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  • 1.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Hypoxia on a chip: a novel approach for patch-clamp studies in a microfluidic system with full oxygen control2012In: World Congress on Medical Physics and Biomedical Engineering, May 26-31, 2012, Beijing, China / [ed] Mian Long, Berlin: Encyclopedia of Global Archaeology/Springer Verlag, 2012, p. 313-316Conference paper (Refereed)
    Abstract [en]

    Here a new approach to perform patch-clamp investigations under anoxic and normoxic conditions on nerve cells from Sprague Dawley rats is presented. A patch-clamp micropipette is integrated within a poly-methyl methacrylate (PMMA) based microchip giving optimal control over the oxygen content and the biochemical environment. Nerve cells were trapped by optical tweezers and steered towards the patch-clamp micropipette within the micro-channels. Several experiments were performed to show proof of principle. The oxygen content within the microfluidic chamber was measured to 0.5-1.5 %. The photo-induced effect of the optical tweezers on the nerve cells was investigated in an open Petri dish. The optical trapping did not influence measurements. The microfluidic system was further tested in patch-clamp experiments. This approach showed significant advantages regarding the tuning of the oxygen content and may be used in various electrophysiological investigations of single cells demanding optimal control of the surroundings.

  • 2.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp measurements on a chip with full control over the oxygen content2012In: Journal of Biochips & Tissue Chips, ISSN 2153-0777, Vol. 2, no 1, p. 1-5Article in journal (Refereed)
  • 3.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Development of microfluidic system and optical tweezers for electrophysiological investigations of an individual cell2010In: Optical Trapping and Optical Micromanipulation VII: 1 - 5 August 2010, San Diego, California, United States ; [part of SPIE optics + photonics] / [ed] Kishan Dholakia; Gabriel C. Spalding, Bellingham, Wash: SPIE - International Society for Optical Engineering, 2010Conference paper (Refereed)
    Abstract [en]

    We present a new approach of combining Lab-on-a-chip technologies with optical manipulation technique for accurate investigations in the field of cell biology. A general concept was to develop and combine different methods to perform advanced electrophysiological investigations of an individual living cell under optimal control of the surrounding environment. The conventional patch clamp technique was customized by modifying the open system with a gas-tight multifunctional microfluidics system and optical trapping technique (optical tweezers).The system offers possibilities to measure the electrical signaling and activity of the neuron under optimum conditions of hypoxia and anoxia while the oxygenation state is controlled optically by means of a spectroscopic technique. A cellbased microfluidics system with an integrated patch clamp pipette was developed successfully. Selectively, an individual neuron is manipulated within the microchannels of the microfluidic system under a sufficient control of the environment. Experiments were performed to manipulate single yeast cell and red blood cell (RBC) optically through the microfluidics system toward an integrated patch clamp pipette. An absorption spectrum of a single RCB was recorded which showed that laser light did not impinge on the spectroscopic spectrum of light. This is promising for further development of a complete lab-on-a-chip system for patch clamp measurements.

  • 4.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ett mikroflödessystem för multipla undersökningar av enstaka biologiska celler under hypoxiska förhållanden2011Conference paper (Refereed)
    Abstract [sv]

    Introduktion: Syftet med studien är att studera enstaka nervcellers respons vid syrebrist i ett mikroflödessystem för att förstå nervcellens respons vid stroke. Målet med studien var att utveckla ett slutet mikroflödessystem som ger optimal kontroll av den omgivande miljön och samtidigt möjliggöra elektrofysiologiska undersökningar under kontrollerade syreförhållande. Material och metoder: Mikroflödescellen utvecklades för ett inverterat mikroskop, utrustad med en optisk pincett och optisk spektroskopi samt patch-clamp för elektrofysiologiska studier på en enstaka nervcell. Istället för att föra en pipett mot en cell i ett öppet system fångades en enskild cell optiskt i ett slutet mikroflödessystem och fördes mot en fixerad patch-clamp mikropipett. Cellen utsattes för olika syrehalter och övervakades av ett UV-Vis spektroskop medan cellens elektrofysiologiska aktivitet registreras med patch-clamp. Det slutna mikroflödessystemet med integrerad mikropipett, kopplades till ett pumpsystem för införandet av celler och buffert med olika kemiska egenskaper och syrehalter. I ett inverterat mikroskop integrerades optisk pincett, UV-Vis spektrometer och patch-clamp. Resultat och diskussion: För att pröva konceptet fångades och fördes en röd blodcell optiskt mot mikropipetten som befann sig på en fast position i mikroflödescellen. Cellens syrebindningstillstånd varierades genom att tillsätta syrefri eller syresatt buffert och registrerades med UV-Vis spektrometern. I ett vidare experiment manipulerades en nervcell optiskt i ett öppet system mot patch-clamp pipetten och elektrofysiologiska mätningar utfördes. Vi kunde verifiera att den optiska pincetten inte påverkade den elektrofysiologiska mätningen. För närvarandet utförs elektrofysiologiska mätningar i det slutna mikroflödessystemet för att se hur nervcellerna reagerar under varierande syrehalt. Genom mätningarna hoppas vi att få mer kunskap om försvarsmekanismerna som igångsätts av neuroner under syrefattiga förhållanden.

