How does a piece of DNA become a person? What happens at the DNA level if somebody becomes ill? To be able to answer such questions, start-up LUMICKS developed the first microscope in the world that can show in real-time how DNA and proteins respond to each other at the molecular level. NanoNextNL programme director Gijs Wuite from the programme 8B was one of the founding fathers of this microscope.
photo: state secretary Sander Dekker and Andrea Candelli (Lumicks) – credits: VU Amsterdam
Cancer, diabetes, muscular diseases or cystic fibrosis: errors in the DNA form the underlying cause of a range of diseases. To be able to understand what goes wrong and when it would be fantastic if you could observe the processes in which DNA and proteins interact with each other at the molecular level. That is exactly what can be done now thanks to a combination of techniques that start-up LUMICKS has incorporated into a microscope named C-TRAP.
A second product even makes it possible to manipulate and measure thousands of molecules at once. Thanks to that this Acoustic Force Microscopy technique is suitable for point-of-care diagnostics, such as measuring glucose levels with a finger prick, says Olivier Heyning, CEO of LUMICKS. ‘Now in some cases it takes two weeks for a specialised lab to analyse blood samples. Our technology can be integrated into a handy device that can recognise certain viruses within a few seconds, for example, without the need for any cells to be cultured.’
From static to dynamic
‘Up until now scientists have mainly worked with tools that can study static situations’, says Heyning about the development of the C-TRAP. ‘From a biological point of view it is very valuable to be able to follow exactly what happens during the interaction between molecules.’ The research group of Gijs Wuite and Erwin Peterman from VU University has worked for more than ten years on techniques such as optical tweezers – with which focused beams of laser rays are used to hold an object – fluorescence microscopy and systems to manipulate fluid at the microscale. Via LUMICKS, a combination of these techniques has now become available as the product C-TRAP, which can be used by other researchers and the pharmaceutical industry.
Thousands at once
‘With our combination of optical tweezers, fluorescence microscopy and microfluidics we saw for the first time exactly what happens with DNA when it is organised by proteins, a process which you previously needed extensive modelling work for’, says Heyning. Fantastic of course but still not good enough. Scientists must be able to make thousands of measurements of identical molecules for their results to be statistically significant. ‘Therefore the group of Wuite and Peterman has developed a new way of being able to manipulate and measure thousands of molecules at once.’
By pushing away the red beads with ultrasound, the force needed to stretch the molecules can be measured.
Manipulating with sound
The so-called Acoustic Force Microscopy (AFS) method works using ultrasound. Each molecule to be investigated is affixed on one side to a glass plate and on the other side to a small plastic ball. With the help of ultrasound researchers can push away the balls in a controlled manner and note the force required to stretch or break the molecule. This gives an insight into the structure and functioning of the molecules.
‘We are now busy testing different prototypes together with clients. Up until now they are all very enthusiastic’, says Heyning. The company also has a healthy financial outlook for the time being. The start-up recently received a Take-off grant from Technology Foundation STW, a Horizon 2020 Future Emerging Technologies (FET) Open Grant from the EU and financial support from the NanoNextNL Valorisation Programme to bring the AFS technique to the market. In addition, the first systems have already been installed at a university in Göttingen and at the Harvard Medical School.