poster: high-throughput phenotypic screening workflow for cytotoxicity determination

Full recap of this years SLAS2017!

Thanks to everyone who visited our booth! Here’s our recap of SLAS2017…

Making its premiere at SLAS 2017, dragonfly discovery – set to be a game-changing solution to challenges in assay development and high throughput screening!

>> download the dragonfly discovery brochure here

>> watch the dragonfly discovery video here

If you missed our workshop: Assay development into HTS: redefining reagent dispensing

>> click here to request a copy of the presentation

Presenters:

Melanie Leveridge
Head Screening, Profiling & Mechanistic Biology UK, RD Platform Technology & Science, GSK Medicines Research Centre

Joby Jenkins
Director, Product Strategy, TTP Labtech

Abstract: The complexities of assay development and challenges associated with validating and transferring assays into HTS are well-known bottlenecks in the drug discovery process. Industry experts from GSK and TTP Labtech will discuss how these concerns could be addressed by user-friendly, low volume liquid handling instruments that significantly reduce assay development time and greatly improve assay robustness in screening.  dragonfly discovery gives scientists a common platform whereby they can easily develop complex assays and screen those assays in a robust and cost efficient manner.

We showcased our solutions for sample management, liquid handling and detection instrumentation which are ideally suited for use in:

Target Discovery  – simple answers from complex biology

  • arktic – biological library -80°C automated storage
  • mosquito – low-cost, low-volume NGS library prep
  • acumen Cellista – genome-wide library profiling
  • comPOUND – rapid automated delivery from -20°C storage

Assay development – develop complex assays, faster

  • dragonfly discovery – automated multi-channel assay development and validation for HTS
  • mosquito – low-volume compound addition and dilution
  • acumen Cellista – high-content phenotypic screens
  • mirrorball –no-wash, multi-target immunoassays

High-throughput screening – robust and cost effective screening

  • dragonfly discovery – robust, accurate and reliable HTS dispensing
  • mosquito – simple assay ready plate creation and reformatting
  • acumen Cellista – practical uHTS phenotypic screening
  • mirrorball – multiplexed, no-wash immunoassays
  • comPOUND – rapid automated delivery from -20°C storage

Hit-to-lead – progress with confidence

  • dragonfly discovery –  complex assay setup and screening
  • mosquito – low-volume hit picking and serial dilutions
  • acumen Cellista – multiplexed cell heath, multi-parameter 3D assays
  • mirrorball – multiplexed cell-based hit characterisation
  • comPOUND – compact, high-speed cherry picking -20°C storage

Read our posters that we presented at SLAS2017:

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blog: Introducing our travel grant winner

Travel grant winner: Ana Isabel Matos

Last week we announced the first two winners of our travel grant and posterimage_Ana_Isabel_Matos award and promised that we would share their research aims with you. This week, we’re going to speak with Ana Isabel Matos (travel grant recipient).

I was curious to find out more about her research, here is what Ana had to say:

Please tell us which conference you would like to travel to and where/when it will be held?

I am very interested in the 2017 Cancer Nanotechnology Gordon Research Conference that will be held in Mount Snow, West Dover, VT, between 18-23 June, 2017.

Please tell us about your research:

Per year, colorectal cancer is responsible for 655,000 deaths throughout the world. Almost 70 % of colorectal cancer patients are diagnosed with the metastatic form of the disease, mainly hepatic metastases, and present a very low 5-years survival rate. The heterogeneity of cancer cells has impaired the successful outcome of several therapeutic approaches, including surgery, chemotherapy and radiotherapy, requiring effective combinatorial approaches. Immunotherapeutic approaches have shown very positive outcomes in other disseminated malignant diseases. However, an effective strategy against the heterogeneous population of cancer cells requires a combinatory strategy to modulate different cells and mechanisms involved in tumor growth and dissemination. Since the end of last year, I have been involved in a very interesting and interdisciplinary PhD project that aims to develop a combinatorial multivalent nanoplatform for colorectal cancer immunotherapy and drug delivery. Going into detail, this project is focused on the design of two types of polymeric nanoparticles able to carry different active molecules (e.g. tumor associated antigens and immune modulators) and to target and modulate distinct cell populations, mainly dendritic cells and tumor cells within the tumor microenvironment. This highly innovative nanoplatform will lead to a safe multivalent nanomedicine able to modulate tumor microenvironment at different levels by combining the effect of a cytotoxic drug at cancer site with a balanced and multi-targeted immunotherapy, which overall outcome can constitute a real hope for patients with metastatic colorectal cancer disease. During the last year, I had the opportunity to develop and characterize a promising nanosystem. Accordingly, I have learnt how to apply multiple but complementary techniques to achieve a deep characterization of nanoparticle physicochemical properties, including mean diameter, polydispersity index, surface charge, hydrophobicity and stability. In addition, the characterization of the interaction of these delivery systems with antigen presenting cells, namely dendritic cells, was also one of our major goals. As a result, I could extend my expertise in cell culture, confocal microscopy and flow cytometry.

