CUTTING EDGE TECHNOLOGY

All-in-One design

Combining elements of science and design, DeNovo was developed as an automated enclosed system that requires no manual intervention.

Boasting a small footprint and touchless automation, DeNovo leverages various engineering disciplines in an effort to maximize functionality, technical efficacy and reliability. DeNovo is seamlessly integrated into laboratory environments as an enclosed system, minimizing the possible effects of light, temperature and vibrations during system operation, and allowing for more reliable imaging, analysis, quantification and phenotyping of CTC.

Sample handling

Supporting the various enrichment techniques, DeNovo’s sample carrier is designed to transfer samples from the loader to the scanning chamber safely and efficiently.

Different enrichment techniques rely on dedicated devices with complex geometrical structures that capture the fluorescent-stained, enriched cells. DeNovo's sample carrier supports all enrichment devices, ranging from standard glass slides, through micro-sieve and membrane, to 3D microfluidic chips. Multiple samples are transferred between the loader and scanning chamber, using an innovative magnet clip that eliminates any physical contact with the sample. DeNovo’s unique sample-handling technique minimizes loss or damage to the samples and saves valuable time.

LED Fluorescent Light Source

With 20,000 operational hours and no warmup or cool down time, the LED fluorescent light engine is a superior illumination source, reducing intensity fluctuations and providing unmatched stability.

High Throughput Imaging

Combining sophisticated image processing with auto-focus and 3D imaging, custom-designed optics and advanced digital imaging, DeNovo is able to scan samples at exceptionally high rates.

Sophisticated assay-specific, logic-based automated imaging processes allow DeNovo to avoid capturing fields that don't contain CTC, substantially reducing the single-sample scan time. Together with its rapid and robust focusing algorithms and 3D imaging algorithm that allows for rapid and effective z-axis movement, DeNovo's capture time is reduced to a minimum and system throughput is dramatically increased.

CTC Coordinate Synchronization

Utilizing its high-precision motorized stage, DeNovo records an accurate coordinate for every cell in the sample, allowing it to be synchronized with any cell-picking instrument, and supporting rapid and accurate redetection for further molecular testing.

Solo Workstation – Local Review & Analysis Workstation

A central element of the DeNovo solution, Solo Workstation was designed to ease and streamline the CTC detection workflow, enabling review and analysis of test results on a remote workstation during the scanning process. The stand-alone workstation includes advanced review and analysis tools, as well as report-generation and archiving features.

SoloWeb – Web-Based Review & Analysis

Through standard web browsers in any location, SoloWeb provides complete and secure web review, analysis, reporting and consulting of all DeNovo-scanned cases.

SoloWeb employs embedded communication and management features, enabling real-time remote review, analysis and reporting of cases, as well as second opinion, consultations and professional guidance.By facilitating and simplifying the test review and analysis processes, and making them accessible from any remote location, SoloWeb improves efficiency and productivity, as well as cooperation between experts. Ultimately, better communication throughout the workflow increases the quality of the reported results.

Out-of-the-box automated CTC imaging & detection

DeNovo's integrated CTC imaging and analysis programs can be put to use immediately, detecting and characterizing CTC regardless of the samples' processing method and applied markers, requiring only minimal optimization.

Deep Learning Analysis Algorithms

At the heart of automated CTC detection, DeNovo's innovative deep learning algorithms enable accurate image analysis that considers the many different biometric characterizations of CTC.

CTC research and clinical practice utilize numerous enrichment techniques, markers and processing protocols, which, when combined, greatly influence the different biometric characteristics of CTC. Together with the fact that CTC definitions are often a combination of dozens of different variables, the transition to automated, machine vision-based CTC characterization requires intricate translation of visually-confirmed CTC characteristics, to a robust and accurate automated detection algorithm. DeNovo's innovative automated, deep learning algorithms allow the expert to perform initial visual confirmation of CTC images captured by DeNovo, and reuse the confirmed CTC images to automatically enhance the detection algorithms. The enhanced algorithms are seamlessly applied to all future automated imaging process, while insights derived from numerous samples are combined to provide a wider statistical analysis, improving the overall accuracy of the automated detection process.

