A Multimodal Lensless Microscope

Illustration of a novel digital in-line holographic microscopy (DIHM) in-vitro imaging technology. (Source: ChipScope.eu)

Today’s state-of-the-art analysis of biological samples by light micro­scopy includes a vast variety of techniques ranging from conven­tional bright field micro­scopy and phase contrast micro­scopy to high resolution confocal laser scanning micro­scopy and to recently developed super resolution microscopy techniques like stimulated emission depletion (STED) or stochastic optical recon­struction micro­scopy (STORM) which abnegate Abbe’s limit of diffraction. Despite the availability of these sophis­ticated, super resolution techniques, reproducible visuali­zation of cells and identification of subcellular structures in bio­logical samples still requires staining with dyes or immuno­labeling by antibodies to specific cellular antigens.

Generally, in-vitro obser­vation of living cells can provide valuable insights into their structure and dynamics including orga­nization of organelles and trans­duction of chemical signals involved in cell–cell and cell–matrix inter­actions. Unfor­tunately, there is a limited use for long term in-vitro imaging as most high-resolution micro­scopy tech­nologies require processed/fixed tissues or cells. As both high resolution optical micro­scopy and fluores­cence imaging usually require highly skilled users, expensive equipment and main­tenance, the presented novel digital in-line holo­graphic micros­copy (DIHM) in-vitro imaging tech­nology opens a vast field of applications for standard users. This ana­lytical optical system offers quick and reproducible results at low costs. Moreover, it voids the necessity of referral to specia­lized labs and is easily implemented as a diagnostic tool for doctors.

DIHM is based on the numerical recon­struction of a digitally recorded hologram. It allows for the acqui­sition of both, the amplitude and phase information of a wave front shaped by the microscopic sample. The advantage of the DIHM lies in the simplicity of its setup: the micro­scope consists of a light-emitting diode as an illumination source, appro­priate filtering for coherence enhance­ment and an image sensor. The compre­hensive data processing algorithm transforms the recorded holograms into a micro­scope image by angular spectrum approach and digital filtering. In general, the resolution of such a microscope is strongly influenced by the spatial coherence length of the illumination, which can be enhanced via reducing the emitting area, either by cutting a part of the wave front with the pinhole or by use of a point-like nanoLED. The nanoLED arrays developed within the EU Horizon 2020 program ChipScope project will allow enhance­ment of the imaging resolution compatible to the conventional optical micro­scopy.

This fact makes lensless microscopy an ideal tool for medical diagnosis in remote areas since there is no need for the medical doctor to bring and maintain large, heavy and sensitive analysis devices. A simple laptop and a suitcase sized lensless micro­scope assembly is enough to make a parasite diagnosis from body fluid samples. The robust con­struction enables a fast, reliable and automated analysis of the specimen by combining not only high-resolution light micro­scopy but also imple­menting modern analysis techniques based on the detection of changes in human DNA, iden­tifying viral genomes and immuno­logical charac­terization in one device. To provide the highest light sensi­tivity and optical resolution, the system is equipped with a normal grayscale camera to work in a multi-cell imaging bright field mode. This novel lensless micro­scope is equipped with a microfluidic flow channel system for handling living cells and imaging. (Source: Cordis)

Reference: G. Scholz et al.: Continuous Live-Cell Culture Imaging and Single-Cell Tracking by Computational Lensfree LED Microscopy, Sensors 19 , 1234 (2019); DOI: 10.3390/s19051234

Link: Laboratory for Emerging Nanometrology LENA, Technische Universität Braunschweig, Braunschweig, Germany

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