The Innovators 2020
Showcasing the products and companies making a difference in 2020
Getting More Data Out Of The Day With The Zulu RT®
Accelerating real-time PCR results with accuracy and sensitivity
The Zulu RT® is a rapid, modular qPCR instrument capable of performing up to four six-channel, 40-cycle qPCR reactions in less than 20 minutes. The modular design is a defining feature of the tool – it enables four independent qPCR analyzers in one chassis to perform these independent reactions simultaneously. The fast processing time of the Zulu RT is achieved through its unique thermal design, with rapid ramp rates for heating (15°C per second) and cooling (12°C per second), thin-walled PCR tubes, and precise temperature control. The innovative tube design allows rapid heat transfer to the entire PCR reaction. This reduces hold times at the set temperatures while assuring complete PCR.
The Zulu RT was designed by researchers, for researchers, to overcome the limitations of available instruments – with a key motivator of enabling laboratory professionals to perform multiple rapid PCR reactions without sacrificing accuracy or sensitivity. By allowing several users to work simultaneously and perform four reactions at once, the Zulu RT significantly increases the efficiency of the laboratory workflow.
But it’s not just pathologists who will benefit from this innovation – its rapid turnaround times will allow assay developers and researchers to quickly determine the optimal reaction conditions for their tests and publish their results faster. Developers will be able to bring their tests to market sooner, which will help the ultimate end user – the patient.
With the Zulu RT, Streck believes it has developed a unique solution that will redefine the PCR testing landscape and address key challenges faced by labs around the world. By enabling labs to get more data out of their day through a streamlined workflow, tasks from assay development to processing sample backlogs will no longer be limited by daily run restrictions.
MAGNUS: Achieving Automation Through One-Step Tissue Processing And Auto-Embedding
Milestone’s technology offers a groundbreaking solution to increase productivity, efficiency, and patient safety
Milestone’s game-changing innovation, MAGNUS, is a rapid, automatic tissue processor. The goal? Enhanced throughput, which it achieves with dual robotic arms that simultaneously perform two crucial steps in biospecimen histological preparation: tissue processing and embedding. Empowered by Milestone’s Synergy, an auto-embedding rack system with dedicated molds and pads, batches of small biopsies can be processed and embedded in as little as 90 minutes. MAGNUS automatically detects when a Synergy rack is loaded into one of the two retorts and selects the auto-embedding processing programs. As the cassette rack automatically moves to the wax retort, a new rack can be loaded in the first retort and a new program started. With continuous, rapid processing cycles, MAGNUS works within lean laboratory principles.
MAGNUS’ built-in auto-embedding system reduces the potential for errors during manual embedding, which eliminates the need for time-consuming re-embedding, facilitating a more streamlined workflow that benefits everyone from pathologist to patient.
The MAGNUS tissue processor is not only an effective solution for increasing productivity, efficiency, and patient safety – it also dramatically reduces costs by reducing reagent consumption and avoiding the need for cleaning cycles. MAGNUS is lean and safe by design; processing does not require paraffin transfers, saving time and potential blockages, and xylene-free operation allows long paraffin reuse. Additionally, its integral reagent sensors check alcohol purity before every step.
By combining MAGNUS with Milestone’s auto-embedding method, Synergy, they fulfill the need to optimize the laboratory workflow, offering flexibility, speed, and high throughput – crucially, without compromising on quality or safety.
This is true automation – simple, immediate, and stress-free.
Real-Time Focusing: A Leica Biosystems Breakthrough
The solution to scaling up pathology operations – no matter the laboratory size
Over the last several years, digital pathology engineers at Leica Biosystems have tried many technologies to help achieve highspeed line scanning at 40x* magnification – with some proving more promising than others. But when they took a novel approach to real-time focusing (RTF), they hit upon a breakthrough – and a successful patent application (USPTO patent #9,841,590). RTF has been put to good use – joining an extensive portfolio of Leica Biosystems patents in its next-generation digital pathology scanner: the Aperio GT 450 DX.