  • 5. Alrifaiy, Ahmed
    et al.
    Borg, Johan
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Embedded Internet Systems Lab.
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy: first investigations of single biological cells2015In: Biomedical engineering online, ISSN 1475-925X, E-ISSN 1475-925X, Vol. 14, article id 36Article in journal (Refereed)
    Abstract [en]

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.

  • 6. Alrifaiy, Ahmed
    et al.
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ett mikroflödessystem med optisk pincett och UV- vis för studier på enskilda biologiska celler2010Conference paper (Other academic)
  • 7.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp electrophysiological measurements on single cells under hypoxic conditions in microfluidic systems2012Conference paper (Refereed)
  • 8.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Polymer-based microfluidic devices for pharmacy, biology and tissue engineering2012In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 4, no 3, p. 1349-1398Article in journal (Refereed)
    Abstract [en]

    This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  • 9.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    How to integrate a micropipette into a closed microfluidic system: absorption spectra of an optically trapped erythrocyte2011In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 2, no 8, p. 2299-2306Article in journal (Refereed)
    Abstract [en]

    In July 2011 a new concept of a closed microfluidic system equipped with a fixed micropipette, optical tweezers and a UV-Vis spectrometer was presented [Biomed. Opt. Express 2, 2299 (2011)]. Figure 1 showed falsely oriented mirrors. To clarify the design of the setup, this erratum presents a correct schematic

  • 10.
    Bitaraf, Nazanin
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Alrifaiy, Ahmed
    Luleå tekniska universitet.
    Druzin, Mikhail
    Umeå University, Department of Integrative Medical Biology, Physiology.
    Ramser, Kerstin
    Development of a multifunctional microfluidic system for studies of nerve cell activity during hypoxic and anoxic conditions2009In: World Congress on Medical Physics and Biomedical Engineering: September 7 - 12, 2009, Munich, Germany, Berlin: Springer Science+Business Media B.V., 2009, Vol. 8, p. 176-179Conference paper (Refereed)
  • 11. Bitaraf, Nazanin
    et al.
    Druzin, Mikhail
    Umeå University, Integrative Medical Biology, Physiology.
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Elektrofysiologiska mätningar på MPN-neuroner under hypoxi: ett steg mot profylaktisk behandling av patienter i riskzonen för stroke2010In: Medicinteknikdagarana 2010, 2010Conference paper (Other academic)
  • 12. Bitaraf, Nazanin
    et al.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Alrifaiy, Ahmed
    Multipla mätningar på enstaka celler i ett mikroflödessystem2009Conference paper (Other academic)
  • 13.
    Candefjord, Stefan
    et al.
    Chalmers University of Technology.
    Murayama, Yoshinobu
    College of Engineering, Nihon University.
    Nyberg, Morgan
    Hallberg, Josef
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Ljungberg, Börje
    Umeå University, Department of Surgical and Perioperative Science, Urology and Andrology.
    Bergh, Anders
    Department of Medical Biosciences Pathology, Umeå University.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterisation2012In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 36, no 6, p. 319-327Article in journal (Refereed)
    Abstract [en]

    The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterisation in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental setup combining micro-scale TRM — scanning haptic microscopy (SHM) — for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy for using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 65–81%, and when RS was added it was increased to 81–87%. The accuracy for healthy and cancerous human tissue was 67–70% when only SHM was used, and increased to 72–77% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery.

  • 14.
    Candefjord, Stefan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Nyberg, Morgan
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics.
    Ramser, Kerstin
    Lindahl, Olof
    Combining fibre optic Raman spectroscopy and tactile resonance measurement for tissue characterization2010In: Measurement science and technology, ISSN 0957-0233, E-ISSN 1361-6501, Vol. 21, no 12Article in journal (Refereed)
    Abstract [en]

    Tissue characterization is fundamental for identification of pathological conditions. Raman spectroscopy (RS) and tactile resonance measurement (TRM) are two promising techniques that measure biochemical content and stiffness, respectively. They have potential to complement the golden standard-–histological analysis. By combining RS and TRM, complementary information about tissue content can be obtained and specific drawbacks can be avoided. The aim of this study was to develop a multivariate approach to compare RS and TRM information. The approach was evaluated on measurements at the same points on porcine abdominal tissue. The measurement points were divided into five groups by multivariate analysis of the RS data. A regression analysis was performed and receiver operating characteristic (ROC) curves were used to compare the RS and TRM data. TRM identified one group efficiently (area under ROC curve 0.99). The RS data showed that the proportion of saturated fat was high in this group. The regression analysis showed that stiffness was mainly determined by the amount of fat and its composition. We concluded that RS provided additional, important information for tissue identification that was not provided by TRM alone. The results are promising for development of a method combining RS and TRM for intraoperative tissue characterization.

