featuring the Echo® Acoustic Technology119 Total Articles and Other Media
Institution: Labcyte Inc.
Publication: ARTICLE: CIOReview2017 PDF abstract
Liquid handling plays an integral part inthe Biotechnology industry, since a major part of daily lab operations for testing, research, or production relies on the efficient transfer of samples and reagents to designated containers. Traditional liquid handling approaches that use pipettes often cannot achieve required levels of miniaturization, precision, and accuracy, and introduce chances of contamination.
Publication: Science Magazine2017 abstract
If this is the biology laboratory of the future, it doesn’t look so different from today’s. Scientists in white lab coats walk by with boxes of frozen tubes. The chemicals on the shelves—bottles of pure alcohol, bins of sugar, protein, and salts—are standard issue for growing microbes and manipulating their genes. You don’t even notice the robots until you hear them: They sound like crickets singing to each other amid the low roar of fans.
Institution: Columbia University Medical Center
Publication: Nature2017 abstract
Pharmacological and functional genomic screens play an essential role in the discovery and characterization of therapeutic targets and associated pharmacological inhibitors. Although these screens affect thousands of gene products, the typical readout is based on low complexity rather than genome-wide assays. To address this limitation, we introduce pooled library amplification for transcriptome expression (PLATE-Seq), a low-cost, genome-wide mRNA profiling methodology specifically designed to complement high-throughput screening assays. Introduction of sample-specific barcodes during reverse transcription supports pooled library construction and low-depth sequencing that is 10- to 20-fold less expensive than conventional RNA-Seq. The use of network-based algorithms to infer protein activity from PLATE-Seq data results in comparable reproducibility to 30 M read sequencing. Indeed, PLATE-Seq reproducibility compares favorably to other large-scale perturbational profiling studies such as the connectivity map and library of integrated network-based cellular signatures.
Institution: Labcyte Inc.
Publication: ARTICLE: DDNEWS2016 abstract
There are people who will die of cancer this week even though there are drugs that could help them.
At the same time, hundreds of patients will undergo cancer chemotherapy that, while debilitating and expensive, will not cure them of their disease. While cancer is a formidable foe, there is a way to improve patient care and prognosis immediately.
Researchers in Finland, Sweden and Spain have modified ex-vivo testing of cancer cells with significant results. Their approach is far more “personalized” than traditional precision medicine. Their results are striking. They provide a missing link between genomics-based mutation determination and clinical efficacy. Precision medicine (also referred to as “personalized medicine” or PM) appears to many patients, doctors and researchers to be a golden highway from disease identification to cure. The idea of interrogating the genome of a particular cancer to determine its Achilles heel is intuitively satisfying and understandable. There are, however, significant problems. First, PM is neither personalized nor precise. PM strives to identify the appropriate biomarker (usually a DNA mutation but proteins, peptides and metabolites can stand as biomarkers as well) to categorize the patient as a member of a specific group of patients. The patient is treated with a drug that has shown positive results on previous members of the group. In other words, personalized medicine is actually population-based medicine.
Institution: Massachusetts Institute of Technology (MIT)
Publication: ARTICLE: DDW2016 abstract
Christopher Voigt is a professor of biological engineering at the Massachusetts Institute of Technology, where his lab focuses on synthetic biology. Two major areas of interest for him are developing a genetic programming language for cells and applying synthetic biology to biotechnology challenges. Ultimately, Voigt aims to design whole genomes for applications from agriculture to medicine. DDW chatted with Voigt to learn more about the impact this field will have on pharmaceutical workflows and drug pipelines.
Publication: ARTICLE: IN VIVO: Business & Medicine Report2016 abstract
A handful of academic groups in Europe and the US are using high-throughput (HT) ex vivo screening to test the sensitivity of individual patient tumors to hundreds of combinations of cancer drugs - a strategy that in earlier iterations failed to predict response to therapy. HT screening is used routinely in drug discovery. Thanks to advances in nanoliter-scale sample handling and computational biology, evidence is slowly building the potential of HT approaches to identify novel combination therapies, first in leukemia and hopefully for treating other cancers.
Institution: Labcyte Inc., BMG LABTECH, and Cisbio
Publication: POSTER2015 PDF abstract
Epigenetics continues to emerge as an important target class for drug discovery and cancer research. As programs scale to evaluate many new targets related to epigenetic expression, new tools and techniques are required to enable efficient and reproducible highthroughput epigenetic screening. Echo liquid handlers can transfer compounds, samples, and reagents in sub-microliter volumes to high density assay formats using only acoustic energy - no contact or tips required. This eliminates tip costs and reduces the risk of reagent carryover. The PHERAstar FS multi-mode plate reader, with the highest sensitivity and lowest read time of assays in high density plate formats, is a perfect complement to enable an unparalleled solution for cost-effective, high-throughput epigenetic screening. Using the HTRF EPIgeneous™ Methyltransferase kit from Cisbio, we developed a miniaturized methyltransferase assay that can be easily adapted to automation and increased throughput, while maintaining high data quality. HTRF assays are typically performed at volumes of about 20 µL in a 384-well low volume plate. However, with the nanoliter dispense increments of the Echo liquid handler, assay volumes can be reduced significantly while maintaining data quality. In this study we were able to reduce a methyltransferase assay to a 2 µL final volume with excellent results.