RTF uses an imaging line sensor and a focusing line sensor to capture digital images of a slide. While scanning, the focusing line sensor receives focusing data from the tissue; meanwhile, the proprietary algorithms determine the best-focus value in a graphics processing unit in real time. Through a control loop, each best-focus value is fed to the objective position on the fly – allowing continuous image capture at the best possible focus.
By visiting pathologists in high-volume anatomic pathology laboratories around the world, the Leica Biosystems product development team saw firsthand the barriers they faced in scaling up digital pathology operations. A common theme quickly emerged: current technologies’ scan speeds were not fast enough at 40x magnification to keep up with high-volume (over 120,000 slides per year) scanning. If high-volume labs wanted to increase workflow efficiency through digital pathology, they were limited to adopting digital for only one or two organs – for instance, breast or prostate samples. RTF offers the solution to this growing problem – the potential to scale up digital pathology operations even in high-volume labs.
By employing Leica Biosystems RTF, labs can achieve scan speeds at 40x* while maintaining excellent focus on the tissue sample. With continuous loading, no-touch operation, and 32-second scan time at 40x*, the benefit of this innovation is clear: the Aperio GT 450 DX with RTF delivers improved throughputs, reduced turnaround time, and a high-quality image viewing experience to enable healthcare organizations to significantly scale up digital pathology operations – no matter the size of lab or workload – so they can meet ever-increasing demands without sacrificing quality.
*15 mm by 15 mm tissue area
For in vitro diagnostic use. The clinical use claims described for the products in the information supplied have not been cleared or approved by the U.S. FDA or are not available in the United States.
Exploring The Tissue Microenvironment To Uncover Spatial Biology Secrets
Fluidigm systems enable in-depth characterization of tumor microenvironments and offer key pathology research insights
Changing the course of how disease is treated or cured requires a comprehensive understanding of complex cellular phenotypes, their functional states, and their spatial relationships to each other and to other structures in the tissue or tumor microenvironment (TME). Fluidigm’s new AccuLift™ Laser Capture Microdissection (LCM) system – along with the growing use of Imaging Mass Cytometry™ (IMC™) – enables a better understanding of these characteristics based on the pathology and immune response of the TME and the molecular underpinnings of disease.
The AccuLift LCM system integrates slide digitization and a unique cloud collaboration feature to offer laboratories a comprehensive digital research approach. The system also combines patent-pending laser positioning with a streamlined user interface – so, with just a few clicks, the pathologist can precisely capture cells and regions of interest from limited tissue to achieve a better understanding of the heterogeneous TME. The solution even includes a complete reagent portfolio that improves downstream molecular analyses of small samples.
When it comes to IMC, the high-dimensional spatial visualization of the TME provided by the Hyperion™ Imaging System enables research pathologists and laboratory professionals to gain deep single-cell insights to better understand the cell phenotypes and functions present in their samples.
Highly-multiplexed IMC has already been demonstrated to provide an exceptional approach to: i) identifying singlecell signatures in breast cancer that correlate with clinical outcomes (1), ii) gaining novel insights that may aid in the development of new biomarkers and combination treatment strategies to immune-checkpoint targeting in Hodgkin lymphoma (2), and iii) shedding light on lung pathology at the single-cell level through interrogation of the interplay between infected cells and the immune system in COVID-19 (3).
Fluidigm’s AccuLift LCM system and Hyperion Imaging System have become essential tools for clinical researchers who want to reveal how immunotherapy responses and immune cell composition within the TME can be exploited to develop diagnostics, prognostics, and treatments in the future.
Shaping The Present And Future Of Lyme Disease Diagnosis
Gold Standard Diagnostics is leading the way with its Lyme disease portfolio
Lyme disease – a multifaceted disease of the spirochete Borrelia burgdorferi – was first brought to national awareness in the 1980s. Although clinical symptoms continue to be the primary basis for diagnosis, the distinct stages of progression can mimic other diseases – leading to misdiagnosis and failed treatment.
Early diagnostic innovations capitalized on ELISA serological testing to detect and measure immune responses to B. burgdorferi infections. By the 1990s, it became clear that the sensitivity and specificity of laboratory testing needed to improve. Innovative technology rose up once again, with academic laboratories developing the Western blot method to directly observe both specific and nonspecific immune responses. Commercial developers quickly followed suit to create standardized testing and develop the two-tier diagnostic algorithm we still use today.
