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Sampling Device for High-Throughput Light-Sheet-Based Microscopy


Abstract

Light-sheet-based fluorescence microscopy (LSFM) is a powerful method to analyze 3D living or fixed biological samples - such as cell cultures, embryos, or tissue - with high temporal resolution. The novel sampling device facilitates high-throughput LSFM measurements without loss of imaging quality.


Background

Light-sheet-based fluorescence microscopy (LSFM) is an extremely efficient light-optical tool to monitor 3D fluorophore distributions in biological samples. In comparison to state-of-the-art, e.g. confocal, fluorescence microscopy, the light-induced stress is reduced by orders of magnitude. Hence, LSFM is especially suited for imaging of sensitive specimen, living tissue, or living plants over long periods of time. In addition, the method provides a high imaging speed and an exceptional resolution of fixed and cleared probes. However, similarly to inverted microscopy, most LSFM setups require a non-planar positioning of the sample. Hence most commercially available LSFM setups are limited in their application for cell-based high-throughput screenings.


Images & Videos


Solution

The novel sampling device, which may be combined with standard multi-well plates, was developed to facilitate high-throughput screenings of biological probes such as multicellular spheroid cultures. This is achieved by position-ing of the lighting source and the detection device below and at 45° angles to the sample. By introducing a customized zigzag shape of the microtiter plate (see figure) the lens distance is minimized facilitating selection of matching lenses. In addition, a novel holder has been developed mounting both lenses, which can be rotated around its axis and tilted. Hence, lenses with smaller working distances and larger diameters can be employed. Due to the rotation, different perspectives can be obtained. By employing identical lenses for excitation and detection these functions are interchangeable by rotation of the mirrors further accelerating the imaging process. The novel setup allows for an accelerated - thus both time- and cost-efficient - throughput compared to standard LSFM measurements.


Advantages

  • Increased throughput for 3D imaging
  • Suitable for component screenings, e.g. multicellular spheroids
  • Excitation and detection below the sample
  • Novel cuvette design minimizes spheric aberration

Scope of application

  • Toxicity tests
  • Drug screenings
  • Clinical and preclinical trials
  • Personalized medicine

Service

Licensing or assignment of the technology is possible as well as a cooperation for further development of the invention.


INNOVECTIS Gesellschaft für Innovations-Dienstleistungen mbH

Kirstin Schilling
06925616320
info@innovectis.de
www.innovectis.de
Address
Altenhöferallee 3
60438 Frankfurt



Patent situation

  • DE 102013110093B3 granted
  • WO 2015036589 pending
  • EP 14 765 957.7 pending

Keywords

Light-sheet-based fluorescence microscopy (LSFM)

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