Automation may seem a straightforward task, for those who have not tackled it before
As an attendee of Advances in Genome Biology and Technology (#AGBT19) there are plenty of new things to check out, and while it may not be as cutting edge as spatial genomics or mRNA isoform discovery from long single-molecule reads, liquid handling automation is an important component. And in the next-generation sequencing market, simplifying the workflow through automation yields straightforward benefits of saving expensive and valuable technician labor, increasing reproducibility, and increasing overall laboratory productivity.
Looking back at the Gen Cell Biosystems’ CLiC and Illumina’s NeoPrep
Writing these blog posts over the years serves something like an extended, albeit public, notebook of interesting things that have caught my attention. I had to search my own website (now that’s meta for you) for this post about the Irish company Gen Cell Biosystems platform called the CLiC. This technology was interesting – 384-well format, and the unique dual-layer of oils with a small droplet for on-deck PCR protocols (such as AmpliSeq from Thermo Fisher Scientific) enable small volume library preparation, for many samples and saving on reagents. Gen Cell Biosystems was acquired by Becton Dickinson and Company in October of 2014, and the market has yet to see any product come out of it.
Reading that same post, I mention Illumina’s NeoPrep system (in 2014 it was only known as Advanced Liquid Logic as an acquisition). The NeoPrep Library Prep system launched in early 2015 at #AGBT15, only to be pulled from the market in early 2017, as friend Keith Robison details here. Another friend James Hadfield has this helpful writeup of the NeoPrep with all its pluses and minuses when it launched, and looking at it now the NeoPrep had a lot of promise. However, it simply failed when in the field, and Illumina pulled the plug on the entire product. Those with longer memories recall the Eco qPCR system, a technology acquired and offered to the market in 2010-2013 and then pulled, however not due to product failure but low market adoption.
I spoke with a high-throughput user who had one of the NeoPrep systems, and they told me it ‘just did not work, and our FAS (Field Application Scientist) was told just to wait for further instructions’. After a few months of trying, they simply returned it. If you’d like to buy a used NeoPrep ‘Condition is as new, manufactured in 2015’ you can do so. I’m not sure though where you would obtain consumables for such an item!
Open platforms have open-ended flexibility at a price
Open platforms (i.e. Hamilton, Tecan, Beckman-Coulter are the leading brands) have a firm presence in the marketplace, and have great flexibility for sample preparation (i.e. DNA or RNA purification), on-deck processes (such as a heat block or thermal cycler), and sample volumes (i.e. accommodating 5 mL blood samples). There are options regarding whether it is only 96-well, or 96-well plus a myriad of options (384 well or even 1536), the configurations are flexible as well as the application.
Which brings up the price of this flexibility: you need to know your way around the specifics of the controlling software; every vendor has their own proprietary software with its own way of handling liquid viscosities (e.g. ‘liquid classes’), and their own way of handling errors. One startup that is trying to open up the protocol and lower the price of liquid handling is a 2014 Kickstarter project called OpenTrons, however looking at their OT-2 system, it has only a single pipette, limiting throughput.
The single-purpose Agilent Magnis NGS Prep
As mentioned above with Gen Cell and the NeoPrep, there is demand for automated targeted enrichment; plenty of vendors offer both single-purpose DNA sample purification (QIAGEN, Promega and Roche come to mine) with their own consumables. However to-date there isn’t any vendor of enrichment technologies with a single-purpose automation solution.
Agilent’s Magnis NGS Prep has automated the SureSelect XT HS target-capture, taking purified DNA and producing libraries in a completely hands-off workflow. If I remember the conversation I had with the kind folks in the Agilent suite, it takes about 11 hours from DNA loading to quantification-ready library. There are several nice aspects built-into this unit: touchscreen controls, barcoded strip-tube reagents to confirm that the proper reagents are in the proper locations, and even a green light that bathes the interior when the unit is running, and a red one when an error mode is tripped.
In addition according to the Agilent Magnis NGS Prep brochure (the Agilent webpage is here, and the PDF brochure is here) loading the instrument takes only 5 minutes, the instrument ‘self detects and tunes’ (hmm, I have no idea of what a ‘self detecting’ instrument is actually doing, and I think the word choice of ‘tunes’ should be ‘calibrates’ as this is not a musical instrument, but I digress). Being auto-calibrating is important – if the consumable tips are not properly registered with the deck there will be a major crash; having something called fiducials which can properly align the tip-head with the instrument deck is important, and not having to do this alignment manually is a major benefit to the end-user and a nice technical accomplishment.
Agilent’s press release indicates input as low as 10 ng and has ‘optimized performance for poor-quality specimens’, which means FFPE (Formalin-fixed, paraffin-embedded) samples.
Available June 2019
You should not be surprised that Agilent does liquid handling, as their Bravo systems may not be as popular as the others mentioned above but do have a reputation for robustness. The Magnis NGS Prep system is worth a look for any of you that run an NGS laboratory with SureSelect enrichment chemistry. Also if you are in the market for automating your library preparation, Illumina has put together a useful resource called the Buyer’s Guide to Laboratory Automation. (PDF)