In more recent years, Gold Standard Diagnostics has been developing innovative technology that is once again shaping the future of testing for Lyme disease. Although the Western blot has served the community well for decades, scientists have capitalized on the development of molecular recombinant techniques to produce and purify the highly specific B. burgdorferi antigens needed for a brand-new approach. Gold Standard Diagnostics is a part of that movement; its Lyme Line Blot offers significant improvements over the Western blot, with increased sensitivity and specificity for consistent, reliable laboratory testing. Next, the company further developed the technology to create Lyme Immunoblot, which also provides easy-to-interpret results. Gold Standard Diagnostics continues to develop both ELISA and Line Blot assays to meet the ever-evolving need for accurate, innovative diagnostics for Lyme and related diseases.
Confirmatory testing for Lyme disease has also continued to evolve; recognizing the need for easier confirmation, the CDC introduced the modified two-tier testing (MTTT) algorithm as an alternative to classic methods. In response, Gold Standard Diagnostics has developed the testing needed for the MTTT with industry-leading proprietary antigens.
In the USA, cases of vector-borne diseases continue to rise and Gold Standard Diagnostics is driven to develop new diagnostic methods to tackle this major challenge. As a market leader for both ELISA and immunoblot assays, Gold Standard Diagnostics will always aim to meet the evolving need for accurate diagnosis of Lyme and other tick-borne diseases.
HALO® Software Suite: From Bench To Bedside
Indica Labs facilitates bench-to-bedside transition of quantitative and deep learning assays in digital pathology
Indica Labs’ HALO® image analysis platform uses computer vision algorithms and HALO AI™ deep-learning networks to enable rapid, quantitative tissue evaluation. Designed around the needs of organizations performing tissue-based research, HALO is the industry standard for biomarker expression profiling, particularly in immuno-oncology. And it has been cited in multiple studies that identify novel spatial immune signatures associated with patient prognosis and immunotherapeutic response (4,5,6,7).
Beyond immuno-oncology, HALO AI has been used to develop deep-learning tools for routine pathology – including tissue classifiers to detect lung cancer lymph node metastases and to differentiate between common gastric injury types (8,9). The potential benefits are clear: improved clinical decision-making, streamlined workflows, improved practice efficiency, and reduced costs. Whereas research and discovery image analysis workflows are flexible and open, clinical assays must be locked down and delivered in an intuitive, standardized format. For assay developers, HALO AP® allows seamless transition of quantitative image analysis and deep-learning assays from bench to bedside. HALO AP’s flexible Assay Builder and intuitive interface enables the user to import novel algorithms built in HALO or HALO AI. The guided, stepwise workflow is designed around these algorithms to make the assay easy to follow and deploy, ensuring accurate and standardized results – even for the most complex assays. After validation, the assays are signed and locked to prevent tampering.
The Clinical Trials module lets the user take full control of their assay during clinical trials and multi-site validation – inviting collaborators, monitoring status, and sharing results with stakeholders. As cases arrive, the workflow guides collaborators through the review process and manages all image analysis and algorithm settings.
For CLIA laboratories wishing to deploy novel quantitative assays, HALO AP can integrate directly with existing laboratory information or image management systems or function as a standalone browser-based image management system with end-to-end case management – from image import to report generation.
Breaking Down Barriers To Digital Pathology
How Corista’s image management platform – DP3 – can help improve clinical review and research workflows
Developed in collaboration with a team of pathologists, DP3 aims to address the complex, competing demands of the modern pathologist. The imaging management platform provides pathologists with a 360° view of their cases and the anatomic pathology workflow by consolidating data and native images into a single dashboard – whether it’s within a single laboratory or across a network of hospitals, laboratory information systems, or whole-slide imaging scanners. Segregating data and repositories between facilities is an integral part of the easy-to-use interface, and pathologists can quickly check and manage their workloads while accepting, reviewing, and transferring cases to their colleagues – regardless of patient or location.