How does your research apply to the topics of discussion at the above mentioned conference? (min 250 words)

The 2017 Cancer Nanotechnology Gordon Research Conference, as the title suggests, provides an excellent opportunity for scientists and PhD students that are working in the field of innovative cancer research

What do you hope to learn/gain from attending this conference? (min 250 words)

The Gordon Research Conference provides a great chance for graduate students, post-docs, and early-career scientists with different levels of knowledge and expertise to get involved in a highly-stimulating and gratifying scientific environment. Particularly for PhD students, this huge conference is a unique opportunity to increase the scientific background in cancer nanotechnology through the deep sharing of recent scientific researches during the expected breakthrough talks. This conference also enables PhD students to present and discuss their current and unpublished scientific research with worldwide team leaders of cancer nanotechnology scientific community. This previously referred aspect is perhaps the most important for a PhD student because it certainly will have a direct effect on the progression of the research project by engaging in scientific discussions and exchanging personal opinions with leading scientists. Looking forward to the future, the Gordon Research Conference can be the precursor of informal networks that can lead to a lifetime scientific collaborations and attainments, by meeting face-to-face scientific leaders from all around the world. Moreover, these informal networks with team leaders and their students can probably create the opportunity for the PhD students to travel to another scientific laboratory anywhere in the world and gain experience in a particular area or technique developed and explored in that laboratory. For all these reasons previously mentioned and taking into account my desire to continue to learn and get more experience in cancer nanotechnology area, I view with great self-motivation and enthusiasm the possibility to attend the 2017 Cancer Nanotechnology Gordon Research Conference by integrating this travel grant.

Don’t miss our blog next week, where we’ll find out more from Carlos Perez Arques (winner of the poster award) about his research aims. Until then, have a great week!

press release: New partnership for out-of-the-box data analysis for high throughput screening

TTP Labtech partners with Genedata to provide out-of-the-box data analysis for high throughput screening

  • The partnership will integrate Genedata Screener® software with TTP Labtech’s acumen Cellista and mirrorball to improve screening data management
  • The Genedata Ready-to-Run integration will be showcased at booths #1105 and #541 at SLAS 2017, Washington, DC, USA, February 4th-8th 2017

Cambridge, UK, 6th February 2017: TTP Labtech Ltd, a global leader in the design and development of automated instrumentation and consumables for life science applications, has announced that it is partnering with Genedata to provide customers with improved solutions for importing and analysing raw data from their screening instruments.

The partnership will integrate Genedata Screener software with TTP Labtech’s high throughput compound and biologics screening tools, including acumen Cellista and mirrorball®. This will provide customers with out-of-the-box fast and efficient connection between their laboratory tools and the Genedata Screener platform, which will enable improved data sharing and visibility across multiple sites. It will also help improve integration and analysis of screening data from multiple sources.

image_acumen_Genedata_mirrorball

 

Genedata Screener software integrated with TTP Labtech’s acumen Cellista and mirrorball

Sarah Payne, product manager, TTP Labtech, commented: “The integration with Genedata Screener streamlines the screening workflow for customers and enables them to analyse and view the results of large screening data sets within one software – all of which drives more rapid and informed decision-making.”

Dr Stephan Heyse, business unit head of Genedata Screener, said, “Genedata partners with leading technology providers to improve operational efficiencies in the drug discovery process. Our Ready-to-Run program provides out-of-the-box integration of the Genedata Screener platform with complex screening instruments, such as those used for cytometry and cellular imaging. This enables researchers to directly benefit from Genedata Screener data harmonization and analysis capabilities for the most complex screening data in a transparent and comparable fashion. We are delighted to partner with TTP Labtech on this integration project.”

blog: Get bitten by the bug at AGBT this year

Get bitten by the bug at AGBT this year

The AGBT conference is the place to be this month for both showcasing and discovering the latest research and technologies making a splash in genomics right now.

