Impact case study database

Atomic force microscopes have been commercially available since the early 1990s. Since then, several companies have built and sold AFM instruments, including Bruker (US), Agilent (US), JEOL (Japan), Park Systems (South Korea), Oxford Instruments (UK), Nanosurf (Switzerland), Hitachi (Japan), Horiba (Japan), WITec (Germany), NT-MDT (Russia), NanoMagnetics Instruments (UK) and Nanonics Imaging (Israel). Such instruments are now routinely used for surface analysis in academic and industrial research. In 2019, the AFM market was worth USD441,000,000 and is projected to reach USD586,000,000 by 2024 ( S1). By various acquisitions and further developing AFM, Bruker has become the market leader in this field. Its Bruker Nano arm of the business, which Professor Hoogenboom has been collaborating with for AFM, accounted for approximately 30% (USD632,700,000) of the company’s USD2,100,000,000 revenue in 2019 ( S2).

Key parts of the commercial success of Bruker’s AFM instrumentation have been the continuous technology development towards achieving high-resolution imaging with decreasing amounts of user input, and of AFM probes that are of more consistently high quality. These developments have been inspired and supported by research at UCL and led to improvements in instrumentation; protocols for benchmarking the quality of AFM instruments as demonstrated by double helix DNA imaging; and guiding the development of a new AFM probe.

Contributions to improving Bruker’s AFM instrumentation

The relationship between UCL and Bruker emerged in 2012 stemming from AFM instrument development in Professor Hoogenboom’s lab ( R1). This led to the establishment of a joint development agreement between UCL and Bruker, with the overall aim to improve Bruker instrumentation to realise the high resolution achieved in published work from UCL which demonstrated DNA double-helix imaging. The collaboration with Bruker involved improving a beta-version of a Bruker AFM microscope. The instrument was modified to reduce the noise in the optical detection of the AFM probe and it included a new proprietary method of cantilever actuation and imaging mode, named “PeakForce Tapping”.

Guided by investigations at UCL and at its headquarters by UCL researchers, Bruker used data from these experiments to improve its equipment, as well as the robust and reproducible characterisation of DNA at double helix resolution on Bruker instruments as detailed in their published paper ( R2). The resulting methods have continued to be used at Bruker as a standard protocol to optimise imaging parameters.

Developing benchmarking methods to demonstrate high quality instrumentation and improving promotional material

To guide and demonstrate the success of improvements to instrumentation and/or methods, well-defined benchmarks are needed. An ideal benchmark is representative of a large class of AFM samples (actual and potential) that are inexpensive, widely available, easy to prepare for AFM; and sets a high bar for instrument performance. The Hoogenboom group’s research on imaging DNA and resolving the major and minor grooves of the double helix has become the benchmark in the Bio AFM market; as the criterion of double-helix resolution puts high demands on the way in which AFM probes are actuated and detected and on the quality of the probe. The high-quality DNA double-helix imaging provided an accessible and easily recognisable benchmark for Bruker’s PeakForce Tapping mode against its competitors and strengthened Bruker’s position with respect to competitors. The Director of AFM Product Management and Applications Development at Bruker Nano Surfaces stated: “As a result of the improved sample preparation protocol and the quality DNA double helix images Dr Pyne had captured, we were then able to use these images, benchmark PeakForce Tapping Mode against peer methods and provide proof of performance in some of our tender responses” ( S3).

Furthermore, Bruker used the research and protocols pioneered by the Hoogenboom group as input for an application note 142: Imaging of the DNA Double Helix with PeakForce Tapping Mode Atomic Force Microscopy ( S4) and promotional material as exemplified by the cover illustration of the 2013 edition of the journal Microscopy & Analysis ( S5). The application note and promotional materials have been included in presentations by Bruker’s representatives, as they served to demonstrate the performance of Bruker instrumentation to existing and prospective customers; therefore widening the use and customer base of the company.

Improving training and development for company employees and customers

In the wake of UCL’s publication on DNA imaging ( R1), Dr Pyne from UCL travelled to Bruker Nano’s R&D Headquarters in Santa Barbara, California in 2015 where she delivered hands-on training, based on the methods for high-resolution DNA imaging developed at UCL to ten of their approximately 40 Application Scientists representing each of Bruker’s sales regions (NA, EU, APAC, Japan). A Senior Sales Engineer at Bruker UK confirmed learning from the workshop has continued to be used “These Applications Scientists have all used this training as part of their customer systems demonstrations and several have provided the same training to other Apps Scientists in their respective regions.” ( S3)

Dr Pyne also provided a written manual to Bruker’s application scientists, enabling them to demonstrate Bruker instrument performance to customers worldwide. Bruker’s Director of Product Management and Applications Development commented: “The manual on the scanning parameters for single molecule DNA, co-authored by [UCL scientist] Dr. Alice Pyne and Dr. Andrea Slade (Bruker), has allowed this invaluable knowledge to be passed on within the company (including to Bruker staff in EMEA, USA, Japan and Asia Pacific regions) and to customers alike” ( S3). This manual has provided “reference material to assist them [customers] in high-resolution imaging studies of their own samples”, which has facilitated the delivery of Bruker’s “larger goal […of] enabling our customers to do more new and exciting research” ( S3).

Impact on development and sales of AFM probes

In addition to AFM instrumentation, Bruker also develops and sells AFM probes to use with its own and other AFM systems. Complemented by experiments carried out by UCL scientists in London and Santa Barbara, the UCL research on DNA imaging facilitated Bruker’s development, testing, and benchmarking of new lines of AFM probes ( R1, 2). The impact of the Hoogenboom group’s work on directing probe development is corroborated by testimony from Bruker, “the knowledge gain from the collaboration with Dr Pyne and Professor Hoogenboom has led to focused investment” and that “During our collaboration, Alice [Pyne] was a member of the Bruker Team who, together with Bruker Probes Engineers, Dev Apps Scientists, and Sales Apps Scientists, worked on the development of specialized high-resolution imaging AFM probes” ( S3). The most tangible result of this has been the development of what is now Bruker’s PeakForce-HIRS-F-A/B product line ( S6). These probes were first launched in 2015 as a direct result of Dr. Pyne’s benchmarking and prototype evaluation work on DNA and generated a new source of revenue for the company. The probes were the first to specifically enable high-resolution imaging on single biomolecules as they were designed for robust double helix imaging. Due to the high technical specification of these probes, they are sold in multiples of 10 at more than GBP50 per probe. This is more than double that of other probe models available from Bruker. The PEAKFORCE-HIRS-F-B probes are advertised as “ The world's first probe targeted at delivering high resolution on single biomolecules” and are recommended for “…highest resolution fluid imaging of individual, isolated bio-sample such as resolving the DNA double helix - the BioAFM market's standard for demonstrating highest resolution performance” ( S6). A Senior Sales Engineer at Bruker UK said: “Our [Bruker’s] customers have confirmed that these probes are indeed very useful for AFM studies in molecular biology and we continue to offer them as part of our high-end probe catalogue” ( S3). In 2017 the Bruker Nano Group reported a USD58,400,000 increase in revenue on the previous year. Much of this increase has been “driven by solid performance in academic and industrial materials research markets for our X-Ray, nano surfaces and nano analysis tools” ( S2). This increase also corresponds to the introduction of PeakForce Hi-Res F-A/B series demonstrating that sales from the line have contributed to the increase in Bruker’s revenue.