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Dr. Harry Whitwell
Lecturer, Imperial College London
“We like the Andrew+ Pipetting Robot for automating routine sample prep and also for it being flexible enough for sharing across the lab and to applying to dynamic situations where you need to build new methods quickly for something that you might need to do.”
When Dr. Harry Whitwell, Lecturer, Imperial College London, was recruited to lead the integration of Proteomics at the National Phenome Centre (NPC), he knew that he would have to address a key bottleneck that he would be faced with: sample preparation. Funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR), NPC is a world-class research institute that is focused on advancing metabolic phenotyping research to drive progress in Translational Medicine. When Dr. Whitwell announced that he had recruited a brilliant fellow by the name of Andrew to address NPC’s sample preparation challenges, fellow scientists at Imperial College were keen to meet their new colleague.
They were quite surprised to learn that their new colleague was not exactly a colleague, in the traditional sense. Andrew+™ is a pipetting robot that can prepare samples for many routine laboratory assays, leveraging electronic pipettes along with many connected devices such as fully automated Solid Phase Extraction (SPE) devices, heater-shakers, and magnetic bead separation devices. Unlike graduate students and research associates, the Andrew+ Pipetting Robot never tires, bores, or dispenses the incorrect volume of a reagent from the electronic pipettes that it handles. While most laboratory robotic platforms require an in-depth knowledge of a programming language such as Python, there is no such barrier to building and execute laboratory protocols using the graphical drag-and-drop functionality within the OneLab™ Software that controls Andrew+. However, writing an entire protocol is usually not necessary, as the OneLab Protocol Library contains many ‘click-and-execute’ protocols that can be used with little or no modification and that integrate seamlessly with Waters HPLC, UPLC™, and LC-MS instruments.
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“Alongside wanting throughput and sample reproducibility, we also wanted to be flexible in experiments that we can support. The Andrew+ fits into our pipeline in a few different ways,” commented Dr. Whitwell. Flexibility was a very important parameter for Dr. Whitwell when he was evaluating robotic platforms as the focus at NPC prior to his arrival was on profiling small molecules and lipids from biofluids, tissue extracts, and cell culture. “Rather than thinking of small molecules, lipids, and proteins as distinct modalities, we can combine them from experimental design all the way to data analysis. That is one of our ambitions,” added Dr. Whitwell.
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“One of the really nice features about the Andrew+ is the customer support. There are always people available who can help quite quickly if you need help setting up a new method by using the embedded chat feature within OneLab Software,”
A collaboration with Dr. Johanna Jackson, Department of Brain Sciences, Imperial College London utilized the Andrews+ for automating and streamlining sample prep for proteomics of Alzheimer’s Diseased-brain. While working at Eli Lilly, Dr. Jackson studied synaptic changes and other disease processes in pre-clinical models of Alzheimer’s Disease. Upon returning back to Imperial College, Dr. Jackson led the UK DRI Multi-‘omics Atlas Project; an open resource mapping the cellular pathology of Alzheimer’s Disease, integrating data from Genomics, Transcriptomics, Proteomics and Immunohistochemistry.
Alzheimer’s Disease, the main cause of dementia, impacts approximately 7 million people in the United States [1] and is rapidly becoming one of the most costly, lethal, and burdening diseases of the current century [2]. From a pathological perspective, Alzheimer’s Disease is characterized by the deposition of Aβ plaques and neurofibrillary tangles that are located predominantly in the neocortex and hippocampus. It is hypothesized that the accumulation of Aβ plaques triggers a cascade of harmful events, eventually leading to neuronal dysfunction.
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In recent years, there has been an increasing focus on the role that the glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, play in the pathogenesis of Alzheimer’s Disease. Dr. Jackson’s research applies a multi-omics approach to elucidate molecular signatures in the brain associated with accelerated cognitive decline in Alzheimer’s Disease. The ongoing study has involved the processing of >300 samples from post-mortem brains (middle temporal gyrus (MTG), somatosensory cortex (SOM)). The use of the Andrews+ reduced batch effects during sample preparation and supported non-specialist proteomics scientists to contribute to sample preparation, from protein extraction up to MS-ready sample.
“Andrew+ played a pivotal role in driving this research forward,” added Dr. Whitwell.
The Imperial team leveraged the flexibility of Andrew+ in accommodating different assays with its interchangeable deck layout and ability to move labware around to suit the experiment at hand. Dr. Whitwell further added said Dr. Whitwell. “Andrew+ played a pivotal role in driving this research forward,” added Dr. Whitwell.
One key finding was that protein markers associated with alterations of the astrocytes were found to be most strongly associated with accelerated cognitive decline. This insight may someday lead to the development of new drug targets that could substantially slow the progression of Alzheimer’s Disease in the future. The importance that state-of-the-art, robotic sample preparation plays in such studies is often overlooked.
References:
- Alzheimer’s Facts and Figures Report | Alzheimer’s Association
- Scheltens, Philip, et al. “Alzheimer’s disease.” The Lancet 10284 (2021): 1577-1590.
- Schneegans, Eleonore, et al. “Integrative multi-omics reveal glial signatures associated with accelerated cognitive decline in Alzheimer’s disease.” medRxiv (2024): 2024-08.