With TTP Labtech’s foot now firmly in the door of genomics with our mosquito® and dragonfly® liquid handlers and arktic sample management platform, this is an exciting event for us this year.

We will have many examples of how the mosquito and dragonfly ranges are accelerating genomics research at our home for the conference, room 322, floor 3. Activities will include new poster presentations, application notes, information about technology partners and live demos.

Just for fun.…mosquito lucky dip promotion!

Watch mosquito in action and have a flutter yourself! Any visitor to TTP Labtech can pick 3 microtiter plate wells into which mosquito will dispense coloured liquids from a sealed plate. Match two or three of the colours and you win a prize! All attempts will be entered into a final prize draw for a MAVIC PRO drone camera and 15% off your first mosquito. Join the mosquito club!

Please don’t be shy!

We want to meet as many of you as possible and will be working to take over room 322, floor 3, TTP Labtech’s base for the conference, with a relaxed, open house atmosphere. Speak to our experienced team, including applications scientists who have spent the last few years supporting integration of the mosquitos into genomics laboratories.

Finally, you are invited to join the TTP Labtech team for a night of drinks, fine food and good cheer at the conference dinner party on Monday, 14th February 5 – 7:30 pm, room #322 floor 3.

 

Read on for more information on new material we are presenting at AGBT this year:

Poster presentation by Dr Peter Ellis at The Wellcome Trust Sanger Institute (Cambridge, UK):

‘Accurate quantitation and normalisation of genomic DNA for high-throughput DNA library construction’

The Wellcome Trust Sanger Institute receives up to 20,000 DNA samples each month, the majority of which are destined to be processed through its high-throughput sequencing pipelines.  In order to allow the slick passage of samples through these workflows, it is vitally important that the samples are accurately quantified and robustly normalised to target concentration and volume, especially working with highly variable starting material. Dr Ellis describes an accurate, scalable, inexpensive workflow centred around automated pipetting of DNA and reagents using the mosquito in conjunction with fluorescent DNA analysis; resulting in precise, high-throughput quantitation and normalisation.

Poster presentation by Dr Melanie Adams, TTP Labtech, 1:00 pm – 2:30 pm, Tuesday 14th Feb:

Miniaturization and automation of CEL-Seq2 and SMARTer-Seq using the mosquito HTS liquid handler’

Learn how to miniaturise genomics workflows such as NGS library prep and single cell genomics using validated protocol with SMART-seq and CEL-seq cDNA synthesis, and Nextera XT library prep. We’re presenting two very different two single-cell RNA sequencing (scRNA-seq) protocols currently in use at the Max Planck Institute and the Massachusetts Institute of Technology (MIT). The setup allows for high-throughput parallel processing of single cells on 384-well plates with a significant reduction in reaction volume and hands on time, while maintaining or improving excellent data quality compared with manual liquid handling steps.

The Max Planck Institute workflow was recently published in Cell as part of a study into polypoid macrophage fate in granulomas (http://dx.doi.org/10.1016/j.cell.2016.09.054). The MIT are using their new workflow to power through the many scRNA-seq projects run at the BioMicro Center, MIT’s busy integrated core genomics facility.

Hot off the press

Our brand new application note mosquito liquid handlers for high-quality, miniaturised single-cell RNA-seq workflows: A case study from Stanford University School of Medicine’ will be available AGBT. The case study describes a high-throughput, miniaturised workflow using the mosquito X1 and  HTS to study pluripotent cell differentiation during mesoderm development using single-cell RNA-Seq (scRNA-Seq) recently published in Cell (http://dx.doi.org/10.1016/j.cell.2016.06.011). The publication maps the stepwise gene expression of human embryogenesis, boosting our understanding of human development and opening up new possibilities for regenerative medicine

 TTP Labtech partnership with Advanced Analytical

With this and other examples of the synergy between TTP Labtech’s mosquito and Advanced Analytical’s Fragment Analyser being highlighted, AGBT is the perfect place to discover more about our growing partnership with Advanced Analytics. Talk to our experts and learn more about what’s possible when combining mosquito miniaturisation and automation with Fragment Analyzer high-accuracy quantitation and scalability.

