Drug Discovery

Inverted Microscope Systems

ECLIPSE Ti2-E / Ti2-LAPP: Synchronous operation of the Ti2-E inverted microscope with Ti2-LAPP illuminator modules and other hardware devices allows for complex multidimensional image acquisitions. Additionally, the Ti2-E features the Perfect Focus System 4 (PFS4) focus-locking system, providing the highest level of stability for extended imaging.

ECLIPSE Ji: The Ji is a digital microscope developed to support drug discovery research. Pre-defined assays are available to automatically perform numerous routine experiments, such as counting cells, measuring fluorescence expression efficiency, and measuring apoptosis. The instrument takes care of troublesome focus and exposure adjustments and supports the analysis of experimental results by displaying results per cell and per plate in an intuitive graphical interface.

Selecting a Microscope System for your Drug Discovery Model

Model systems for drug discovery run just about the entire range of possibility, from in vitro adherent cell cultures to whole model organisms and almost everything in between. Complex 3D cell culture models such as spheroids, organoids, and organs-on-chips can be composed of multiple cell types to better recapitulate various physiological characteristics lost in traditional adherent cell cultures, which are the traditional standard for high throughput screening. Additionally, organoids can even be cultured from autologous (patient-derived) cells for developing precision medicines.

Widefield fluorescence imaging is an appropriate choice for relatively flat samples, such as adherent cells cultured in multi-well plates, the traditional standard for high throughput screening. It is fast, sensitive, and cost effective, but does not provide intrinsic optical sectioning – the ability to effectively image a single plane in a thick 3D specimen.

Physically larger 3D models, such as organoids and tissue, may require an imaging technique with optical sectioning capabilities to capture the features of interest without being overly compromised by out-of-focus blur. Confocal microscopy is the standard for such applications, Nikon offers the AX / AX R confocal microscopes, point-scanning systems which can be configured on the BioPipeline LIVE and BioPipeline PLATE systems for imaging discrete sections up to several hundred micrometers deep in various samples.

While confocal imaging is a suitable choice for optical sectioning at depth, sometimes it is insufficient. In vivo imaging in the presence of thick and scattering tissues often necessitates the use of multiphoton imaging, such as the Nikon AX R MP multiphoton microscope system, which uses multiphoton excitation with near-infrared to infrared light to minimize out-of-focus excitation and scattering.

Enhancing Drug Discovery Research using Artificial Intelligence

One of the great advantages of image-based assays is their rich information content. Until recently, however, relatively little of this information could be leveraged in a practical manner. However, new approaches based on artificial intelligence (AI), and particularly deep learning (DL) methods using artificial neural networks (ANNs), allow for deeper correlations between image features to be inferred and applied towards characterizing morphology and phenotype. Such analytical approaches have been referred to as “cell profiling” or “image-based profiling,” and represent a very active area of development.

In addition to profiling, DL can be used to help accelerate and strengthen image analyses in other ways. Nikon is committed to the design of reliable DL-based image analysis tools under the umbrella of NIS.ai – a series of software modules available for the NIS-Elements software. For example, the Segment.ai module can be trained to automatically segment difficult image features that are difficult to isolate using classical approaches.

Other NIS.ai modules of potential application for drug discovery work includes Convert.ai, which can be trained to predict image features from a fluorescence channel using only a brightfield or another transmitted light channel as a reference, which can help cut down on both cytotoxicity (from the fluorescent label) and phototoxicity (from the high intensity light used for fluorescence imaging). Relatedly, the Enhance.ai module can be trained to predict a higher signal-to-noise version of noisy image data. This allows for a reduction in illumination intensity, and thus phototoxicity.

High throughput widefield fluorescence imaging of larger model systems, such as organoids, can benefit from our Clarify.ai module, which is pre-trained to provide automatic blur removal from widefield fluorescence microscopy images. This allows for users to benefit from the speed of widefield fluorescence imaging, but with enhanced optical sectioning and without the need for a confocal system.

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Neurites in phase-contrast were not possible to define accurately by traditional thresholding. Segment.ai was trained on hand-traced neurites (human recognized) and learned how to trace neurites in subsequent images.

Nikon Contract Imaging Services for Pre-Clinical Drug Discovery Research

The Nikon BioImaging Labs provide contract research services to their local biotech and research communities, as well as remote services* for clients located elsewhere. With locations in Cambridge, MA, USA, Leiden, The Netherlands, and Shonan, Japan, the Nikon BioImaging Labs have significant experience working with customers in the biopharma research space and performing confocal microscopy of organoids and other 3D cell culture systems now used for drug discovery studies, including various commercially produced organ-on-chip models.

The Nikon BioImaging Labs are not only capable of data acquisition, but their full-service capabilities also extend to assay design, assay development, assay validation, cell culture, sample preparation, and data analysis. If you would like to learn more and see if services at one of the Nikon BioImaging Labs is right for you, please don’t hesitate to contact us to set up a free consultation.

* The service may vary depending on the facility. Please contact the Nikon BioImaging Lab near your location for details.

Nikon contract research services at a glance.