Diseases like cancer have complex tissue morphology requiring microscopic examination.  Typically this involves 2D examination through a microscope by a pathologist, a slow and manual process and doesn't reveal 3D structures.  3D serial section microscopy has proven to be a powerful tool in examining the 3-dimensional nature of tissue; however, it is limited by the size of tissue samples that can be used and the manual process of acquiring data.

The Knife-Edge Scanning Microscope (KESM) acquisition and analysis computational system resolves these issues by providing high resolution light microscopy image data at multi-cubic centimeter scale. Using this system for quantification of microvasculature provides the ability to examine, measure, and compare the 3-dimensional nature of vascular networks at whole organ scale and sub-micron resolution.

Open Targets is a public-private partnership made up of four global leading institutions in the fields of pharmaceuticals, bioinformatics and genomics, GSK, EMBL-EBI, the Wellcome Trust Sanger Institute, and Biogen. We combine large-scale genomic experiments with objective statistical and computational techniques to identify and validate the causal links between targets, pathways and diseases. We have designed and developed the Open Targets Platform, a web application for data integration and visualisation, which supports both target- and disease-centric workflows. Our Platform enables biomedical researchers to discover and prioritise biological targets for new therapies. Targets may be a protein, protein complex or RNA molecule, and we integrate evidence through the target gene. Phenotypes and diseases are integrated through the Experimental Factor Ontology, so that we can include both Mendelian (rare) and common diseases and their phenotypes. We derive evidence of association between a target and a disease from multiple public domain resources, including germline and somatic genetics, known drugs, differential gene expression profiling, reaction pathways, murine genetic models and the scientific literature. We also provide an association score, which takes into account the observed frequency, the experiment confidence, and the likely strength of the effect of the target on the disease. By drawing on expertise in product and platform development including product testing, UX design and site development, we have created this comprehensive and robust data integration for access and visualisation. In addition, programmatic retrieval of data via REST services is also available as well as dumps of our entire datasets. In this talk, I will introduce the Open Targets Consortium and focus on our Open Targets Platform. I will demonstrate how the Platform can be used to visualise and interpret target and disease associations based on the different datasets available.

Carlos Olguin will talk about LogicInk's ongoing efforts around electronics-free temporary tattoo-like devices. These devices transform in shape or color to convey useful information about a wearer's body and surrounding environment. 

LogicInk has established an exceptional, multidisciplinary team that is pioneering new chemical and biological materials and their potential applications for temporary tattoo-like devices. Carlos has considerable epxerience in co-creating applications driven by programmable materials, in part, during his tenure at Autodesk, where he founded and led the Bionano Research group.

The nature of work in the clinical core lab has changed over the years from beakers of liquids, specimens and compounds on countertops to sophisticated equipment with prepackaged reagents and electronic services and software packages. Because the testing technology and environment has changed, the response to flexibility needed to change.  Culminating with its openning in 2015, Geisinger Medical Laboratories had the opportunity to design and build a new Laboratory Medicine Building.  Early in the design phase, it was deemed critical to identify the factors driving practice change and incorporate lab-based solutions to address these factors.

The commercialization of micro and nanofluidic devices has had promise for providing novel solutions to deliver high throughput, more efficient, integrated biological and chemical analysis tools.  This presentation addresses the commercialization perspectives of integrating on the micro and nanoscale acoustic droplet ejection (ADE) for high throughput (HT) applications with mass spectrometry (MS) and gel electrophoresis (GE).

First highlighted are the physical principles of ADE and the key technologies that enable robust acoustic liquid handling operations—namely the ability to: probe the properties of the fluid; adjust in real-time to account for dynamic surface tension and viscosity variations, determine the acoustic energy required for ejection; and to impart charge on the droplet to aid in droplet transfer.