What next?

As well as highlighting the workflows we know that the mosquito and dragonfly can improve, we will also be asking ‘what next?’ for our tireless workhorse technology.

Because we are always looking to find new applications and opportunities to put our technology to work in your laboratories, we invite you to come and find us to see just how easy it is to miniaturise and automate existing genomics workflows to save you time, reagents and money.

Can’t make the show? Don’t miss out! Follow us on Twitter for feeds from the show #agbt17.

blog: When you couldn’t possibly choose the best one!

Travel Grant and Poster Award Winners!

At TTP Labtech, we are committed to aiding in the advancement of scientific discovery. As such, we recently launched two award programs. The first being a £500 travel grant, and the second, a £250 poster award. What an amazing response we had!

We received some really fantastic abstracts from researchers all over the world. Reading through them, I was really impressed with the level of detail some of the applicants went into. There really is a lot of great work happening. Luckily, picking the winner was done by random selection and I didn’t actually have to pick the best one. I don’t think I could have chosen with so many wonderful submissions!

So what were the most commonly mentioned research terms in these submissions?

Here’s a Wordle to help us analyse the response data, as you can see, cells are certainly a hot topic, with cancer studies coming in a close second!

wordleSo who are our lucky winners this time?

We are absolutely thrilled to announce our first two winners and share their submissions with you. Congratulations to Ana Isabel Matos, winner of the travel award, and Carlos Perez Arques, winner of the poster award!

Join us next week when we’ll share their research aims with you!

 

blog: addressing drug discovery bottlenecks

drug discovery bottlenecks – could these be a thing of the past?

Low-volume pipetting has become standard practice for many high-throughput screening (HTS) techniques but there are often issues with the accuracy, reliability and repeatability of bulk dispensing of reagents and samples into high density plate formats used in HTS.

In fact, a bulk reagent dispenser survey calculated that about 10% of all bulk dispensing time/work was disrupted due to instrument failure or dispensing problems [1]. Of these, tip clogging, high dead volume and soaring maintenance costs were rated the most problematic aspects of such dispensers.

Another common bottleneck is in the transition of assays from development in to HTS, with a common complaint being that different plate density and liquid handling techniques have to be used for the two processes.  This is due to the complex combination of variables that need to be assessed as part of the assay development process, and the limitation of automated liquid handling to carry out such tasks; combined with the need for high density (typically 1,536) well plate formats and a reliance on automation for the HTS process.  This miss-match results in a lot of time and effort being invested in ‘converting’ assays from one process to the other/ to ensure they run reliably in HTS. What if the same technology that provides highly accurate and precise low-volume liquid handling in assay development were to be used in high speed bulk dispensing in HTS?

Well, your dreams have come true! TTP Labtech have recently announced their new dragonfly® discovery liquid handler.  The new platform enables rapid and reliable low volume (200 nL upwards), non-contact dispensing from a positive displacement disposable pipette with 96, 384 & 1,536 well compatibility, to allow assays to be developed directly in high density plate formats. The same platform can also perform assay validation and subsequent HTS, which simplifies and aids in a smooth transition in to a high throughput environment.

dragonfly discovery has 10 channels which can be used independently with any liquid type, irrespective of viscosity. The unique combination of positive displacement, disposable tips and non-contact dispensing ensure dead volumes are minimised, and that issues of  tip clogging and cross-contamination are removed, all of which improve the efficiency and robustness of the screening process.

In addition, new software capabilities and DoE interface support the design, development and ability to run complex assays on a standalone instrumnet; thus enabling a simple, swift, user friendly set-up prior to a run.

In summary, it is now possible to use the same technology at all stages of the drug discovery process, easing assay transition, improving assay robustness, whilst remaining cost effective.

The smooth running of drug discovery processes will be featured at the following events:

At SLAS 2017, Washington, DC, USA (Feb 4-8th) TTP Labtech will be presenting a poster describing a high-throughput phenotypic screening workflow for cytoxicity determination using its comPOUND store to rapidly cherry pick individual compounds, dragonfly® discovery for rapid reagent dispensing into 1,536 well plates, and acumen Cellista for reporting medium content data from multiplexed phenotypic screening assays. In this process, dragonfly discovery rapidly dispenses many liquid types (including cells and beads) into a 1,536 well plate with no cross contamination, and minimal intervention.

