Echo® 500 Series Liquid Handlers

Serial microsampling of animals reduces the overall number of animals sampled and euthanized for toxicology studies. Traditional composite studies in mice can require up to 700 μL of blood for each time point in a pharmacokinetic study. A draw of 700 μL from a mouse would require the animal to be euthanized and often require the use of addition “satellite” animals to complete the study. Thus, in a 9-point time course analysis of mouse plasma, nine mice would be sacrificed. In response to programs like the EU 3Rs initiative to reduce the use of animals in research researchers have turned to microsampling as an alternative to composite studies. With advances in bioanalytical techniques drug levels can be determined from samples of 20 μL or less. This small sample volume or microsample enables reduces the dependency on satellite animals to complete a study. Additionally, microsampling is faster and less stressful than traditional composite studies.

Phosphoinositide 3-kinase alpha (PI3Kα) is frequently implicated in human cancer because of its role in the induction of cell proliferation and survival and is highly sought after as a drug development target. High-throughput screening efforts to identify inhibitors of PI3Kα have been widely conducted in the pharmaceutical industry. Compounds identified from high-throughput screening efforts for various targets in the PI3K pathway have developed into potential anti-cancer drugs. The ongoing need to reduce screening costs has led to the growing trend toward miniaturization. The Echo series of liquid handlers combined with the newly released Echo qualified Reservoir affords a reduction in transfer volume of both compounds and bulk assay reagents while increasing throughput and maintaining data quality. This application note describes a fully automated approach utilizing the Labcyte Access Workstation to integrate both the Echo 525 and Echo 555 liquid handlers on the same workstation to facilitate assay execution in the identification of potential PI3K inhibitors

The study of protein function relies upon recombinant gene assembly for protein expression and functional assays. This strategy is particularly important when available information regarding function is limited. The vast amount of data generated from genome sequencing projects has paved the way for diverse functional genomic studies that involve cloning, modification and subsequent expression of target genes. This requires flexible and efficient procedures for generating vectors containing gene fusions, gene variants, genetic coding for protein tags and cellular targeting. Furthermore, efficient high throughput cloning and gene assembly procedures are essential for interrogating signaling pathways with multiple gene constructs. The resulting gene constructs can be analyzed in stable transgenic or in transiently expressing biological systems. This application note demonstrates an efficient and robust gene assembly method to generate a fusion protein for functional cellular assays.

The phosphoinositide-3 kinase (PI3K)/AKT signaling network is one of the two most commonly mutated pathways identified in human cancers and the most frequently mutated pathway in breast cancer. Somatic alterations including PIK3CA mutations are the most common genetic alteration of this pathway; 80% or more occur within the helical (E542K, E545K) and kinase (H1047R) domains of p110. Such mutations confer increased catalytic activity for the generation of the second messenger phosphatidylinositol (3,4,5) - triphosphate (PIP3) and downstream pathway activation to induce cell proliferation, survival and potential tumorigenesis. These mutations can also confer resistance to therapeutic intervention. Identifying acquired mutations, not present in normal patient tissue, in tumor derived material, including CTC’s and DTC’s, is important to diagnostic redisposition testing for cancer, prognosis and can ultimately inform targeted therapy. This application notes demonstrates a highly efficient, low-cost assay platform to detect PIK3CA somatic mutations.

Class I Phosphoinositide 3-kinase (PI3K) proteins have been extensively characterized with respect to their roles in cell proliferation and tumorigenesis, and therefore serve as desirable targets for oncogenic drug development. Class I PI3K isoform-specific inhibitors provide elucidation of the individual isoform functionality, and the dependence particular cell types have on it. In this application note, the impact of PI3K isoform-selective inhibitors on the viability of PC3 and MCF-7 prostate cancer cells is evaluated.

Learn how scientists at the Institute for Molecular Medicine Finland investigate individualized treatment for drug-resistant acute myeloid leukemia with the help of Labcyte Inc.’s Echo® liquid handler.

Epigenetic processes are attracting considerable attention in drug discovery as their fundamental roles in the regulation of normal cell development and contributions to disease states become more clearly defined. Histone methyltransferases (HMTs) are high interest drug targets as histone methylation is linked to certain disease states, including a wide variety of cancer types. This application note demonstrates the utility of the Echo series of acoustic liquid handlers toward developing G9a histone methyltransferase (HMT) assays in a parallel, streamlined and automated workflow.

The Phosphoinositide 3-kinase (PI3K) pathway has been studied extensively for its role in the development of human cancers. Tools to detect the regulatory impact of PI3K inhibitors on pathway activation have become essential for drug developers. Indication of pathway activity may be derived from the detection of phosphorylated pathway members downstream of PI3K. In this application note, the levels of phospho-Akt are quantitated with Cisbio’s HTRF Cellular Assay kit.

Advances in whole-genome amplification have enabled sequencing of DNA and RNA from a single cell, or what is commonly called Single-cell Genomics (SCG). However in a recent Nature Protocols article, researchers at the Department of Energy Joint Genome Institute describe an approach that can meet the throughput and sample quality required for robust whole genome amplification from a single cell. This application highlight, describes the role of the Echo liquid handler in this new approach.

This poster showcases two patented Labcyte technologies, Dynamic Fluid Analysis (DFA) and a high voltage (HV) grid, and describes how they enable the transfer of nano- to milliliter volumes of fluid using acoustic droplet ejection (ADE). A high speed, side-view camera that is coupled with the Echo to capture droplet dynamics in flight is used to show how DFA and the HV grid are critical technologies for larger volume acoustic liquid handling.

Dr David Simpson, Senior Lecturer at Queen's University Belfast, reveals the main advantages of acoustic liquid handling for his research into cardiovascular disease and diabetic complications.

Dr Allan Jordan, Head of Chemistry, Drug Discovery Unit at the Cancer Research UK Manchester Institute and Chris Grimley, Vice President of Marketing at Labcyte, share their thoughts on winning the Scientists' Choice Award® for Most Successful Video of 2015. Watch the winning video here.

Dr David McClymont discusses automated approaches to DNA assembly used at Imperial College London

Glitzy awards ceremony sees SelectScience present Seals of Quality to more top-rated laboratory products

Labcyte Inc., Wyatt Technology Corp., Erlab Inc., Specac and Bertin Instruments among the recipients as more top-rated products gain a coveted SelectScience Seal of Quality