Next, we explore the commercialization perspectives for HT applications in different modalities to explore directly acoustically loading samples into MS, enabling true HT screening in a label-free format, and to explore the low volume transfer of proteins in solution into a microfluidic gel device for a GE assay.  For the GE assay, we demonstrate 100 nL per well transfers of free antigen-binding (FAB) fragments in solution; Kd is extracted; and >80% improvement in assay precision and throughput compared to manual operation.

In conclusion, commercialization perspectives are addressed with these high throughput applications with ADE and the need to integrate “big data” collection to support further HT applications in the development of microfluidic devices.

The Instrumentation Group at the BC Cancer Agency’s Genome Sciences Centre (GSC) is unusual in having an engineering group and extensive prototyping facilities embedded in a biomedical research and clinical cancer treatment facility. The group has completed numerous pipeline-specific automation projects, and in one case, enabled the GSC to participate in a major international consortium based on our in-house technology. In-house solutions range from simple manual devices to components integrated with liquid handlers, to full robots as well as ongoing programming of the GSC’s liquid handlers. This presentation will highlight significant projects and some lessons in efficient prototyping and good software practices that have been learned.

The group’s primary role is programming the GSC’s commercial liquid handling robots, working closely with our methods development, quality assurance and production teams. This joint approach, with expert molecular biologists working in tandem with expert programmers and independent QA, has produced robust methods for a variety of sample types. In fact, we have harmonized chemistry and liquid handling protocols to the extent that nine different NGS library types (PCR-free gDNA, FFPE DNA, RNAseq, CHiP, Bisulfite Seq, (exome or other) capture samples and circulating cell free gDNA) run under one main program. This has substantial advantages but also potential pitfalls, which will be described.

Drug development is a costly and time consuming process, poor translation of data from pre-clinical studies to the clinic is a major contributor as late-stage drug failure is very expensive. Testing drugs in 3D tissues that better represent human organ physiology and function may help reduce the cost of drug development by improving translation to the clinic. 

In order to mimic the complex heterogeneity and microstructure of tissue, we are developing a novel 3D bioprinting paradigm called Lab-on-a-PrinterTM (LOP). The LOP concept involves integration of microfluidic liquid manipulation directly with filament deposition technology, this enables rapid switching between different cell-containing bioink compositions and the ability to multiplex several materials in a single printhead.

The LOP platform technology is capable of generating multi-material cell-loaded 3D hydrogel constructs using fused filament fabrication (FFF). Our system uses co-axial flow focusing, a process whereby cells within printed fibres are protected from the damaging shear forces present in many alternative bioprinting strategies. We are thus able to use LOP to generate fibres with very high cell density while printing at high fibre speeds without sacrificing cell viability. 
The LOP system can generate fibres containing a variety of extracellular matrix factors, growth factors, cytokines, and other bioactive compounds. The user can customise bioinks to optimise the cellular microenvironment in a region specific way within a single tissue construct. 

I will discuss how Aspect and our collaborators are using the LOP technology to generate a variety of unique functional 3D human tissues for use as pre-clinical testing tools in indications such as asthma, hypertension, premature birth and neurodegenerative disease. Printing tissues on demand will have significant impact for regenerative medicine, I will describe how LOP technology is being used to develop implantable orthopaedic tissues to improve quality of life for patients with joint injuries.
 

R&D in life science, material science, and chemistry is burdened by fragmented and unstructured data (“spreadsheet hell”), and ambiguous or unrecorded methodological data. This leads to low-confidence decisions, wasteful rework, missed observations, and delayed or failed technology transfer across sites or scales of development.

“Data science” and “big data” tools are often hailed as a solution to these problems.  But statisticians and data scientists spend more time gathering, cleaning, and linking data than actually learning from it. The ability to “clean-up” data is impaired by the dynamic nature of R&D processes, the heterogeneity of data sources, and the complexity of modern R&D organizations.