[1]Comley, J. Bulk Reagent Dispensers: ubiquitous liquid handling tool for microplate filling. DDW Fall 2010

TTP Labtech will be presenting live demos of dragonfly® discovery at booth #1105 at SLAS 2017 along with presenting at ‘Late Night with LRIG – Rapid-Fire Innovation Session’, 6-8pm, Monday 6th February, and will be hosting a workshop on Tuesday 7th February, room: 143b at 2pm. Space is limited, so reserve your place at the workshop here.

press release: TTP Labtech introduces dragonfly discovery

New liquid handling platform to reduce assay development time and improve assay robustness in high throughput screening… meet dragonfly® discovery!

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TTP Labtech Ltd, a global leader in the design and development of automated instrumentation and consumables for life science applications, has announced the commercial premiere of its dragonfly discovery liquid handling technology at SLAS2017, in Washington, DC, USA.

Building on the success of the first dragonfly liquid handling platform, dragonfly crystal, which was designed for crystallographers, TTP Labtech has developed a second generation of the dragonfly technology. The new dragonfly discovery is poised to address the complexities of assay development, and challenges associated with validating and subsequent transferring of those assays into high throughput screening (HTS), which are well known bottle necks in the drug discovery process. This novel, user-friendly, low-volume liquid handling technology significantly reduces assay development time and greatly improves assay robustness in screening. The dragonfly discovery provides scientists with a standard platform whereby they can easily develop complex assays and screen those assays in a robust and cost efficient manner.

The new platform enables rapid and reliable low volume (200 nL upwards) dispensing from a positive displacement disposable pipette (with 4 mL capacity), and 96-, 384- & 1536-well compatibility, to allow assays to be developed directly in high density plate format using a common liquid handling platform. The same platform can also perform assay validation and subsequent HTS, which simplifies the process of assay development and aids a smooth transition in to a high throughput environment. In addition, a new software capability and user interface support the design and development of complex assays.

Joby Jenkins, director – product strategy, TTP Labtech, commented: “In the development of dragonfly discovery, our aim was to redefine reagent dispensing. Positive displacement pipetting is well known to be agnostic of liquid class and offer exceptional reliability, but it has never before been used for non-contact bulk reagent dispensing. This, combined with the fact the tips are disposable, results in an extremely accurate and reliable dispense technology, which is something the industry has been crying out for.”

TTP Labtech will be presenting live demos of dragonfly discovery at booth #1105 at SLAS2017, Washington, DC, USA, 4 Feb – 8 Feb 2017. The company will also be presenting during the ‘Late Night with LRIG – Rapid-Fire Innovation Session’ at the conference, 18:00 – 20:00, Monday, 6 Feb 2017, and will be hosting a workshop on Tuesday, 7 Feb 2017,  room: 143b at 2pm. To reserve your space for the workshop visit here.

blog: New drugs need bold approaches

Turning the screening scenario on its head

The pharmaceutical industry is under immense pressure to find better ways to bring new drugs to market, given the dwindling pipeline and the astronomical cost of late-stage failures. So, is the screening pool from which we select compounds just too small, or not chemically diverse enough?

Screening library subsets is designed to capture all the areas of the chemical space within a company’s full compound library, but by screening a much smaller number of compounds to allow the use of more complex phenotypic assays that provide data closer to the in vivo goal.

“However,” says TTP Labtech’s Dr Paul Wylie, “I believe that this approach is flawed as the subsets are selected on target-based information. Using data from historic target-based screens to select subsets for phenotypic screens runs the risk of missing good quality hits – or selecting poor compounds for next stage interrogation. Just because a compound is in a similar chemical space to another molecule, doesn’t necessarily mean that it will exert the same phenotypic response, in vivo.”