  • 15. Candefjord, Stefan
    et al.
    Nyberg, Morgan
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Evaluating the use of a Raman fiberoptic probe in conjunction with a resonance sensor for measuring porcine tissue in vitro2009In: World Congress on Medical Physics and Biomedical Engineering: September 7 - 12, 2009, Munich, Germany / [ed] Olaf Dössel; Wolfgang C. Schlegel, Berlin: Springer Science+Business Media B.V., 2009, Vol. 7, p. 414-417Conference paper (Refereed)
    Abstract [en]

    Prostate cancer is the most common form of cancer and the third leading cause of cancer-related death in European men. There is a need for new methods that can accurately localize and diagnose prostate cancer. In this study a new approach is presented: a combination of resonance sensor technology and Raman spectroscopy. Both methods have shown promising results for prostate cancer detection in vitro. The aim of this study was to evaluate the combined information from measurements with a Raman fiberoptic probe and a resonance sensor system. Pork belly tissue was used as a model system. A three-dimensional translation table was equipped with an in-house developed software, allowing measurements to be performed at the same point using two separate instruments. The Raman data was analyzed using principal component analysis and hierarchical clustering analysis. The spectra were divided into 5 distinct groups. The mean stiffness of each group was calculated from the resonance sensor measurements. One of the groups differed significantly (p < 0.05) from the others. A regression analysis, with the stiffness parameter as response variable and the principal component scores of the Raman data as the predictor variables, explained 67% of the total variability. The use of a smaller resonance sensor tip would probably increase the degree of correlation. In conclusion, Raman spectroscopy provides additional discriminatory power to the resonance sensor

  • 16. Candefjord, Stefan
    et al.
    Nyberg, Morgan
    Jalkanen, Ville
    Umeå universitet.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Kombinationsinstrument för detektering av prostatacancer: korrelation mellan resonanssensor och fiberoptisk Ramanprobe2009Conference paper (Other academic)
  • 17.
    Candefjord, Stefan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Lindahl, Olof
    Effects of snap-freezing and laser illumination of tissue on near-infrared Raman spectra of porcine prostate tissue2008Conference paper (Other academic)
  • 18. Candefjord, Stefan
    et al.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Effects of snap-freezing and near-infrared laser illumination on porcine prostate tissue as measured by Raman spectroscopy2009In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 134, no 9, p. 1815-1821Article in journal (Refereed)
    Abstract [en]

    Most Raman spectroscopic studies on tissue are performed in vitro. To assure that the results are applicable to in vivo examinations, preparation protocols and measurement procedures of tissue for in vitro studies should preserve tissue characteristics close to the native state. This study had two aims. The first was to elucidate if photoinduced effects arise during 5 minutes' continuous illumination of tissue with an 830 nm laser at an irradiance of 3 × 1010 W/m2. The second was to investigate the effects of snap-freezing of porcine prostate tissue in liquid nitrogen and subsequent storage at -80 °C, by means of multivariate analysis. 830 nm laser illumination of the specified irradiance did not affect the Raman spectra. A decrease of the spectral background was observed, likely due to photobleaching of tissue fluorophores. Snap-freezing and subsequent storage at -80 °C gave rise to subtle but significant alterations in Raman spectra, most likely related to changes in the protein conformations

  • 19.
    Candefjord, Stefan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Lindahl, Olof
    En ny metod för att lokalisera och diagnostisera prostatacancer2007In: Medicinteknikdagarna, 2007, p. 33-34Conference paper (Other academic)
  • 20.
    Candefjord, Stefan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Kombinationsinstrument för detektering av prostatacancer: mätningar på snitt av grisprostata med resonanssensor och fiberoptisk Ramanprobe2010Conference paper (Refereed)
  • 21. Candefjord, Stefan
    et al.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Technologies for localization and diagnosis of prostate cancer2009In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 33, no 8, p. 585-603Article in journal (Refereed)
    Abstract [en]

    The gold standard for detecting prostate cancer (PCa), systematic biopsy, lacks sensitivity as well as grading accuracy. PSA screening leads to over-treatment of many men, and it is unclear whether screening reduces PCa mortality. This review provides an understanding of the difficulties of localizing and diagnosing PCa. It summarizes recent developments of ultrasound (including elastography) and MRI, and discusses some alternative experimental techniques, such as resonance sensor technology and vibrational spectroscopy. A comparison between the different methods is presented. It is concluded that new ultrasound techniques are promising for targeted biopsy procedures, in order to detect more clinically significant cancers while reducing the number of cores. MRI advances are very promising, but MRI remains expensive and MR-guided biopsy is complex. Resonance sensor technology and vibrational spectroscopy have shown promising results in vitro. There is a need for large prospective multicentre trials that unambiguously prove the clinical benefits of these new techniques.

  • 22.
    Candefjord, Stefan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Towards new sensors for cancer detection in vivo, a handheld detector combining a bre-optic Raman probe and a resonance sensor2007Conference paper (Refereed)
  • 23. Enger, Jonas
    et al.
    Goksör, Mattias
    Ramser, Kerstin
    Hagberg, Petter
    Hanstorp, Dag
    Optical tweezers applied to a microfluidic system2004In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 4, no 3, p. 196-200Article in journal (Refereed)
    Abstract [en]

    We will demonstrate how optical tweezers can be combined with a microfluidic system to create a versatile microlaboratory. Cells are moved between reservoirs filled with different media by means of optical tweezers. We show that the cells, on a timescale of a few seconds, can be moved from one reservoir to another without the media being dragged along with them. The system is demonstrated with an experiment where we expose E. coli bacteria to different fluorescent markers. We will also discuss how the system can be used as an advanced cell sorter. It can favorably be used to sort out a small fraction of cells from a large population, in particular when advanced microscopic techniques are required to distinguish various cells. Patterns of channels and reservoirs were generated in a computer and transferred to a mask using either a sophisticated electron beam technique or a standard laser printer. Lithographic methods were applied to create microchannels in rubber silicon (PDMS). Media were transported in the channels using electroosmotic flow. The optical system consisted of a combined confocal and epi-fluorescence microscope, dual optical tweezers and a laser scalpel.

