all-rounder demonstrated with advanced application examples China International Optoelectronic Conference 2013 （CIOEC） China International Advanced Optical Manufacturing & Precision Engineering Forum 2013 Optical Testing Technology Session Light – a testing all-rounder demonstrated with advanced application examples Hexin Wang, China Innovation and R&D Center, Carl Zeiss Shanghai Shenzhen, 9/5/2013

Agenda 1 Introduction 2 Examples Interferometer - Extremely persistent engineering Light Sheet – Success of knowledge transfer OCT – Diversity of applications 3 Discussions

Light – a testing all-rounder demonstrated with advanced application examples When you see the Moon way up in the sky, it’s hard to get a sense of perspective about how big the Moon really is. Just how big is the Moon compared to Earth? Let’s take a look at the diameter first. The diameter of the Moon is 3,474 km. Now, let’s compare this to the Earth. The diameter of the Earth is 12,742 km. This means that the Moon is approximately 27% the size of the Earth. Read more: http://www.universetoday.com/20489/moon-compared-to-earth/#ixzz2auwP9xCF May 2013

Light – a testing all-rounder demonstrated with advanced application examples  20 July 1969 When you see the Moon way up in the sky, it’s hard to get a sense of perspective about how big the Moon really is. Just how big is the Moon compared to Earth? The average center-to-center distance from the Earth to the Moon is 384,403 kilometres (238,857 miles) The average center-to-center distance from the Earth to the Moon is 384,403 kilometres (238,857 miles), which is about 30 times the diameter of the Earth. The Moon has a diameter of 3,474 kilometres (2,159 miles)[1] — slightly more than a quarter that of the Earth. This means that the volume of the Moon is only 1/50th that of Earth. Its gravitational pull is about a 1/6th of Earth's. The Moon makes a complete orbit around the Earth every 27.3 days, and the periodic variations in the geometry of the Earth–Moon–Sun system are responsible for the lunar phases that repeat every 29.5 days. The gravitational attraction, and the centrifugal forces generated by the rotation of the Moon and Earth around a common axis, the barycentre, is largely responsible for the tides on Earth. The energy dissipated in generating tides is directly responsible for the reduction in potential energy in the Moon-Earth orbit around the barycentre, resulting in a 3.8 cm yearly increase in the distance between the two bodies.[2] The Moon will continue to move slowly away from the Earth until the tidal effects between the two are no longer of significance, whereupon the Moon's orbit will stabilize. Read more: http://www.universetoday.com/20489/moon-compared-to-earth/#ixzz2auwP9xCF The most advanced interferometer in the production could be used to measure the profile depth of about 0,5 nm (rms) of a shoe sole! In other words, if we enlarge a shoe to a length which is equal to the distance between the earth and moon (about 384,403 km), a profile depth of about 0,50 m of such a shoe sole could be measured! May 2013

Agenda 1 Introduction 2 Examples Interferometer - Extremely persistent engineering Light Sheet – Success of knowledge transfer OCT – Diversity of applications 3 Discussions

Interferometry is the central tool of optical metrology

Basic principle of interferometry One Newton fringe is equivalent to a distance change of λ/2

Basic principle of interferometry Nature of Newton fringes for different surfaces with reference to a standard flat

Basic task of digital fringe analysis Fringe analysis: Development of algorithms to calculate surface deviations from interferograms

Basic principle of Fizeau Interferometers Fizeau Interferometers are the workhorse in optical metrology

Fizeau interferometers Beamsplitter Test piece Beam expander Fizeau lens Laser Cavity CCD camera

Carl Zeiss interferometer DIRECT 100 Transmission sphere APLANAR Fizeau plate Cavity More flexibility Enabling of multi-fringe technique

Carl Zeiss interferometer DIRECT 100 Polarizing beamsplitter l/4 plate Better light efficiency Suppression of residual reflections