A good example is the catecholamines: dopamine, noradrenalin and adrenaline.  Whilst they only differ by the addition of a single functional group, they exert very different physiological responses (see table 3).

structure function
dopamine  mirrorball_blog_dopamine_Dec16 Inside the brain, dopamine plays important roles in motor control, motivation, cognitive control, reinforcement, and reward, as well as a number of basic lower-level functions including lactation, and nausea.
noradrenaline  mirrorball_blog_noradrenaline_Dec16 Medically it is used in those with severe hypotension. It does this by increasing vascular tone (tension of vascular smooth muscle) through α-adrenergic receptor activation.
adrenaline  mirrorball_blog_adrenaline_Dec16 As a medication it is used for a number of conditions including: anaphylaxis, cardiac arrest, and superficial bleeding. Maybe used for asthma when other treatments are not effective. Inhaled epinephrine maybe be used to improve the symptoms of croup.

Table 3.

“In my view,” says Dr Wylie, “it is time to turn the screening scenario on its head. Screening is about excluding the compounds that are not useful; so, instead of screening in a target-based way first, then using a phenotypic response to backup the data, we should screen phenotypically and follow up with target-based identification.”

What would be the requirements to successfully implement phenotypic screening at primary throughputs? “Target-based screening was adopted partly because it was easy to automate, fast, reproducible and relatively inexpensive to run on very large compound sets”, he explains. So, just how far off running a full deck phenotypic screen are we?

We would need:

  1. Automation to run assays in 1536-well plates, to achieve the required throughput. Many liquid handling systems are now able to do this very effectively.
  2. Manageable cell costs/cell numbers. Primary cells and iPS cell lines are more physiologically relevant but incur higher costs. HTS requires the use of around 100 cells per 1536-well plate to make these cost-effective.
  3. Consistent, fast scan and analysis times to fit into a fully automated HTS process. This is important because many HCA instruments have variable read times.
  4. Manageable data files from 2-3 million wells.
  5. Straightforward biology.

Dr Wylie believes that throughput and assay complexity are perceived to be the main barriers to running a full deck phenotypic HTS, but, he asks, “Is that really true?”

  • The biology itself can be limiting, but only in certain projects. Phenotypic screening is robust. “Many phenotypic assays look at quite basic readouts: cell viability (live dead/apoptosis), reporter gene expression, cell cycle, angiogenesis formation. These are simple assays to screen,” he points out.
  • For throughput: “it is true that many typical imaging systems do not fulfill the criteria for a HTS manager to run in a full-deck screen. So it is best not to use a standard microscope-based imaging system”, he concludes.

Laser-scanning imaging cytometers (LSICs), such as acumen Cellista (TTP Labtech), combine object recognition with bulk read speeds (typically under 5 minutes per 1536-well plate). It requires fewer cells (typically 100/well). It also produces very small file sizes, so the IT requirements are the same as for target-based screening. These features mean that LSICs like acumen Cellista are ideally placed to remove the compromises and offer practical high throughput, full deck phenotypic screening.

“The costs of phenotypic primary screens are higher than traditional target-based screening; but it is surely much cheaper than pursuing poor compounds which fail at later stage drug development,” explains Dr Wylie.

“I believe the only barrier to running full deck phenotypic screening today is the willingness and belief to accept it as a key area of drug screening and then to implement it.”

news: Affordable automation for protein crystallographers – the ultimate lab bundle for 2017

Affordable automation for protein crystallographers – the ultimate lab bundle for 2017

Starting in 2017, our lab bundle pack is designed to automate your crystallisation drop setting and optimisation whilst meeting increasingly demanding budgets. With over 300 academic publications in 2 years referencing mosquito, we know how important it is to provide you with productivity and peace of mind in your daily research. Utilising the superior positive displacement technology of TTP Labtech’s mosquito and dragonfly, you can benefit from unrivalled accuracy and repeatability of across a wide range of viscosities, combined with effortless, intuitive software accessible to even the most novice user.

  • 3 protein crystallisation instruments
  • 2 year full warranty
  • 1 unlimited software licences

>>Get your lab bundle

The lab bundle pack includes:

  • mosquito® crystal (2-way) & dragonfly crystal® (5-head) & MXone
  • consumables pack for mosquito & dragonfly
  • extended 2-year guarantee including a product maintenance visit
  • unlimited software licences

TTP Labtech’s mosquito & dragonfly delivers:

  • unrivalled accuracy and repeatability at nanolitre volume using our unique true-positive displacement technology
  • versatile workflows to miniaturise and automate processes to save time and precious crystals
  • robust and very easy to use, suitable multi-user labs
  • proven track record of research success by 300+ publications in 2 years

>>Get your lab bundle

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