  • 24.
    Enman, Josefine
    et al.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Patra, Anuttam
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Rova, Ulrika
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Berglund, Kris
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Solid state characterization of sodium eritadenate2011In: American Journal of Analytical Chemistry, ISSN 2156-8251, E-ISSN 2156-8278, Vol. 2, no 2, p. 164-173Article in journal (Refereed)
    Abstract [en]

    Knowledge of the solid state is of great importance in the development of a new active pharmaceutical ingredient, since the solid form often dictates the properties and performance of the drug. In the present study, solid state characteristics of the sodium salt of the candidate cholesterol reducing compound eritadenine, 2(R), 3(R))-dihydroxy-4-(9-adenyl)-butanoic acid, were investigated. The compound was crystallized by slow cooling from water and various aqueous ethanol solutions, at different temperatures. Further, the compound solution was subjected to lyophilization and to high vacuum drying. The resulting solids were screened for polymorphism by micro Raman spectroscopy (λex = 830 nm) and the crystallinity was investigated by X-ray powder diffraction. Further, thermal analysis was applied to study possible occurrence of solvates or hydrates. Solids obtained from slow cooling showed crystallinity, whereas rapid cooling gave rise to more amorphous solids. Analysis of difference spectra of the Raman data for solids obtained from slow cooling of solution revealed subtle differences in the structures between crystals derived from pure water and crystals derived from aqueous ethanol solutions. Finally, from the thermal analysis it was deduced that crystals obtained from pure water were stoichiometrically dihydrates whereas crystals obtained from aqueous ethanol solutions were 2.5 hydrates; this formation of different hydrates were supported by the Raman difference analysis.

  • 25.
    Enman, Josefine
    et al.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Rova, Ulrika
    Berglund, Kris
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Raman analysis of synthetic eritadenine2008In: Journal of Raman Spectroscopy, ISSN 0377-0486, E-ISSN 1097-4555, Vol. 39, no 10, p. 1464-1468Article in journal (Refereed)
    Abstract [en]

    Eritadenine, 2(R),3(R)-dihydroxy-4-(9-adenyl)-butyric acid, is a cholesterol-reducing compound naturally occurring in the shitake mushroom (Lentinus edodes). To identify the unknown Raman spectrum of this compound, pure synthetic eritadenine was examined and the vibrational modes were assigned by following the synthesis pathway. This was accomplished by comparing the known spectra of the starting compounds adenine and D-ribose with the spectra of a synthesis intermediate, methyl 5-(6-Aminopurin-9H-9-yl)-2,3-O-isopropylidene-5-deoxy-β-D-ribofuranoside (MAIR) and eritadenine. In the Raman spectrum of eritadenine, a distinctive vibrational mode at 773 cm-1 was detected and ascribed to vibrations in the carbon chain, ν(C--C). A Raman line that arose at 1212 cm-1, both in the Raman spectrum of MAIR and eritadenine, was also assigned to ν(C--C). Additional Raman lines detected at 1526 and at 1583 cm-1 in the Raman spectrum of MAIR and eritadenine were assigned to ν(N--C) and a deformation of the purine ring structure. In these cases the vibrational modes are due to the linkage between adenine and the ribofuranoside moiety for MAIR, and between adenine and the carbon chain for eritadenine. This link is also the cause for the disappearance of adenine specific Raman lines in the spectrum of both MAIR and eritadenine. Several vibrations observed in the spectrum of D-ribose were not observed in the Raman spectrum of eritadenine due to the absence of the ribose ring structure. In the Raman spectrum of MAIR some of the D-ribose specific Raman lines disappeared due to the introduction of methyl and isopropylidene moieties to the ribose unit. With the approach presented in this study the so far unknown Raman spectrum of eritadenine could be successfully identified and is presented here for the first time.

  • 26. Eriksson, Emma
    et al.
    Enger, Jonas
    Nordlander, Bodil
    Erjavec, Nika
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Goskör, Mattias
    Hohmann, Stefan
    Nyström, Thomas
    Hanstorp, Dag
    A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes2007In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 7, p. 71-76Article in journal (Refereed)
    Abstract [en]

    We report on the development of an experimental platform where epi-fluorescence microscopy and optical tweezers are combined with a microfluidic system to enable the analysis of rapid cytological responses in single cells. The microfluidic system allows two different media to be merged in a Y-shaped channel. Microscale channel dimensions ensure purely laminar flow and, as a result, an environmental gradient can be created between the two media. Optical tweezers are used to move a single trapped cell repeatedly between the different environments. The cell is monitored continuously by fluorescence microscopy during the experiment. In a first experiment on yeast (Saccharomyces cerevisiae) we observed changes in cell volume as the cell was moved between environments with different osmolarity. This demonstrated that the platform allowed analysis of cytological alterations on a time scale shorter than 0.2 s. In a second experiment we observed the spatial migration of the Yap1p transcription factor fused to GFP as a cell was moved from an environment of low to high oxidative capacity. The system is universal allowing the response to numerous environmental changes to be studied on the sub second time scale in a variety of model cells. We intend to use the platform to study how the age of cells, their progression through the cell cycle, or their genetic landscape, alter their capacity (kinetics and amplitude) to respond to environmental changes.

