (0 ns)

  Layer 2/3

150 μm deep                                       Beam 2
                                                  (+3 ns)

  240 fps
 Raw Data                                         Beam 3
                                                  (+6 ns)

 (x3 faster
 than real)
                                                  Beam 4
                                                  (+9 ns)

                              300 μm
               In vivo calcium imaging with STEM

 Barrel Cortex
   Layer 2/3

 150 μm deep

After averaging

  (x3 faster                                       58 neurons
  than real)
                                                   in our brain)

                               300 μm
How can we recognize
and memorize the space?
Mayank Mehta (Physics, Neurology)

Activity of (excitatory) pyramidal neurons in CA1
       depends on rat’s position: place cells
                           Mayank Mehta (Physics, Neurology)

            Hippocampus has a cognitive map of space
Symmetry breaking as a result of learning

                                      after learning


                                     before learning

   Virtual Reality Experiment on Awake Rats


                                                  Daniel Aharoni
                                                  Bernard Willers
                                                  Mayank Mehta

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               Four Major Science

   Origin of Particles                   Origin of Universe
     Particle Physics                             Cosmology

        Origin of Life                        Origin of
   Molecular Biology

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     Future of Ultra High-speed Bio Imaging

 Origin of Life:
    Networks of molecules in/on a cell
    Competition against Brownian : 10 – 100 nm / 1 msec
 Origin of Consciousness:
    Neural networks
    Action potentials: 1 msec

 > 1,000 frame/sec with nano second time stamp.
    6D Bio Imaging

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                                                              Other Senior                                  High-speed
  Scientific Objectives     Department         Prime PI                        Grad Students     Sample                       Funding      Activities
                                                                Person                                      Microscopes
                            Physics &                                                                                          Keck
 Neurophysics (Virtual                                                         Daniel Aharoni,
                            Astronomy,      Mayank Mehta                                           Rat      2PE, Tetrode     Foundation    2009 - Now
       Reality)                                                                Bernard Willers
                            Neurology                                                                                         pending
                            Physics &          Dolores
    Hair cell motion                                                           Lea Fredrickson     Frog        CMOS           NSF MRI      2007 - Now
                            Astronomy          Bozovic
                            Physics &          Katsushi       Luis Beltran-
   Neutral Networks                                                             Adrian Cheng     Zebrafish 2PE, Conforcal     NSF MRI      2008 - 2009
                            Astronomy          Arisaka          Parrazal
                                                           Xavier Michalet,                                   64ch FCS,
    Single Molecule          Chemistry      Shimon Weiss                       Daniel Aharoni      Cells                      NIH R01      2006 - Now
                                                            Ryan Colyer                                         ALEX
                                               Manuel         Gustavo
 TfR tracking on Cancer Oncology, Physics &                                                                                   (NSF MRI
                                            Penichet, John Helguera, Jose                          Cells    CMOS, ICMOS                    2007 - Now
          cells             Astronomy                                                                                          shared)
                                                 Miao        Rodriguez
   Neural networks for                                        Consuelo                                         ICMOS,         (NSF MRI
                           Neurobiology     Jack Feldman                        Adrian Cheng       Rat                                     2007 - 2008
        breathing                                             Morgado                                         Confocal         shared)
Neural networks (Voltage                                                                          Sliced
                           Neurobiology        Tom Otis                        Bernard Willers               ICMOS, 2PE     NIH Rec. Act   2009 - Now
     sensing dyes)                                                                                Brain
 Development of neural                      Carlos Portera- Peyman Golshani,                                                NIH Rec. Act
                             Neurology                                          Adrian Cheng      Mouse         2PE                        2008 - Now
       networks                                 Cailliau     Tiago Goncalves                                                  pending
High-speed Imaging Flow      Electrical                                                                                       NIH R21
                                             Bahram Jalali                                         Cells       ICMOS                       2009 - Now
       Cytometer            Engineering                                                                                       pending
  Core facility of High-                                                                                    CMOS, ICMOS,
                               CNSI         Shimon Weiss Laurent Bentolila                       Anything                CNSI internal     2008 - Now
   speed Bio-imaging                                                                                          EMCCD
  Multi-channel HAPD,                          Suyama                                                                       EMCCD, LCOS
                            Hamamatsu                                                                       2PE, EMCCD                  2006 - Now
          LCOS                                 Motohiro                                                                       donated
                                                                                                                              3 CMOS
     CMOS Cemera              Photron        Tak Takimizu                                                   CMOS, ICMOS                    2007 - Now
                                             Jeff Huber,                                                    CMOS, ICMOS,     Microscope
High-speed Microscope       Nikon, Leica                                                                                                   2009 - Now
                                            Thomas Zhapf                                                       2PE           discounted

  9/11/2012                                                  Katsushi Arisaka,UCLA                                                              44
               Concluding Remarks
   “Life” is a complex system in 4 dimensional space-time.
     Emergent property
     Strongly interacting
   Countless “spontaneous symmetry breakings” during the
    evolutional and developing process of life
   Fully controlled experiments by “Virtual Reality” under way.
     Outer world (environment) vs. Inner world (brain)

   “Ultra high-speed imaging” may reveal the fundamental
    principle of the complex life like ours.
     How can life overcome thermal fluctuation?
     Networks in a cell and between cells (neurons)

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