Carl Zeiss interferometer DIRECT 100 Rotating wedge Reduction of coherent noise

Carl Zeiss interferometer DIRECT 100 DMI : Direct Measuring Interferometry Video pipeline processing Reference store 3x3 convolution Sine Frame store Look-up table Arctan Minus Accumulation store 3x3 convolution Cosine

Carl Zeiss interferometer DIRECT 100 Vertical test tower arrangements Transmission spheres APLANAR

Carl Zeiss interferometer DIRECT 100 Control software

Carl Zeiss interferometer DIRECT 100 Repeatability RMS of wavefront repeatability as function of cavity length for 2 different temperature fluctuations and 2 different air pressures

Carl Zeiss interferometer DIRECT 100 Repeatability in production environment Repeatibility 0.2 ... 0.6 nm RMS

Carl Zeiss interferometer DIRECT 100 Reproducibility in production environment 0.5 ... 1.0 nm RMS

Carl Zeiss interferometer DIRECT 100 Calibration process Measured wavefront of total setup - Wavefront error of calibration surface - FE wavefront of calibration surface Actual calibration wavefront

Carl Zeiss interferometer DIRECT 100 Accuracy in production environment 0.7 ... 1.5 nm RMS

Carl Zeiss interferometer DIRECT 100 Conclusions Visual interferometry : Resolution /10 Digital interferometry : Resolution /1000 ... /10000 Repeatability : Main limitations by temperature fluctuations coherent noise Reproducibility : Main limitations by handling Accuracy : Main limitations by calibration process

Agenda 1 Introduction 2 Examples Interferometer - Extremely persistent engineering – Leading/enabling technology in the production environment Light Sheet – Success of knowledge transfer OCT – Diversity of applications 3 Discussions

Light sheet Application demonstrated in the movie http://www.youtube.com/watch?v=mr834Cs9ncs

Light sheet Mature technology used in the metrology

Light sheet Light Sheet Microscopy for Multiview Imaging of Large Specimens Optical sectioning while minimizing photodamage Very sensitive fluorescence detection Image acquisition rate as fast as possible Imaging large volumes with high resolution and contrast http://www.cell.com/cell_picture_show-lightsheet

Light sheet Light Sheet Microscopy for Multiview Imaging of Large Specimens Applications Embryogenesis of Drosophila, Zebrafish and other model organisms Cellular dynamics in embryos and small organisms Structural imaging of larger (µm-mm) organisms C. Staber , J. Zeitlinger, Stowers Institute for Medical Research, Kansas City, USA

Light sheet Z.1 by Carl Zeiss - Innovation More Images. Gentle. Fast.

Light sheet Z.1 by Carl Zeiss - Innovation Shrimp MicroScoptail by Anastasios Pavlopoulos, Benjamin Harich, Stephan Saalfeld, and Pavel Tomancak Max Planck Institute of Molecular Cell Biology and Genetics This time-lapse recording shows a transgenic embryo from the crustacean amphipod Parhyale hawaiensis labeled with a histone-RFP fluorescent marker. The embryo was recorded for more than 4.5 days at 7.5 min intervals on a Zeiss Lightsheet Z.1 microscope using a 20x/1.0 detection objective. The movie plays 12 time points per second, displaying Parhyale development 5,400 times faster. The embryo was imaged with two lightsheets from its ventral and two ventro-lateral sides; these views cover about two-thirds of the specimen, leaving a wedge open on the dorsal side. The images from the left and right lightsheets were fused on the fly by the Zeiss ZEN software during acquisition. In each time point, the resulting three views were registered using beads scattered in the agarose around the specimen and fused into a single nearly isotropic volume with content-based fusion algorithm, and 3D rendered rotating by one degree per time point around the x axis. All processing was done in Fiji (http://fiji.sc), the rendering using ImgLib2 (http://fiji.sc/ImgLib2). The movie starts at 3 days after egg lay, when a distinct germ band has formed ventrally and is surrounded by large spaced-out nuclei of extra-embryonic cells. Segment formation and maturation progresses from anterior to posterior and is accompanied by embryo elongation posteriorly and ventrally. During these stages, the embryo develops a series of specialized appendages along the anterior-posterior axis that can be observed projecting ventrally, elongating and segmenting along their proximodistal axis. http://www.cell.com/cell_picture_show-lightsheet2#iit=