Riffyn’s cloud-based software platform uses visual process design and integrated data analytics to solve these problems. Riffyn collects data from people, instruments and databases, and uses the process design to contextualize the data the moment it is generated. It then uses the process design to automatically summarize and join all that data into standard tables for rich statistical analysis, visualization and machine learning — allowing users to instantly answer questions of cause-and-effect across traditional silos of team, place and discipline.  Thus by simply creating a process and experiment design with Riffyn, scientists and engineers have effectively architected their own vertically-integrated data system (front end, database, & ETL) in less time than it would have taken to communicate their data requirements to IT.

With built-in versioning, Riffyn is also continuously adapting — so that laboratory methods, data and, analysis are always in sync with ever-changing R&D processes.  This frees each organization’s IT team to attack the backlog of high-value analytical and business intelligence projects that are usually sidelined by the heavy burden of core system maintenance. No longer will database development or data integration be a drain of precious IT resources, nor a bottleneck to scientists and engineers who are trying to improve their R&D processes.

The result is a new level of transparency and confidence in R&D decisions, a culture of continuous improvement, and corresponding gains in R&D effectiveness.

A hardware architecture was developed specifically to facilitate collaborative development and dissemination of microfluidic experiments. Modular pressure regulators, incubators, and chip-to-world interfaces can be readily customized and 3D-printed by investigators. The architecture supports a range of experiments with both whole-organisms and single cells. Wide-spread adoption of a common, community-developed hardware platform for biological experimentation will propel large-scale collaborative efforts and accelerate scientific breakthroughs.

Those that fund and publish scientific data are actively proposing or requiring strategies to improve research conduct in the hopes of improving research outcomes and scientific deliverables. Early responders to research reproducibility concerns are rightly focusing on study design, statistical approaches, characterization of critical reagents and attention to bias and research premise. While these measures are promising, they will likely fail to address the risk associated with inconsistent research data management and record keeping that is typically unaddressed in our research training
programs.

Research Quality Assurance (RQA) systems are used to monitor and support the processes by which scientific data are generated and managed. Quality systems provide assurance through the generation of credible evidence (documentation) that data are fit for their intended purpose and that the processes under which they have been generated can be reconstructed through effective record keeping. Responsible agencies mandate robust research QA systems in formally regulated research environments as a way of supporting data reliability and transparency. However, scientists are not typically implementing RQA systems within basic research settings because RQA training and expertise is rarely available to guide the implementation and use of quality management systems. This is unfortunate because the adoption of RQA best practices has been recommended for years (Volsen SG Kent JM, et al. 2004. Drug Discovery Today.9:21;903-905; WHO. Quality Practices in Basic Biomedical Research. World Health Organization. Geneva, Switzerland: WHO/TDR) as a reasonable strategy for supporting research quality.

Biomedical research scientists must be prepared to demonstrate the quality of their data to ensure that their work stands the test of time and advances human, animal or environmental health. In addition, trainees deserve to leave our institutions prepared to transition into careers where a seamless integration into a QA environment is expected. This presentation will provide an introduction to research quality assurance as a strategy for addressing known threats to research quality. It will also encourage scientists to promote scientific excellence, improve research training, and stand up for the quality of their work by introducing RQA best practices into their individual, collegiate or institutional
research settings.
 

The consistent and optimized production of living human cells for drug discovery and regenerative medicine faces many challenges including the need for cost effective large scale expansion, improved representation of in vivo cellular physiology, and the ability to achieve reproducible data and/or cellular products.  In order to achieve these goals there has been an evolution in the methods used to culture cells involving the use of 3D approaches that include the growth of cells in and on biomimetic substrates, optimization of cell culture media, and exposing cells to shear forces and oxygen tension that more closely mimics the in vivo environment.  In addition, in order to make these new 3D processes more cost effective there is an increasing interest to fully automate the cell culture process.  However, many new in vitro 3D cell culture methods, which provide improved physiologically and biologically relevant cellular phenotypes neither lend themselves to automation nor allow the process to be scaled for large cell biomass production.  We have designed and are building a fully automated 3D cell culture robotic system that allows for parallel or random access processing of many cell lines each sourced from unique individuals.  This next generation cell culture robot will allow cell based assays on biologically diverse populations of cells in order to test lead compounds for their biodiverse effects (varying effective doses and toxicology).  