  • 27.
    Eriksson, Emma
    et al.
    Physics Department, Göteborg University.
    Scrimgeour, Jan
    Physics Department, Göteborg University.
    Granéli, Annette
    Physics Department, Göteborg University.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Wellander, Rikard
    Physics Department, Göteborg University.
    Enger, Jonas
    Physics Department, Göteborg University.
    Hanstorp, Dag
    Physics Department, Göteborg University.
    Goksör, Mattias
    Physics Department, Göteborg University.
    Optical manipulation and microfluidics for studies of single cell dynamics2007In: Journal of Optics. A, Pure and applied optics, ISSN 1464-4258, E-ISSN 1741-3567, Vol. 9, no 8, p. 113-121Article in journal (Refereed)
    Abstract [en]

    Most research on optical manipulation aims towards investigation and development of the system itself. In this paper we show how optical manipulation, imaging and microfluidics can be combined for investigations of single cells. Microfluidic systems have been fabricated and are used, in combination with optical tweezers, to enable environmental changes for single cells. The environment within the microfluidic system has been modelled to ensure control of the process. Three biological model systems have been studied with different combinations of optical manipulation, imaging techniques and microfluidics. In Saccharomyces cerevisiae, environmentally induced size modulations and spatial localization of proteins have been studied to elucidate various signalling pathways. In a similar manner the oxygenation cycle of single red blood cells was triggered and mapped using Raman spectroscopy. In the third experiment the forces between the endoplasmic reticulum and chloroplasts were studied in Pisum sativum and Arabidopsis thaliana. By combining different techniques we make advanced biological research possible, revealing information on a cellular level that is impossible to obtain with traditional techniques.

  • 28.
    Erjavec, Nika
    et al.
    CBZI, University of Nova Gorica, Vipava.
    Pinato, Giulietta
    CBZI, University of Nova Gorica, Vipava.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Raman spectroscopy as a tool for detecting mitochondrial fitness2016In: Journal of Raman Spectroscopy, ISSN 0377-0486, E-ISSN 1097-4555, Vol. 47, no 8, p. 933-939Article in journal (Refereed)
    Abstract [en]

    Raman spectroscopy allows the molecular chemical analysis of whole living cells by comparing them to known Raman signatures of specific vibrational bonds. In this work we used Raman spectroscopy to differentiate between wild type yeast cells and mutants characterized by increased or reduced mitochondrial fragmentation. To associate mitochondrial fragmentation with biochemical markers, we performed Linear Discriminant Analysis (LDA) of whole cell Raman spectra (~50–100 cells/spectrum). We show that the long-lived, less fragmented mutants fall into a significantly distant cluster from the wild type and short-lived, more fragmented mutants. Clustering depends on respiratory growth and coincides with that of membrane phospholipids and some respiratory chain components. Spectral clustering is supported by enzymatic activity measurements of OXPHOS Complexes. In addition, we find that NAD(P)H autofluorescence also correlates with mitochondrial fragmentation, representing another likely aging biomarker, besides phospholipids and OXPHOS components. In summary, we demonstrate that Raman spectroscopy has the potential to become a powerful tool for differentiating healthy from unhealthy aged tissues, as well as for the prognostic evaluation of mitochondrial function and fitness.

  • 29. Goskor, Mattias
    et al.
    Enger, Jonas
    Ramser, Kerstin
    Hanstorp, Dag
    An experimental set-up for combining optical tweezers and laser scalpels with advanced imaging techniques2003In: Microarrays and Combinatorial Technologies for Biomedical Applications: Design, Fabrication, and Analysis / [ed] Dan V. Nicolau; Ramesh Raghavachari, Bellingham, Wash: SPIE - International Society for Optical Engineering, 2003, p. 50-57Conference paper (Refereed)
    Abstract [en]

    In this paper we will describe a system designed to combine optical tweezers and laser scalpels with confocal as well as epi-fluorescence microscopy. A continuos wave Nd:YVO4 laser is used to produce a dual optical tweezers, where each trap can be individually controlled. A second optical tweezers setup is based on a tunable titanium sapphire laser, which allows us to adjust the wavelength to minimize the damage to the cell under investigation. A pulsed nitrogen laser working at 337 nm forms a laser scalpel. The tweezers and scalpels are both incorporated in an inverted microscope equipped with epi-fluorescence and confocal imaging capabilities. In order to further control the sample we have developed a technique to tailor make the environment closest to the studied objects. Micrometer-sized structures such as channels and reservoirs have been produced in rubber silicon using lithographic methods. In combination with a micro-manipulator, our system can be used to extract single cells from a population of billions for further studies or growth.

