1. Smart imaging devices for BioImaging
Lars Hufnagel
EMBL Heidelberg
In collaboration with
Hamamatsu Photonics
and Luxendo GmbH

2. Deciphering molecular basis of life requires cross scale imaging
> Imaging technologies that can cross spatial and temporal scales
<1um
<100um
> 1mm
Systematic map of molecular
mechanisms at the cellular level
Mechanistic understanding
at tissues, organisms and disease
New CRISPR genomic engineering tools allow to specifically label and
manipulate almost every gene/protein in living cells.

3. Fast 3D imaging In toto embryo imaging time Photo-toxicity 800 seconds
Confocal microscope
Light-sheet microscope
area detector
200μm
point detector
In toto embryo
imaging time
800 seconds
<1 seconds
light sheet thickness
~number of planes
Photo-toxicity
Pioneered at EMBL Heidelberg
Huisken, et al, 2004

4. Imaging biological specimen across scales
3D live imaging
Fruit fly
Zebrafish brain
Mouse embryo
Krzic et al, Nat Methods 2012
Strnad et al, Nat Methods 2015
Light sheet nanoscopy
Quantitative measurements
Capoulade et al, Nature Biotechnology 2011
P. Hoyer, J. Engelhardt, S. Hell, L. Hufnagel PNAS 2016

5. Where will we go? feasible today future 2Mpixels 4Mpixels 8-16Mpixels
5TB/day
23TB/day
>160TB/day

6. Realtime data processing
Phallusia imaging
Digital representation
GPU and FPGA based processing
GPU–based realtime compression library for fluorescent images with up to 1GB/s yields 1/30 compression
Realtime data processing
and segmentation

7. On sensor scattering discrimination
readout
activation
front
constant
reset
dumped
Gustavo de Medeiros, et al Nat Comm 2015
Patent Pending

8. Summary
Light sheet microscopy allows 3D imaging of biological specimen at low light levels for extended periods of time.
Light sheet microscopy is compatible with a vast variety of molecular imaging techniques.
Integration of realtime data processing will be vital for future applications
Light sheet imaging would profit from:
Gated or time-resolved imaging (~ns)
molecular environment
protein-protein interaction
kinetics, concentrations
Large (>16MP) small pixel size (1-2um) sensor with low noise (<1e rms) with high sensitivity (QE>80%) in VIS to NIR range.
Integration of data processing and imaging
Hyperspectral imaging in the VIS range