CTC research and clinical practice utilize numerous enrichment techniques, markers and processing protocols, which, when combined, greatly influence the different biometric characteristics of CTC. Together with the fact that CTC definitions are often a combination of dozens of different variables, Read More

Dynamic CTC Libraries

Assay specific CTC libraries can be created and continuously be updated as additional samples are scanned and additional CTC are detected. CTC libraries can be used for training, reference aid for analysis as well as be shared between remote users / customers / collaborators utilizing BioView web review, analysis and report application, the Soloweb, to further exploration and study

Automated FISH Imaging & Analysis

Leveraging BioView’s field-proven, FDA-cleared FISH applications, DeNovo preforms automated, high-resolution imaging and analysis of CTC, hybridized with any FISH probe.

Utilizing BioView’s field-proven, FDA-cleared FISH imaging and analysis technology, DeNovo can be utilized to automate high-resolution imaging and analysis of CTC, hybridized with any commercially-available or home-brewed FISH probe. These include, but are not limited to: Her2/Neu, ALK, ROS1, MET, RET, PTEN, CEP8 and more.DeNovo's automated FISH application can be tailored to any specific FISH probe (up to six different colors in a single run), while also supporting both high-resolution dry objectives and oil-immersion objectives, when a higher resolution is required.

Target FISH

Leveraging BioView's Target FISH (T-FISH) application, DeNovo provides a cross-referenced genetic content analysis of CTC.

Supporting the utilization of FISH technology as a diagnostic method for liquid biopsies, DeNovo’s Target FISH (T-FISH) application enables the genetic analysis of a specific, pre-selected subset of target cells. It first scans slides stained with Immuno Fluorescent antibodies (IFL) to detect CTC, then redetects them after the samples have been hybridized with FISH probes (IF and FISH can also be co-hybridized). The two scans are automatically matched to present two images of the same cell for each and every CTC in the sample (IF/FISH or IFL/FISH or FISH/FISH).

CTC Characterization

Presentation of signal and nucleus measurements for every cell captured

CTC assay development often involves careful characterization of various signal and morphometric cell attributes. The digital presentation of meaningful information, relevant to accurate characterization of cells of interest is facilitated by dedicated “Research” mode. BioView’s Research mode presents gallery of cells of interest alongside an excel spreadsheet displaying various cell attributes. Measured data can be seamlessly exported to local database, for further analysis and documentation.

Automated 3D imaging

Utilizing a field-tested, sophisticated dynamic z-stack imaging algorithm, DeNovo ensures that each fluorescent marker is captured in its accurate focal plane.

Automated imaging techniques that can capture cells and markers at various focal planes are a key element for accurate detection, measurement and presentation of targeted cells. Protein structures, for example, often reside in different focal planes than that of the nucleus. Cells too, isolated using filtration membranes and various microfluidic chip designs, may be located in different focal planes as far as 150 microns from each other. Automatically calculating the number of layers required for each fluorophore, regardless of their respective z-plane, DeNovo’s dynamic z-stack imaging algorithm successfully captures each cell's fluorescent markers in its accurate focal plane. Additionally, its deep z-stack algorithm allows for rapid and effective z-axis movement, while DeNovo performs automated capturing of cells and markers, reducing capture time to a minimum and increasing system throughput. An accurate composite image is automatically constructed from all captured z planes, providing a clear and informative image of the cell. 

Automated imaging techniques that can capture cells and markers at various focal planes are a key element for accurate detection, measurement and presentation of targeted cells. Protein structures, for example, often reside in different focal planes than that of the nucleus. Cells too, isolated Read More

Automated Focus

Incorporating innovative focusing algorithms that ensure no field loss, DeNovo supports rapid detection and capturing of even the smallest number of cells present in various focal layers and across large surfaces.