Institution: AstraZenenca, Cambridge, UK
Publication: SLAS 20152015 abstract
The high throughput direct measurement of substrate-to-product conversion by label-free detection has been considered the “Holy Grail” of drug discovery screening. Mass spectrometry as a detection system has the potential to be part of the ultimate screening solution. However, MS with existing sample introduction modes, despite being widely used in drug discovery typically cannot meet the throughput requirements of HTS. We propose a unique, innovative solution to the problem of throughput by using acoustic droplet ejection (ADE) to transfer femtoliter samples from microliter assays rapidly, precisely and accurately directly into a mass spectrometer. Acoustic technology has been widely used to support compound management activities within the pharmaceutical industry. The speed, accuracy, precision and robustness of acoustic dispensers have been proven. In principle, the integration of an acoustic source with a MS detector would result in a system capable of delivering ~4000 data points per hour into a high sensitivity label-free detector. It would enable sampling from 1536-well plates and reduce the total required assay volume to <5µL. The rapidity of sampling would enable real-time kinetic studies to capture multiple data points within the first minute of initiating a reaction. Together Labcyte Inc, Waters Corp and AstraZeneca have built a prototype acoustic source linked to a mass spectrometer. Droplets in the range of 50-200fL are acoustically ejected directly into the MS through a charge field. The ion beam is detected in the single quad MS where the typical signal has a very sharp attack profile and instant stop when the acoustic spray is turned on and off. This process produces a square wave signal which is simple to integrate for quantitative assays, and generates reliable and reproducible spectra. The system works in both positive and negative ion modes. The process is capable of producing singly or multiply charged species. The ability to load samples into a MS detector at such a high rate from much reduced assay volumes has significant potential not only within drug discovery but other areas of industry. Dynamic fluid analysis, the ability of the acoustic injector to adjust automatically to varying viscosities and surface tensions of the sample, allows the generation of droplets from a wide range of fluids including blood, plasma, cell culture medium, acid digests, and chemical syntheses. In principle, the simplicity of the acoustic source enables it to be fitted to any type of MS detector with an atmospheric pressure interface (single quad, triple quad, ToF), extending the range of applications into the “omics” field.
Institution: Labcyte Inc., BMG LABTECH, and Cisbio
Publication: POSTER2015 PDF abstract
Acoustic liquid handling utilizes high-frequency sound waves that are focused on the surface of a fluid to eject nanoliter-scale droplets with high accuracy and precision. The Echo® 525 liquid handler increases the transfer droplet volume 10-fold over our Echo 55X products, which allows for transfer rates of up to 5 μL/s and enables workflows for life science applications that were previously less practical. To enable the transfer of larger volumes of fluid at this faster transfer rate we are releasing a companion consumable, the multi-well Echo Qualified Reservoir (ER). The ER is a 2x3 well, ANSI/SLAS compatible source plate that has a maximum starting volume of 2800 μL of fluid per well and a dead volume of 250 μL per well – a large advantage over our standard 384-well plate (Figure 1).
In this work, we showcase two patented Labcyte technologies, Dynamic Fluid Analysis (DFA) and a high voltage (HV) grid, and describe how they enable the transfer of nano- to milliliter volumes of fluid using acoustic droplet ejection (ADE). We utilize a high speed, side-view camera that is coupled with the Echo to capture droplet dynamics in flight (Figure 2), and show how DFA and the HV grid are critical technologies for larger volume acoustic liquid handling.
Institution: Labcyte Inc. and IntelliCyt
Publication: POSTER2015 abstract
The need for characterizing apoptotic processes occurs throughout the drug discovery process – from primary screening to toxicity profiling. Apoptosis is a tightly regulated cell death program that can be executed by cells that are no longer physiologically necessary. It is often triggered as a response to extrinsic factors or inhibited for survival as in the case of many cancer cells. Cell death cascades are complex and dynamic, underscoring the importance of a multi-parametric approach to assess apoptosis. This underscores the need to conduct robust and reliable cellular assays at high densities and with small sample sizes. As such, technological advancements such as High Throughput Flow and low-volume liquid handling have become critical components of methods assessing apoptosis. Using the IntelliCyt iQue Screener HD and MultiCyt® 4-Plex Apoptosis Screening Kit in conjunction with the Labcyte Echo series of liquid handler, we were able to simultaneously detect 4 different apoptosis endpoints in Jurkat cells in both 384- and 1536-well formats.
In this study, Jurkat cells were treated for 24 hours with known apoptosis inducing agents: staurosporine, nocodazole and camptothecin. After treatment, cells were labelled for one hour with a no-wash / single step addition of fluorescent markers for caspase 3/7 activation, Annexin V binding, cell viability, and mitochondrial membrane depolarization. Sub-microliter volumes of compounds and dye were transferred to the 384- and 1536-well cell plates with the Echo 555 liquid handler. The results show equivalent potency estimates for the compounds tested in both plate formats and correlate to previously reported activity for the biomarkers measured.