The repeatability problem

A few years ago, the US$1.6-million Reproducibility Project: Cancer Biology set out to repeat key experiments from 50 high-profile cancer papers. Its aim was to assess the extent to which published results can be replicated. The project ended up stopping at 18 papers.

The main reason for this was the difficulty of working out what exactly was done in the original experiments. Protocols — precise step-by-step recipes for repeating experiments — are missing from published research more often than not. Indeed, even the original researchers can have trouble pinpointing particulars years later.

The challenge of effective dissemination of research

Repeating the step-by-step execution of an experiment is never easy. Firstly, you need to extract the details from another researcher’s published work. This work hopefully shares everything you need to know in its ‘methods and materials’ section. Then you have to assume that any differences in lab-ware used will not result in differences to experimental outcome. Unfortunately, it still relies on a degree of ‘interpretation’ regarding the way in which a particular step should be implemented by the researcher. For example, can we assume that every researcher uses a pipette in exactly the same way? The answer is, ‘no’, we absolutely cannot. Our intuitive lab software takes advantage of mobile-friendly, web-based technology, in order to minimize the risk of such errors.  In so doing, we participate in ushering in an era of more efficient and confident science.

We have all had that experience.. at some point in our research career!

My own obsession with sharing methods derives from an all-too-common frustration during my PhD. I spent almost a year repeating a technique developed by a previous student, upon which an important part of my research was based. Imagine electrochemically immobilizing an enzyme in an electro-active polymer using a process that required precise control of pH and enzyme activity. During this time, I fully appreciated the importance of the accurate and repetitive dispensing of the correct microliter volume of a reagent used for doping that same polymer. I’m sure you get the point.. not easy, especially when the required level of detail had not been fully committed to paper and the individual had moved to another country to pursue a Post-Doc!

Intuitive lab software enabling easy sharing of protocols

The advancement of science critically depends upon the ability of the researcher to execute a specific protocol, in order to test a hypothesis, and other researchers to be able to repeat it and observe the same results. Errors in the execution of an experiment waste valuable time and resources. Worse still, they may go undetected by the peer review process, potentially wasting the time and funding of other research groups, and ultimately damage the reputation of the researcher.

Enter our innovative lab software: ‘OneLab’

In February 2019, Andrew Alliance launched a unique browser-based lab software environment called OneLab.  It enables researchers to design, and share, their own protocols, through a highly intuitive graphical interface that can then be executed step-by-step, from any PC or tablet.

Imagine being able to set up each step of your serial dilution on an iPad, including all the required lab-ware and reagents.   Once set up, you then execute your experiment either automatically on the Andrew+ robot, or semi-automatically on Pipette+, by remotely setting up the required volumes on an electronic pipette, rather than having to input them yourself.  No more fiddling with tiny buttons with gloved hands, or trying to ready small displays while pipetting!

Intuitive lab software that enables the ‘connected’ lab

Of course, pipetting is just one, albeit highly important, step in a life science experiment work flow. There are others (grabbing, heating, shaking, weighing, and so on) which is why Andrew Alliance is working with partners to expand its offering of connected device solutions and intuitive lab software, towards a more ‘connected’ laboratory.

Not only does this free up time for the researcher to focus on higher level tasks but it also provides full traceability. OneLab acquires data detailing the precise execution of each step of an experiment, beneficial for troubleshooting and ensuring a full audit trail for regulated laboratories.

OneLab is the first intuitive lab software to truly facilitate efficient, centralized programming of connected pipettes and rapid sharing of protocols, enabling laboratories to boost productivity and performance!

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Enter the Andrew Alliance Bluetooth electronic pipette, manufactured by electronic pipette market leader Sartorius at its stat-of-the-art pipette production facility in Kajaani, Finland.  Aside from being the lightest such product on the market, this pipette is also ‘connected’ to Andrew Alliance’s browser-based software environment, OneLab. 

The system is collectively referred to as ‘Pipette+’.