  • 30. Granéli, Annette
    et al.
    Eriksson, Emma
    Enger, Jonas
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Goksör, Mattias
    Hohmann, Stefan
    Hanstorp, Dag
    A microfluidic system for studies of stress response in single cells using optical tweezers2006In: Optical trapping and optical micromanipulation III: 13 - 17 August 2006, San Diego, California, USA / [ed] Kishan Dholakia; Gabriel C. Spalding, Bellingham, Wash.: SPIE - International Society for Optical Engineering, 2006Conference paper (Refereed)
    Abstract [en]

    In recent years there has been a growing interest in the use of optical manipulation techniques, such as optical tweezers, in biological research as the full potential of such applications are being realized. Biological research is developing towards the study of single entities to reveal new behaviors that cannot be discovered with more traditional ensemble techniques. To be able to study single cells we have developed a new method where a combination of micro-fluidics and optical tweezers was used. Micro-fluidic channels were fabricated using soft lithography. The channels consisted of a Y-shaped junction were two channels merged into one. By flowing different media in the two channels in laminar flow we were able to create a sharp concentration gradient at the junction. Single cells were trapped by the tweezers and the micro-fluidic system allowed fast environmental changes to be made for the cell in a reversible manner. The time required to change the surroundings of the cell was limited to how sharp mixing region the system could create, thus how far the cells had to be moved using the optical tweezers. With this new technique cellular response in single cells upon fast environmental changes could be investigated in real time. The cellular response was detected by monitoring variations in the cell by following the localization of fluorescently tagged proteins within the cell.

  • 31.
    Jansson, Helén
    et al.
    Chalmers University of Technology, Department of Civil and Environmental Engineering.
    Bernin, Diana
    Swedish NMR Centre, Gothenburg University.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Silicate species of water glass and insights for alkali-activated green cement2015In: AIP Advances, ISSN 2158-3226, E-ISSN 2158-3226, Vol. 5, no 6, article id 67167Article in journal (Refereed)
    Abstract [en]

    Despite that sodium silicate solutions of high pH are commonly used in industrial applications, most investigations are focused on low to medium values of pH. Therefore we have investigated such solutions in a broad modulus range and up to high pH values (similar to 14) by use of infrared (IR) spectroscopy and silicon nuclear magnetic resonance (Si-29-NMR). The results show that the modulus dependent pH value leads to more or less charged species, which affects the configurations of the silicate units. This in turn, influences the alkali-activation process of low CO2 footprint cements, i.e. materials based on industrial waste or by-products

  • 32.
    Jansson, Helén
    et al.
    Chalmers University of Technology, Department of Civil and Environmental Engineering.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Bernin, Diana
    Swedish NMR.
    Tang, Luping
    Chalmers University of Technology, Department of Civil and Environmental Engineering.
    The influence of silica species configuration on the hydration of alkali-activated ground granulated blast-furnace slag2014In: Second International Conference on Advances in Chemically-Activated Materials: CAM'2014, Changsha, Hunan, China, June 1 - 3, 2014 / [ed] C. Shi; X. Shen, Bagneux: Rilem publications, 2014, p. 309-318Conference paper (Refereed)
    Abstract [en]

    There are indications on that the initial setting time is dependent on the relative ratio of Na2O to SiO2 when sodium silicate solutions (Na2SiO3) are used for the alkali-activation of ground granulated blast-furnace slag (GGBS). One possible reason for this is that the ratio (called modulus) not only influences the pH but also the viscosity of the solution. The viscosity is, in turn dependent on the structures in the liquid. Therefore, we have investigated the structure of sodium silicate solutions of different moduli by infrared spectroscopy (IR) and silicon nuclear magnetic resonance (Si-29-NMR). The results, which show that the silica configuration is highly dependent on the modulus, will be discussed in relation to the initial setting time of corresponding measurements on GGBS hydration

  • 33.
    Knoepp, F.
    et al.
    Justus Liebig University Giessen.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Weissmann, N.
    Justus Liebig University Giessen.
    Hypoxia alters the redox state and inhibits K+-currents in mouse pulmonary arterial smooth muscle cells2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no S711, p. 139-Article in journal (Refereed)
  • 34.
    Knoepp, F.
    et al.
    Excellence-Cluster Cardio-Pulmonary System (ECCPS), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, Giessen, Germany.
    Wahl, Joel
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Andersson, Anders G.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Borg, J.
    CMS, Imperial College, London, UK.
    Weissmann, N.
    Excellence-Cluster Cardio-Pulmonary System (ECCPS), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, D-35392 Giessen, Germany.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Development of a Gas-Tight Microfluidic System for Raman Sensing of Single Pulmonary Arterial Smooth Muscle Cells Under Normoxic/Hypoxic Conditions2018In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 10, article id 3238Article in journal (Refereed)
    Abstract [en]

    Acute hypoxia changes the redox-state of pulmonary arterial smooth muscle cells (PASMCs). This might influence the activity of redox-sensitive voltage-gated K⁺-channels (Kv-channels) whose inhibition initiates hypoxic pulmonary vasoconstriction (HPV). However, the molecular mechanism of how hypoxia-or the subsequent change in the cellular redox-state-inhibits Kv-channels remains elusive. For this purpose, a new multifunctional gas-tight microfluidic system was developed enabling simultaneous single-cell Raman spectroscopic studies (to sense the redox-state under normoxic/hypoxic conditions) and patch-clamp experiments (to study the Kv-channel activity). The performance of the system was tested by optically recording the O₂-content and taking Raman spectra on murine PASMCs under normoxic/hypoxic conditions or in the presence of H₂O₂. Oxygen sensing showed that hypoxic levels in the gas-tight microfluidic system were achieved faster, more stable and significantly lower compared to a conventional open system (1.6 ± 0.2%, respectively 6.7 ± 0.7%, n = 6, p < 0.001). Raman spectra revealed that the redistribution of biomarkers (cytochromes, FeS, myoglobin and NADH) under hypoxic/normoxic conditions were improved in the gas-tight microfluidic system (p-values from 0.00% to 16.30%) compared to the open system (p-value from 0.01% to 98.42%). In conclusion, the new redox sensor holds promise for future experiments that may elucidate the role of Kv-channels during HPV.

