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Thomas's sound methods

Thomas’s sound methods can pick out cancer cells

Thomas Laurell in his lab.

Thomas Laurell was born into a family of doctors. So perhaps it is not so strange that as a professor of engineering he has spent so much time researching biomedical engineering.
“My mother and father and all my siblings except one are doctors! I grew up with medical discussions around the dining table”, he explains. “That is another reason why I applied to Measurement Technology, following in the footsteps of Hellmuth Hertz and Kjell Lindström”.

 

Once there, he mainly developed microchemical methods for detecting diseases in blood samples, for example. In 2000 the Hertz laboratory was inaugurated, a cleanroom lab in which such tests are carried out using silicon chips.

Thomas Laurell is studying methods that are comparable to finding a needle in a haystack, except thahe’s looking not for needles but rather for cancer cells in the body.

About a decade ago, Thomas and his colleagues found a new area of application for ultrasound technology. Just as within a colour printer, the energy in the sound could be used to deflect a beam or to move particles that flow in a stream inside these chips. This approach made it possible to pick out the fat in the bloodstream, which could save heart patients from suffering blood clots during surgery.

The method has generated exciting developments and has led to many international contacts, in particular with Asia. Since 2009, Thomas Laurell has been a “distinguished professor” in Korea (Dongguk University in Seoul) and he also cooperates with Japanese colleagues, as well as recently starting a collaboration with a group in Singapore.

About acoustophoresis (see fact box) he says:

“It’s like on a motorway, you can help the cars (the cells in the liquid) to change lanes by exposing them to the correct intensity and frequency of sound. Tumour cells move over to the fast lane and are removed from the traffic further on. You can collect cells by leading them into a lane of their own, thus concentrating the content in a solution step by step by running it through several times. The process replaces centrifugation in the medical lab.”

“The aim is to discover cancer and other diseases with greater speed and certainty. The mysteries of cancer are many. All tumour cells are not malignant, either”, he says.

Thomas is often out meeting doctors and others who work with medical methodology.

”I meet them to look for new issues. What do the physicians need help with? It is also a way of getting new contacts, cooperation partners and projects. Then I can start to consider and test solutions here at the department in order to get going.”
Research in the field has grown from two half-time doctoral students to 10-12 people in a little more than 5 years. The development has been facilitated by support from Vinnova and the CellCare programme, and just as that support was about to come to an end, news came in the autumn about a new five-year funding plan worth SEK 33 million from the Knut and Alice Wallenberg Foundation. The money is to be shared between Thomas Laurell, Dr David Ulmert and Professors of Medicine David Erlinge and Hans Lilja, Clinical Chemistry, at Lund University as well as Henrik Bruus, professor of Physics at the Technical University of Denmark.

The cooperation with Seoul has been ongoing since 2009. In June, two post-docs will come from there to Lund to work on diagnostics for two years. Instead of antibodies as disease markers, aptamers are used, as they are easier to produce. They can be copied with the help of enzymes and placed in a “library” of different sequences that can find diseases. Those that bind most tightly remain after washing and after several such cycles, the number of relevant candidate diseases is significantly reduced. Commercial chips are being developed for HIV and meningitis and soon also for pancreatic cancer.


“The experiments look promising. Studies on clinical trials can soon be carried out. The background of several million white blood cells is reduced to between 10 000 and 1 000. Then we believe that the molecular biology methods have a good chance of finding the tumour cells.”

Laurell and Hans Lilja would like to adapt the technology to prostate cancer. Their colleague at the department, Per Augustsson, has developed a method to find circulating tumour cells in the blood, which can lead to metastasis. Among one billion blood cells, perhaps ten tumour cells need to be found. The tumour cells in the blood can be identified through their surface proteins when 7 ml of blood are run through a chip.

Per Augustsson was awarded the Sparbanken Färs & Frosta prize for the best doctoral thesis at KLTH in 2012 and has been given the Swedish Research Council’s post-doc grant to study cell-sorting at MIT in Boston. There he is to combine acoustophoresis with their lab-on-chip technology. The aim is to get quick answers from samples: “sample in – answers out.”

Thomas visits Korea a few times a year to set up strategies, apply for funding and teach on a minor scale. A doctoral student at LTH helps with the cooperation, which has received support from STINT.

In Tokyo, Thomas Laurell collaborates with professor Teruo Fuji on developing cell acoustics. Cells are trapped on a chip to map their genetic content. Maria Nordin helps out with her chip which can concentrate a solution several hundred times.

“Through practical experiments, we learn more and locate the problems. There is evident interest and openness to new cooperation from Asian countries even though American industries are also showing great interest”, says Thomas. Extensive cooperation with BD Biosciences, for example, is a result of the strong environment generated by Vinnova’s investment in CellCare.

Some of the findings are commercialised in the company Acousort AB. Some previous companies, among them Erysave, were not a great business success. “The technology has to be further developed before one goes out as a company”, Thomas has learnt.

Text: MATS NYGREN

Facts/Acoustophoresis

Acoustophoresis is a method for sorting and separating cells using sound waves. Standing sound waves affect the content of a liquid that runs through channels in a silicon or glass chip; the channels are as thick as three hair’s breadths. Depending on the size of the cells and other properties, they can be sorted into different channels for use in research into new treatment methods for a series of different diseases such as Parkinson’s disease, cancer and blood disorders. Thomas Laurell cooperates within the project with the Department of Laboratory Medicine at SUS, the Neuronal Survival Unit at the Faculty of Medicine in Lund, the Stem Cell Centre in Lund, and the Division of Haematology and Transfusion Medicine at SUS.

More scientific information can be found here:
www.elmat.lth.se/forskning/nanobiotechnology_and_labonachip/

Thomas Laurell
Thomas Laurell was born in 1961. He is professor of medical and chemical microsensors at the Department of Measurement Technology and Industrial Electrical Engineering. Since 2007 he has been a member of the Royal Swedish Academy of Engineering Sciences and since 2010 of the Royal Swedish Academy of Sciences. He is part of Create Health which researches cancer treatments. For 20 years, he has been developing methods of bioanalysis based on lab-on-a-chip. He got the 2009 AkzoNobel Science Award for his successful interdisciplinary research. He has been involved in starting four new companies, applied for 28 patents and written 160 research articles. He heads a division for nanobiotechnology and shares the responsibility for Clinical Protein Science at BMC with György Marko Varga.

Facts/Acousort AB
Acousort AB is a company that was set up 1.5 years ago and has been met with interest from the biotech industry for its patented cell-handling technology. It was also recently awarded SEK 0.5 million from Vinnova to develop its first industrial prototype. Its offices are at BMC and it also conducts studies for the cell-handling industry. They are happy to avoid expensive centrifugation and business is now going so well that external capital has not yet been required – a positive cash flow already in the first year! Read more on www.acousort.se.