Let’s talk about the software and the benefits as far as the user is concerned.

OneLab is cloud-based and freely accessible, though it can also be made available on a private server.  It enables any one of a wide range of pipetting protocols to be readily created assuming that they are not already available without any programming know-how at all.. just drag and drop what you need either from a tablet, laptop or desktop PC.  These protocols can be readily shared with colleagues as well as being made available for training purposes be it for serial dilution, normalization, qPCR or indeed, many other workflow applications.

OneLab can the remotely set-up the pipette.

Just imagine, you no longer need to press the small buttons on the pipette but have all that done for you – you just need to pick it up when ‘illuminated’, dispense/aspirate, and put back on its smart stand which combines storage with charging, and comprises an embedded PC capable of two-way communication between the pipettes (Bluetooth) and OneLab (ethernet/WiFi).. and let’s be honest, it is a slick design that looks greater on the lab bench.

This ‘connectivity’ with OneLab provides several very important advantages.  Firstly, having the pipetting process automated in these pipettes means that the possibility and likelihood of human error is reduced. User to user variability, to a great extent, is taken out of the equation, meaning that data and results become more reproducibly.  Secondly, this ‘connected’ pipette requires much less hand movement and effort to carry out the same liquid handling tasks as a manual pipette. This provides an easier and more effortless user experience for scientists, while maintaining or even increasing accuracy and precision. 

The fact that step-by-step data is being relayed back to OneLab, along with details regarding the last time and place the pipette as calibrated, means that the user also has complete ‘traceability’.  This ensures complete auditability of the pipetting workflow, especially important for regulated laboratories, as well as the ability to troubleshoot pipetting problems and identify cause.  The crisis of reproducibility in research is in no small part related to the lack of repeatability in pipetting, a problem that also negatively impacts the progress of ring trials as well as resulting in enormous waste of public sector research funding, and the advancement of new life saving therapeutics through the drug discovery pipeline.

The pipettes themselves are based on Sartorius renowned Picus design which continues to demonstrate market leading liquid handling performance married to superior ergonomics.  They comprise a full range of single and multichannel versions, dispensing volumes ranging from 0.2 μl to 10 mL, and whose technical specifications are detailed in the table below.  The pipettes are automatically identified by and paired with the smart charging stand.

Each year at the Society of Laboratory Automation and Screening International Conference and Exhibition, the New Product Award is given to up to three companies showcasing new products that are commercially available within 90 days pre- and post-conference. Products are evaluated by a judging panel onsite at the companies’ booths. Winning products are granted use of the New Product Award designation for a year.  Andrew+ won the New Product Award in February 2019.

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For example, in drug discovery, IC50 assays, commonly used to evaluate drug efficacy, and assay development procedures as well as standard-curve generation involve the serial dilution of compounds, proteins, or detection agents.  These processes can be streamlined by utilizing automated liquid handling equipment with serial dilution capabilities, addressing two common workflow challenges: error propagation across the columns or rows of a microtiter plate due to transfer inaccuracies that lead to less accurate and less precise dispensing; and the risk of error in the calculation of serial dilutions themselves.

This is all well and good but any automation solutions on the market have been developed for high throughput liquid handling, are specific to a limited range of applications, and are priced beyond the budget of many research laboratories who cannot justify investment in automation for lower throughput liquid handling despite unquestionable improvements in reproducibility of the liquid handling steps in their workflow.  This is especially the case if the ‘solution’ cannot be readily adapted to different workflows unless the researcher is well versed in Python or C++, as well as being willing to invest the time in reprogramming their lab automation or hire a programmer, and that is assuming that it can even be reprogrammed, i.e. is an ‘open’ vs ‘closed’ lab automation solution.  Moreover, unlike many ‘ideal’ lab bench set-ups in trade shows, reality is usually very different, with the modern lab being increasingly ‘rented’, space constrained and it has become more important than ever that an automation solution be readily adaptable to different researcher workflows rather than the other way around, most especially in the earlier stages of research.  Fitting a rectangular ‘box’ into a space under a laminar flow hood is rather like trying to fit a ‘square peg into a round hole’. 