Device interface ergonomics have been a key obstacle to the acceptance of digital pathology. Many viewing methods rely on standard devices – such as a mouse or trackpad – to navigate on-screen slides, which requires highly repetitive hand movements and can lead to rapid fatigue. Understanding this challenge, Corista patented the Virtual Slide Stage (VSS) to eliminate the mouse altogether. VSS requires only one hand to manipulate and view a slide on the platform, which significantly improves the ergonomic efficiency of digital slide viewing to yield the same productivity as standard microscopy.
With a commitment to advancing the adoption and utility of digital pathology, Corista recognized the importance of integration with leading image analytics providers. Today, Corista provides direct access to industry-leading image analysis within DP3, which enables pathologists to receive results from each analysis directly in the case. And that allows pathologists to manage cases quickly and efficiently while ensuring information is securely stored and accessed in one place.
In short, DP3 optimizes the image management workflow – whether the pathologist is consulting on cases, collaborating on research projects, presenting at a conference, or managing quality assurance activities. The scalable, secure platform offers medical centers the flexibility to create a unified digital working environment that promotes collaboration, communication, teaching, and reporting. Corista continues to push the digital pathology market forward, creating innovative solutions for the modern pathologist.
Accelerate Time To Actionable Results With Saphyr®
Next-generation cytogenomics consolidate traditional cytogenetic assays into a single workflow
Despite a sequencing technology-inspired revolution in genomics research and diagnostics, cytogenomic labs’ approach to structural variants has hardly changed. Though next-generation sequencing (NGS) identifies single-nucleotide variants and small (<150 bp) insertions and deletions, it fails to identify most large insertions, deletions, and copy number variations in repetitive regions of the genome. It also does not reliably detect balanced structural variants, such as inversions and translocations. NGS relies on short-read sequences that are mapped to a reference human genome – introducing bias when calling structural variants. In addition, the cost of long-read sequencing is still too high and the throughput too low for routine use.
Current cytogenetic methods, such as karyotyping, fluorescence in situ hybridization, and array comparative genomic hybridization, cannot address complex cases alone because of their technical limitations and need to be combined with molecular methods – such as MLPA, qPCR, or RNAseq – to provide a complete therapeutic and prognostic assessment of the tumor genome.
The Saphyr® system from Bionano Genomics was designed to address these challenges through optical mapping of megabase-sized DNA molecules and studies around the world are confirming its performance. A US study by leading cytogeneticists of 100 patients with acute myeloid leukemia (AML) found 100 percent concordance with traditional clinical cytogenetics analysis. Moreover, Saphyr identified clinically relevant structural variants in 11 percent of cases that had been missed by routine testing and, in 13 percent of cases, it refined the underlying genomic structure reported by traditional cytogenetic methods. In 6 percent of cases with normal karyotypes, optical genome mapping detected cryptic translocations involving gene fusions. Based on their results, they recommend Saphyr to be considered as the first-line test for the detection and identification of clinically relevant structural variants in AML.
Saphyr is the only technology available that consolidates traditional cytogenetic assays into a single workflow. By providing a complete, unambiguous picture of the genome structure, Saphyr can identify prognostic markers that are not currently monitored and enable complete characterization of the cancer or patient genome in a single test.
- HW Jackson et al., Nature, 578, 615 (2020). PMID: 31959985.
- T Aoki et al., Cancer Discov, 10, 406 (2020). PMID: 31857391.
- AF Rendeiro et al., medRxiv, [Preprint] (2020). PMID: 33140072.
- IP Nearchou et al., Cancer Immunol Res, 7, 609 (2019). PMID: 30846441.
- IP Nearchou et al., NPJ Digit Med, 3, 71 (2020). PMID: 32435699.
- A Rasmusson et al., Am J Pathol, 190, 1309 (2020). PMID: 32194048.
- PC Tumeh et al., Nature, 515, 568 (2014). PMID: 25428505.
- HHN Pham et al., Am J Pathol, 189, 2428 (2019). PMID: 31541645.
- DR Martin et al., Arch Pathol Lab Med, 144, 370 (2020). PMID: 31246112.