FAQ

Our advanced imaging system, the NL CORE, is a compact, fully enclosed, multimodal super-resolution microscope designed to make advanced optical imaging more accessible. With an integrated multi-wavelength laser source within the 47 cm by 39 cm benchtop footprint, NL Core is designed to fit directly into life-science labs without sacrificing throughput beyond the optical diffraction limit.

NL CORE has been designed to make advanced imaging easy & accessible for those working across all of life science research, enabling high-throughput, high-resolution imaging across scales spanning whole colonies and tissue sections to single cells. At a price to meet all budgets, the NL CORE can meet the needs of academic research labs; imaging core facilities; life science and bio-technology companies; and healthcare facilities!

The NL CORE features over six imaging modes, including:

Super-resolution 2D Structured Illumination Microscopy (SIM)
Confocal SIM for confocal-like background rejection
Total Internal Reflection Microscopy (TIRF)
TIRF SIM
Highly Inclined and Laminated Optical Sheet (HILO)
Brightfield
Widefield Epifluorescence

And as more imaging modes are unlocked, such as 3D SIM, the NL CORE can be upgraded as and when your needs change.

The NL CORE only has a 47 cm by 39 cm footprint, and 37.5 cm height meaning it can fit in the tightest of lab spaces or mounted on a trolley for multi-lab usage. The system only weighs 20kg, so if it needs to move from one spot to another it can be done so without special equipment or expert staff.

As a fully enclosed, light-tight certified class 1 laser system, the NL CORE can feature wherever works best for bioimaging workflows, no quiet dark room requirements needed. The NL CORE also features vibration-resistant feet, so advanced imaging can be done directly on the bio-bench.

The NL CORE can image using many conventional fluorophores across each of the integrated laser sources. Common fluorophores which are applicable include:

405nm source | DAPI, Hoechst 33342/34580, Alexa Fluor 405, Pacific Blue
488nm source | GFP, Alexa Fluor 488, FITC, CF488A, SYTOX Green
561nm source (optional) | TRITC, Alexa Fluor 555, Alexa Fluor 568, CF568, Cy3, ATTO 550, mCherry
638nm source | Alexa Fluor 647, Cy5, CF640R, ATTO 647N, SiR dyes

Using removable specimen mounts, it is easy to swap between multiple microscope slides holder, imaging dishes, or well plates, ensuring the NL CORE is compatible with all standard specimen mounting methods.

The NL CORE is capable of automated X/Y imaging through our proprietary software, providing easy to access, high throughput and high-resolution data acquisition.

The NL CORE uses an sCMOS camera as a detector instead of eyepieces to view the mounted sample, and through our easy to use, proprietary software the specimen can be brought into focus either manually by changing the samples stage z-position, or automatically by using our software-based autofocus.

The NL CORE supports long-term, live-cell imaging experiments through the optional inclusion of a stage-top incubator. Due to the lid being light-tight, the connections for the incubator are directed through the back of the imaging system, ensuring the system maintains its low footprint and light-tight imaging capabilities.

Cleverly condensed within the small 47 cm by 39 cm footprint of the NL CORE is a three-wavelength source (405nm, 488nm and 638nm), with an optional 561nm laser line upgrade. This means that each wavelength can be added into the imaging acquisition pipeline across all imaging modes through our software. If simultaneous multicolour imaging is required, this can be enabled either through third-party image splitters in conjunction with our external c-mount camera port, or through a dedicated secondary camera port upgrade.

The total z-volume which can be imaged is limited by the sample thickness and chosen objective working distance which would be 3.1mm at 10x magnification down to 0.13mm at 100x magnification, with a minimum z-step size of 312nm.

Super-Resolution SIM, sometimes called 2D SIM, is an advanced fluorescence microscopy method which overcomes the optical diffraction limit using a combination of optical and computational processes. By combining multiple images with different patterned illumination on a sample, a super-resolution image can be reconstructed with up to twice the nominal lateral resolution. As a technique, it is capable resolution doubling up to 120nm imaging resolution while maintaining fast imaging speeds at low phototoxicity.

Through our unique micromirror technology, 2D SIM imaging is not limited to small samples, ensuring structured illumination across 10x to 100x magnification scales.

Confocal SIM uses structured illumination to reject out-of-focus light, producing clearer images in scattering samples. In comparison to confocal microscopy, confocal SIM provides similar optical sectioning with lower light exposure, making it well suited for live-cell imaging.

2D SIM performs best in thin samples or close to the coverslip as the interference pattern for full resolution doubling become distorted in thick or highly scattering samples. However, driven by our innovative micromirror technology, the resolution enhancement can be scaled from 1.1x to 2x, ensuring the interference pattern is robust throughout thicker samples which enables resolution enhancement across sample thickness scales.

Total Internal Reflection Fluorescence microscopy is an oil-immersion imaging method which uses laser illumination to generate an evanescent field at the coverslip surface, exciting fluorophores within a small 100-200nm volume at the glass-water interface. This provides exceptionally high contrast when imaging at or near the cell membrane.

Highly Inclined and Laminated Optical sheet microscopy uses steeply angled illumination to create a thin light-sheet at an angle within the sample. This reduces the background fluorescence from a sample and allows for deeper imaging into cells than TIRF.

Brightfield microscopy uses light which is transmitted through a sample and is commonly used when observing stained tissue, histology sections, microorganisms and morphology as well as observing cell confluency and viability. It is a simple and fast imaging mode ideal for routine specimen screening.

Widefield microscopy illuminates the entire field of view simultaneously and is therefore well-suited for rapid imaging of fluorescently labelled cells, tissue, and dynamic biological processes across fields of view. It can be used as a check on how well a sample has been labelled.

The NL CORE can acquire z-stacks and timelapse images across 10x-100x magnifications and across all integrated wavelengths within the system. Each imaging mode is also capable of being combined with z-stack and time series imaging.

The system is compatible with any objective in the Evident X-Line, meaning imaging can be performed across scales from 10x magnification to 100x magnification. In the future, we will also be including Nikon range objectives as an option.

Any CMOS camera with both a 6.5μm pixel size or smaller and has a c-mount can be attached externally to the system for bioimaging. The NL CORE is currently primarily compatible with Hamamatsu cameras, and in the future we are interested in expanding the range of camera manufacturers, though please get in touch if a specific camera is desired with the system.

The NL CORE features up to 4 laser lines within its compact 47 cm by 39 cm footprint, with 405nm, 488nm and 638nm included as standard and a 561nm line available on request. Each laser can be imaged with sequentially using our proprietary NL CONNECT software.

Using the Hamamatsu Orca Flash 4.0, a maximum framerate of 30 fps at the full 2048 x 2048-pixel resolution over USB is achievable, though this speed can be improved at smaller fields of view.

We have included within the NL CORE a multi-band dichroic and emission filter, ensuring much of the laser excitation is rejected from the detection path and ensuring each respective emission wavelength can be captured without the need to switch through emission filters. Optional additional filters can be added by the user in the future.

No - our proprietary, easy to use software the NL CONNECT is included alongside the NL CORE.

Regardless of imaging mode, data is saved in an open-source OME-TIFF format to ensure you can maintain using your already established image analysis and processing pipelines.

The NL CORE has been designed to connect and run on rudimentary research laptops with accessible specifications e.g. 8GB RAM, Intel Core Ultra 5 processor.

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