Rapid detection of the focal levels in which cells can be seen has critical implications on scan time and accurate detection. In the past, methods such as focus mapping and focus extrapolation based on focal planes using a set of focus anchors, were widely used. However, automated focusing on enriched CTC samples poses a number of challenges, which include: Low cellular density: When no cellular content can be found in the majority of the scanned area, the focal planes method cannot be used, as focusing on every field, results in an extremely long scan time. Cell distribution across multiple, distant focal layers within and between fields: When membrane filtration techniques are used, and even more so when cells are trapped in microfluidic chips, it is impossible to predict the focal plane in which cells are present. With no continuity between the focal planes of adjacent fields, automated focusing becomes extremely challenging. If these challenges are to be dealt with successfully, a more advanced focus technique, one that has been adopted specifically to CTC samples, is required. To address the need for rapid and robust focusing, DeNovo incorporates an innovative set of focusing algorithms, dedicated to ensuring no field loss, while ensuring the proper detection and capturing of the smallest number of cells present in various focal layers across large surfaces. Rapid detection of the focal levels in which cells can be seen has critical implications on scan time and accurate detection. In the past, methods such as focus mapping and focus extrapolation based on focal planes using a set of focus anchors, were widely used. However, automated focusing on enriched CTC samples poses a number of challenges, which include:Low cellular density: When no cellular content can be found in the majority of the scanned area, the focal planes method cannot be used, as focusing on every field, results in an extremely long scan time.Rapid detection of the focal levels in which cells can be seen has critical implications on scan time and accurate detection. In the past, methods such as focus mapping and focus extrapolation based on focal planes using a set of focus anchors, were widely used. However, automated focusing on enriched CTC samples poses a number of challenges, which include:Low cellular density: When no cellular content can be found in the majority of the scanned area, the focal planes method cannot be used, as focusing on every field, results in an extremely long scan time.Cell distribution across multiple, distant focal layers within and between fields: When membrane filtration techniques are used, and even more so when cells are trapped in microfluidic chips, it is impossible to predict the focal plane in which cells are present. With no continuity between the focal planes of adjacent fields, automated focusing becomes extremely challenging.If these challenges are to be dealt with successfully, a more advanced focus technique, one that has been adopted specifically to CTC samples, is required.To address the need for rapid and robust focusing, DeNovo incorporates an innovative set of focusing algorithms, dedicated to ensuring no field loss, while ensuring the proper detection and capturing of the smallest number of cells present in various focal layers across large surfaces.

Rapid detection of the focal levels in which cells can be seen has critical implications on scan time and accurate detection. In the past, methods such as focus mapping and focus extrapolation based on focal planes using a set of focus anchors, were widely used. However, automated focusing Read More

Precise Imaging

Automated exposure algorithms and high quality, assay-specific optics ensure highest imaging fidelity and accurate imaging results, which are standardized and reproducible throughout the samples.

In an effort to ensure the highest imaging fidelity, DeNovo utilizes unique automated exposure algorithms which verify that all captured images are properly exposed and re-measured, with no operator intervention. With its unique live-image processing, DeNovo ensures image quality is standardized and reproducible throughout the samples, and provides an accurate presentation of the information. Additionally, by maximizing the light that reaches the sample, DeNovo's custom-designed optics improve the efficiency of fluorescent imaging compared to standard fluorescent microscopy. Various objectives with different optical properties are carefully selected to match the required resolution, sample geometry and quantitative objects of each specific assay. These range from high-distance to oil-immersion objectives, through hard-coated, fluorophore-specific fluorescent filters, to highly-sensitive CMOS camera with enlarged pixel array and high quantum efficiency across the spectrum. Precise matching of theses optical components with the assay-specific characteristics guarantees reliable and accurate imaging results. 

In an effort to ensure the highest imaging fidelity, DeNovo utilizes unique automated exposure algorithms which verify that all captured images are properly exposed and re-measured, with no operator intervention. With its unique live-image processing, DeNovo ensures image quality Read More