Avez-vous l’impression de maîtriser l’automatisation de votre laboratoire… ou que c’est elle qui vous contrôle… ou est-elle simplement reléguée dans un coin du laboratoire, à ne servir à rien ?

The answer to this question likely explains why many laboratories still rely on manual operations to perform tasks, especially when it comes to liquid handling. Fully automated workflows have been achieved in the field of clinical diagnostics, but the same can’t be said for research, due to the flexibility and continuous workflow changes required.

Andrew Alliance has addressed this need in its recent launch of the award-winning Andrew+ robot that is capable not only of automating liquid handling but the manipulation of labware crucial to sample management inherent to many research workflows.

The robot is managed by its state-of-the art browser-based intuitive lab software called OneLab which allows the researcher to not only retain control of their workflow but readily adapt the pipetting robot to a wide range of other workflows using Andrew Alliance Domino accessories, thus making optimal use of space, resources and funding.  OneLab requires zero programming know-how.  Pick up your tablet or laptop, drag and drop the labware you require, volumes to be aspirated/dispensed, calculate your serial dilution in a way that is both highly visual, easily shared with other researchers, and even fun.. and you are ready to go!

This is just part of the story.. two-way communication with Bluetooth pipettes means that each step in the execution of your protocol is recorded along with the calibration data of the pipette itself.  This ensures full traceability as well as a high degree of quality control, especially important if you want to automate costly and complex liquid handling steps associated with qPCR or NGS.  in a simple qPCR experiment, typical pipetting errors with a standard, routinely calibrated pipette, can result in DNA copy numbers varying by as much as 3%. Imagine the impact of that on the results of an important translation biology experiment, or in a regulated diagnostic laboratory!

The Andrew+ itself is based upon the multi-award winning, highly successful, Andrew Pipetting Robot, launched in 2013 and used in many laboratories around the world.

It offers fully automated pipetting, as well as more complex manipulations, using a wide range of accessories and Andrew Alliance electronic pipettes.  Significantly, compared to its predecessor, it hosts 8 and 12 channel pipettes enabling much larger volumes to be dispensed far more quickly.  This is a significant advantage, for example in qPCR and NGS workflows.  It is a complete ‘redesign’ with the ‘+’ referring to the fact that it is a fully ‘connected’ device, able to communicate with both OneLab, by ethernet or Wi-Fi, from which is receives step by step guidance of each step of a given protocol; and with the electronic pipettes themselves, by Bluetooth.  This communication is two-way, with instructions being passed from OneLab to Andrew+, which ensures the remote programming of the pipettes, and back from the pipettes to OneLab, meaning that each step if being fully recorded.

The electronic pipettes comprise a full range of single and multichannel versions, dispensing volumes ranging from 0.2 μl to 10 mL.  They are manufactured by Sartorius in Kajaani, Finland, and based on its market leading high performance Picus design.  These are branded Andrew Alliance as they have been co-developed with Andrew Alliance so that they can work with OneLab.  The pipettes are automatically paired with OneLab via special adapter on the rack to which they are mounted, and this process does not require any user intervention at all. 

Andrew+ has a highly flexible workspace.  It is modular thanks to the use of Dominos.  A simple experiment requires only 2 Dominos whereas Andrew+ could manage up to 11 Dominos for more complex experiments.  The system has been designed to fit the majority of laboratory hoods.  Andrew+ with 2 full rows of Dominos occupies a depth of ~60cm/24”, which would be viable for even the most challenging of hoods. 

Each year at the Society of Laboratory Automation and Screening International Conference and Exhibition, the New Product Award is given to up to three companies showcasing new products that are commercially available within 90 days pre- and post-conference. Products are evaluated by a judging panel onsite at the companies’ booths. Winning products are granted use of the New Product Award designation for a year.  Andrew+ won the New Product Award in February 2019.

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