  • 35.
    Lianming, Tong
    et al.
    Department of Applied Physics, Chalmers University of Technology.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Käll, Mikael
    Department of Applied Physics, Chalmers University of Technology.
    Optical tweezers for Raman spectroscopy2012In: Raman Spectroscopy for Nanomaterials Characterization, Berlin Heidelberg: Encyclopedia of Global Archaeology/Springer Verlag, 2012, 1, p. 507-530Chapter in book (Refereed)
  • 36.
    Lindahl, Olof A.
    et al.
    Department of Radiation Sciences, Biomedical Engineering, Umeå University.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Bäcklund, Tomas
    Department of Radiation Sciences, Biomedical Engineering, Umeå University.
    Ljungberg, Börje
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University.
    Bergh, Anders
    Department of Medical Bioscience, Pathology, Umeå University.
    Prostate cancer detection ex vivo combining Raman spectroscopy and tactile resonance technology2017In: EMBEC & NBC 2017: Joint Conference of the European Medical and Biological Engineering Conference (EMBEC) and the Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC), Tampere, Finland, June 2017 / [ed] Hannu Eskola, Outi Väisänen, Jari Viik, Jari Hyttinen, Singapore: Springer, 2017, p. 193-196Conference paper (Refereed)
    Abstract [en]

    Prostate cancer is the most common cancer for men in the western world. The most prevalent curative treatment is radical prostatectomy. However, prostate surgery can give unwanted side effects and there is a need for an instrument that can provide decision support to the surgeon during surgery on the presence of cancer cells in the surgical margin. A dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for detecting cancer in fresh human prostate tissue. The tactile resonance modality measures the tissue stiffness and Raman spectroscopy depicts the molecular content in tissue, both related to cancer. After ethical approval, the study investigated the potential of the dual-modality probe by testing its ability to differentiate between normal and cancerous prostate tissue ex vivo. It also investigated the minimal amount of measurement points needed to securely detect cancer on the surface of prostate tissue. Measurements on three prostate tissue slices show that the tactile resonance modality measuring stiffness was able to detect differences between normal and cancerous tissue on a significant level of 90%, but the sample size was too low to draw any firm conclusions. It was also suggested from the study results that the high wavenumber region in the Raman spectrum can give valuable information about cancer in prostate tissue. A number of 24 measurement points were enough for detecting cancer in prostate slices in this study. It can be suggested from this study that combining these two sensor modalities is promising for accurate detection of prostate cancer that is needed during prostate surgery, but more measurements including more prostates must be performed before the full value of the study result can be established.

  • 37. Lindahl, Olof
    et al.
    Andersson, B.
    Umeå universitet.
    Lundström, R.
    Umeå universitet.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    From biomedical research to spin-off companies for the health care market2010In: XIIth Mediterranean Conference on Medical and Biological Engineering and Computing 2010: [MEDICON 2010] ; May 27 - 30, 2010, Chalkidiki, Greece / [ed] Panagiotis D. Bamidis; Nicolas Pallikarakis, Berlin: Springer Science+Business Media B.V., 2010, p. 624-626Conference paper (Refereed)
    Abstract [en]

    Through research at the centre for biomedical engineering and physics (CMTF) seven new companies have been established in Northern Sweden. The activities have generated growth both in academia at the universities and in the industry in Northern Sweden. Cooperation was built up between the 23 research projects and more than 20 established companies in the field of biomedical engineering. A researcher-owned company for business development of the research results from the CMTF has been established, CMTF Business Development Co Ltd, and has launched its first spin-off company in the autumn 2009. It has also increased the interest for commercial and entrepreneurship questions among the scientists in the centre. So far seven spin-off companies have resulted from the CMTF-research.

  • 38.
    Lindahl, Olof
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Andersson, B.M.
    Centre for Biomedical Engineering and Physics, Umeå University.
    Lundström, R.
    Centre for Biomedical Engineering and Physics, Umeå University.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Biomedical engineering research improves the health care industry2013In: XIII Mediterranean conference on medical and biological engineering and computing: MEDICON 2013, 25-28 September 2013, Seville, Spain / [ed] Laura M. Roa Romero, Wien: Encyclopedia of Global Archaeology/Springer Verlag, 2013, Vol. VIII, p. 1124-1126Conference paper (Refereed)
    Abstract [en]

    The health care industry is dependent on new innovations for its survival and expansion. Health care innovations are also important for improving patient care. Through activities at the centre for biomedical engineering and physics (CMTF) we have generated growth both in academia at the universities and in the industry in northern Sweden. Fruitful cooperation was generated between 26 research projects and about 15 established companies in the field of biomedical engineering. The established researcher-owned company for business development of the research results from the CMTF, CMTF Business Development Co Ltd, has so far launched three spin-off companies and has 10 new business leads to develop. The activities have also increased the interest for commercialization and entrepreneurship among the scientists in the centre. So far a total of nine spin-off companies have resulted from the CMTF-research since the year 2000 that has improved the health care market in northern Sweden