This presentation will discuss the current 3D cell culture systems and their suitability for automation.  Data will be shown demonstrating the benefits of each automated 3D cell culture process in terms of cell morphology and function. Each system will be evaluated for its cost/benefit in terms of biological relevance, yield, and quality metrics. Modern 3D cell culture techniques will be objectively discussed in the context of creating improved standards for primary/stem cell production and screening.

I’ll talk about Strand NGS Server, our server-client NGS offering. Strand NGS server is geared towards small-to-medium scale clinical labs with high-volume sequencing throughputs and low turnaround times.

The talk is in three parts. The first part describes how Strand NGS Server marshals the various computational resources available to a typical clinical lab. It also discusses the primary advantage of Strand NGS Server over its desktop counterpart: namely, collaboration.

The second part describes the ease of setting up a given pipeline in Strand NGS server, and speaks of four examples, each corresponding to a different clinical panel: germline, somatic, clinical exome and rare diseases.

The last part describes a day in the life of a bioinformatician, and goes over a few typical use cases of Strand NGS Server.

Gain insights into T-cell expansion, viral vector production and scaling production of mesenchymal stem cells (MSCs) through the use of a functionally closed, automated, cell culture process.

Dr. Beltzer (Terumo BCT, CO, U.S.) will present a number of case studies to describe how process development and economic goals were achieved in both industry and academic settings. Results include up to a 500-fold expansion of T-cells in 12 days, 40 percent reduction in cost of goods (COGs) of growing cells for an allogeneic therapy, and automated viral vector production with titers similar to flask-based processes. Particular attention will be directed toward the process changes often needed to meet these goals.

This seminar will give attendees a full overview of two new Miltenyi cell sorting platforms, the MultiMACS X and the CliniMACS Prodigy and how these instruments can be used in various primary cell assays to speed-up time to data.  These platforms offer fully automated cell sorting at throughputs and scales not previously possible using traditional sorting platforms (MACS or FACS).   We will specifically investigate how these platforms can reduce assay time in the phenotypic analysis of mouse tumor infiltrating leukocytes (TIL) and also generate sufficient numbers of primary human immune cell subsets to enable high-throughput primary cell screens.  Finally, we will introduce the MACSQuant X, a high-throughput flow cytometer, that can be leveraged in conjunction with the MultiMACS X and/or CliniMACS Prodigy to enable the rapid analysis of primary cell populations in a 384 well format.     

Acoustic dispensing technology has allowed for compound plating to be highly customizable depending upon scientific needs.  The ability to dispense compounds from a single well to any well of a destination plate has made plating drug combinations a possibility. At NCATS, we have applied acoustic dispensing technology to create drug combination matrices, grids which contain combinations of 2 compounds at variable ratios to allow for exploration of drug synergy.  This technology required significant in house software development and integration with our existing robotic infrastructure. We now have applied this technology to drug repurposing projects for treating cancer, malaria, ebola virus and zika virus, which has been included in publications and provided the basis for ongoing clinical trials.

Often we are concerned at the thought of a lab run by robots, not humans-- but what if instead of having the world's brightest minds concerned with pipetting, blotting and scanning, there was a lab-bot to take care of basic lab routines, analyze data and order product? The bright minds now can spend time on critical thinking, expanding projects and networks.

Whether you fear it or embrace it, a robotic revolution is happening. Be a part of it and meet the inventor of a automation device so innovative, it may just be from the future.

LabBot3D becomes your best friend

Real-time data collection and cloud reporting Multi-functions including: Array printing; liquid handling; scanning; 3D printing
Innovation platform can be programmed to your needs and beyond.

See the presentation, get an in-person demo, share thoughts, and network with the innovation community.

Robots & Research Series: Meet LabBot3D, your new best friend