Light sheet (LS) Examples of imaging done with LS Microscopy based systems Gutiérrez-Heredia Luis et al, Light Sheet Fluorescence Microscopy: beyond the flatlands Current Microscopy Contributions to Advances in Science and Technology (A. Méndez-Vilas, Ed.), 2012

Agenda 1 Introduction 2 Examples Interferometer - Extremely persistent engineering – Leading/enabling technology in the production environment Light Sheet – Success of knowledge transfer - Innovation OCT – Diversity of applications 3 Discussions

“Optical equivalent Ultrasound” What is OCT? “Optical equivalent Ultrasound” OCT imaging is performed by measuring the echo time delay of light back reflected/scattered in tissue Near infrared light (800-1300nm) micrometer resolution millimeter penetration depth Non-contact and high speed

OCT How does it work? OCT is a non-invasive, sub-surface imaging technique capable of providing high resolution cross sectional images of biological tissues such as retina. OCT empowers you with the details of “What lies beneath the fundus image?” Optic Nerve Head Ref Mirror Ophthalmic Lens Retina XY Scanner SLD superluminescent light emitting diode (SLD).超冷发光二极管光源 Detector Display & Report generation Processing & Analysis Macular B-scan (Temporal  Nasal)

Time Domain OCT & Spectral Domain OCT Reference Mirror Eye Light Source Reference Mirror Spectrometer Cirrus (3rd generation) Spectral-Domain OCT Light Source Eye Stratus OCT™ Single Detector Stratus(1st generation) Time-Domain OCT This very simple diagram demonstrates the basic difference between time domain OCT and Spectral Domain OCT. TD-OCT uses a single detector. The reference arm must move to capture the depth of the scan . SD-OCT uses a spectrometer for image acquisition. The reference arm does not move. This allows the full A scan to be captured simultaneously. Therefore spectral domain provides faster scanning. Because of the faster scanning, more data can be captured, therefore you can obtain a higher resolution image (as seen here) or a cube of data • SD-OCT is about 50 times faster than time domain • It is possible to acquire and view a cube of data with SD-OCT • The commercial SD-OCT instruments listed above have 5–6μm resolution (compared to 10μm of TD-OCT) Faster speed Higher definition

OCT Diverse applications in clinical practice Ophthalmology Standard clinical tool in eye imaging guided surgery and diagnose from anterior corneal segment to posterior eye disease, such as AMD\Glaucoma\Diabetic Retinopathy Cardiology Ongoing development as an intravascular imaging tool for coronary plaques and stent, visualization for lesion assessment, treatment and follow-up strategies Oncology Great potential as an optical biopsy tool for detection of many cancer tissues such as skin, esophagus etc. …

Agenda 1 Introduction 2 Examples Interferometer - Extremely persistent engineering – Leading/enabling technology in the production environment Light Sheet – Success of knowledge transfer -Innovation OCT – Diversity of applications - More innovation 3 Discussions

Discussions Interferometer - Extremely persistent engineering => Leading/enabling technology in the production environment Light Sheet – Success of knowledge transfer => Innovation OCT – Diversity of applications => More innovation, even disruptive! Thanks to my colleagues: Mr. Bernd Dörband, Mr. Bu Peng, Mr. Jörg Mütze for sharing slides!

Carl Zeiss Group: Our portfolio is focused on high-tech The overarching ZEISS brand stands … … for customer focus, innovation and reliability Strategic Business Units Semiconductor Manufacturing Technology Industrial Metrology Microscopy €967 million in revenue 2,636 employees €495 million in revenue 2,239 employees €650 million in revenue 2,801 employees Medical Technology Vision Care Camera Lenses, Sports Optics, Planetariums €984 million in revenue 3,450 employees €860 million in revenue 9,586 employees €178 million in revenue 767 employees Financial Highlights for FY 2011/12 May 2013