Research

Our medical target areas include infection biology, neuroscience, and cancer. These areas are, however, likely to expand due to the expected wide applicability of nanotechnology. Nanotechnology-platforms under investigation include nanoparticles, DNA nanotechnology and organic bioelectronics. In addition to this, platforms are brought to the center as collaborations are established with researchers at national and international academic settings.

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Adapting the Microenvironment to Regulate Leukocyte Function

Mia Phillipson

 

The local microenvironment greatly influences on recruitment and function of immune cells, and we investigate means to shift this environment depending on demand to enhance bacterial clearance, angiogenesis or induce immune-privilege. To understand the role of distinct immune cells in blood vessel formation we have developed a model where we can visualize and track immune cells in parallel to ongoing angiogenesis.

MiaP mic bild Involvment of leukocytes in revascularisation and engrafment of transplanted islet

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Different aspects of microfluidics

Helene Andersson Svahn

The Nanobiotechnology group at the Royal Institute of Technology in Stockholm, Sweden, is focusing on interdisciplinary research combining nanotechnology and microfluidics with various biotechnology and medical applications. The research group consists of approximately 18 people with a wide variety of backgrounds such as electrical engineering, medical, biotechnology, chemistry and physics creating a very dynamic and interdisciplinary environment. We are currently focusing on four different areas, droplet microfluidics, microwell plates, paper-based microfluidics and clinical microfluidics.

The droplet microfluidic system was recently developed and is currently the only setup of its kind in Scandinavia. Thus far, we have developed a number of different assays including an assay for detection and analysis of cell surface protein biomarkers on individual human cells using enzymatic amplification inside microscale droplets. The method provides increased sensitivity with high throughput, and permits analysis of several cell samples concurrently by incorporation of droplet optical labels. This work was recognized in Nature Materials as a research highlight. We have also developed a fluorescence based homogeneous assay for protein analysis, passive separation of droplets by size based on cell-induced droplet shrinkage and improvements in robust and inexpensive microfluidic device fabrication for optical analysis. In March 2011 we had the first dissertation on droplet microfluidics in Scandinavia, addressing high throughput biological analysis.

droplet

Figure 1. Each droplet functions as an individual reaction vessel with volumes in the picoliter range.

 

 

We have also developed a microwell chip (672 wells of 500 nl) consisting of glass and silicon, with a spacing between wells that is compatible with automatic sorting of single cells into individual wells. This chip has been applied in many different biological studies, for example single leukemic non-adherent cancer cells were investigated for their heterogeneity in cell proliferation. The chip has subsequently also shown potential in protein analysis, mutation analysis by PCR, microfluidic integration and also for stem cell research. The combination of 1) the hundreds of experiments that can be run simultaneously in the chip and 2) the small volume per well saving reagent cost in molecule screens, makes the microwell chip a perfect match in cell research where high-throughput analysis is of utmost interest and the cellular effects of expensive molecules often are to be studied.

microwell

Fig 2. The microwell slide holding 672 wells optimized for cell based assays.


To overcome limitations for wide application of clinical microarrays, such as high cost of assays need for skilled technicians, need for advanced equipment and long assay times, our lab has developed two novel assay formats that allow for rapid, inexpensive, portable and easy to use microarray analysis. 1) Affinity-labelled superparamagnetic microparticles are actuated by magnetic fields to provide a detection technology which within seconds allows for a naked-eye or cell-phone camera analysis of microarray results with retained assay performance. 2) A paper-based substrate is used to create a lateral flow microarray assay which, together with affinity labeled gold nanoparticles allows for convenient ten-minute high density microarray assays and naked-eye or cell phone camera analysis. We hope that developments made by our group and others will be useful in translating the impressive advancement in lab-based diagnostic methods into integrated low-cost diagnostic devices amenable for field use, point of care, health care points and emergency medicine situations.

The clinical microfluidics team is focusing on applying engineering principles and technologies, especially micro-technology, to clinical medicine. The group expertise is within Bio-MicroElectroMechanical Systems with emphasis on sample preparation. Ongoing projects include the development of point-of-care blood diagnostics for bloodstream infectious diseases, host response to allergy and rare cell isolation for cancer diagnostics. The group is involved with several EU projects and currently coordinating one FP7 project, (highly integrated optical sensor for point-of-care label-free identification of pathogenic bacteria strains and their antibiotic resistance, www.intopsens.eu) and participates in two more projects, rapid point-of-care test platforms for infectious diseases (http://www.rapp-id.eu) and digital sequencing (www.digitalsequencing.eu).

Please visit the following link to see the full publication list of the Nanobiotechnology group, http://www.biotech.kth.se/nano_biotechnology/publications.html

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Nanoparticle development

Andreas Nyström

In order to find new therapeutic and drug delivery systems for cancer treatment, we are working on the development of new nanoparticle systems that can be applied in the treatment of cancer. We focus on using polymeric materials and advanced polymeric architectures for tuning physiochemical properties to our advantage. Current projects include combined siRNA and chemotherapeutic delivery. This work is done in collaboration with Prof Dan Grandér and Assoc. Prof Theoharis Panaretakis at Oncology-Pathology Karolinska Institutet and Assoc. Prof Michael Malkoch at the Royal Institute of Technology.

Funding is provided via a collaboration grant from the Swedish Research Council – Medicine.

References

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Organic bioelectronic devices

Agneta Richter-Dahlfors

We develop an array of organic electronic devices, which translates electronic input signals to the delivery of chemical substances (cations, neurotransmitters). These tools are used to improve the precision in cell biology experiments. An exact number of chemical molecules can be added to cells at very high spatiotemporal precision. We apply these devices to address complex Ca2+ signaling patterns within and between neurons.

Please follow the link below to the preface of our edited special issue on Organic Bioelectronics in Biochimica et Biophysica Acta (BBA) - General Subjects for a summary of the field.

Organic bioelectronics — Novel applications in biomedicine

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Nanoparticles for targeted multimodal diagnostic imaging are designed for SPECT and 19F-MRI utilizing non-ra-dioactive 19F for detection.
DNA nanotechnology: Designed DNA devices to study molecular interactions with cell membrane functions including endocytosis, exocytosis and lysis.
Organic bioelectronics: We develop an array of organic electronic devices, translating electronic input signals to delivery of chemical subst-ances.

Project

PI

Different aspects of microfluidics
Helene Andersson Svahn
Organic bioelectronic devices
Agneta Richter-Dahlfors
Adapting the microenvironment to regulate leukocyte function
Mia Phillipson
Surface modification of polymer biomaterials
Ulrica Edlund

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