  • 39.
    Lindahl, Olof
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Andersson, Britt
    Institutet för tillämpad fysik och elektronik, Umeå universitet.
    Karlsson, Stefan
    Medicinsk teknik, NUS, Umeå.
    Lundström, Ronnie
    Medicinsk teknik, NUS, Umeå.
    Ramser, Kerstin
    Från forskningsidé till kommersiell produkt på marknaden: CMTF, ett framgångsexempel2009Conference paper (Other academic)
  • 40.
    Lindahl, Olof
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Department of Radiation Sciences, Umeå University, Centrum för medicinsk teknik och fysik (CMTF).
    Nyberg, Morgan
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics, Centrum för medicinsk teknik och fysik (CMTF).
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Centrum för medicinsk teknik och fysik (CMTF).
    Erratum: Prostate cancer detection using a combination of Raman spectroscopy and stiffness sensing2014In: 1st Global Conference on Biomedical Engineering & 9th Asian-Pacific Conference on Medical and Biological Engineering: October 9-12, 2014, Tainan, Taiwan / [ed] Fong-Chin Su; Shyh-Hau Wang; Ming-Long Yeh, New York: Encyclopedia of Global Archaeology/Springer Verlag, 2014, p. e1-Conference paper (Refereed)
    Abstract [en]

    IFMBE Proceedings Vol. 47: ”1st Global Conference on Biomedical Engineering & 9th Asian-Pacific Conference on Medical and Biological Engineering” missed the contribution ”Prostate cancer detection using a combination of Raman spectroscopy and stiffness sensing” written by Olof Lindahl for technical reasons. The editors apologize for the mistake.

  • 41.
    Lindahl, Olof
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Department of Radiation Sciences, Umeå University, Centrum för medicinsk teknik och fysik (CMTF).
    Nyberg, Morgan
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics, Centrum för medicinsk teknik och fysik (CMTF).
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics. Centrum för medicinsk teknik och fysik (CMTF).
    Prostate cancer detection using a combination of Raman spectroscopy and stiffness sensing2014In: 1st Global Conference on Biomedical Engineering & 9th Asian-Pacific Conference on Medical and Biological Engineering: October 9-12, 2014, Tainan, Taiwan / [ed] Fong-Chin Su; Shyh-Hau Wang; Ming-Long Yeh, New York: Encyclopedia of Global Archaeology/Springer Verlag, 2014, p. 267-270Conference paper (Refereed)
    Abstract [en]

    Prostate cancer (PCa) is the most common cancer form for men in Europe. A sensor system combining Raman spectroscopy and stiffness sensing with a resonance sensor has recently been developed by us for prostate cancer detection. In this study the sensor system has been used for measurements on two slices of fresh human prostate tissue. The stiffness sensor could detect locations slices with significantly different stiffness contrasts (p < 0.05). Raman spectroscopic measurements could be performed with the dual-modality probe for tissue classification. The findings are important for the continued development of a combination probe for prostate cancer detection

  • 42.
    Nyberg, Morgan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Candefjord, Stefan
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    A combined tactile and Raman probe for tissue characterization: design considerations2012In: Measurement science and technology, ISSN 0957-0233, E-ISSN 1361-6501, Vol. 23, no 6Article in journal (Refereed)
    Abstract [en]

    Histopathology is the golden standard for cancer diagnosis and involves the characterization of tissue components. It is labour intensive and time consuming. We have earlier proposed a combined fibre-optic near-infrared Raman spectroscopy (NIR-RS) and tactile resonance method (TRM) probe for detecting positive surgical margins as a complement to interoperative histopathology. The aims of this study were to investigate the effects of attaching an RS probe inside a cylindrical TRM sensor and to investigate how laser-induced heating of the fibre-optic NIR-RS affected the temperature of the RS probe tip and an encasing TRM sensor. In addition, the possibility to perform fibre-optic NIR-RS in a well-lit environment was investigated. A small amount of rubber latex was preferable for attaching the thin RS probe inside the TRM sensor. The temperature rise of the TRM sensor due to a fibre-optic NIR-RS at 270 mW during 20 s was less than 2 °C. Fibre-optic NIR-RS was feasible in a dimmed bright environment using a small light shield and automatic subtraction of a pre-recorded contaminant spectrum. The results are promising for a combined probe for tissue characterization.

  • 43. Nyberg, Morgan
    et al.
    Jalkanen, Ville
    Umeå University. Department of Applied Physics and Electronics, Umeå universitet.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Ljungberg, Börje
    Umeå University, Department of Surgical and Perioperative Science, Urology and Andrology.
    Bergh, Anders
    Umeå University, Department of Physiology, Umeå University, Department of Medical Biosciences, Pathology, Umeå University Hospital, Department of Biomedical Engineering.
    Lindahl, Olof
    Dual-modality probe intended for prostate cancer detection combining Raman spectroscopy and tactile resonance technology—discrimination of normal human prostate tissues ex vivo2015In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 39, no 3, p. 198-207Article in journal (Refereed)
    Abstract [en]

    Prostate cancer is the most common cancer for men in the western world. For the first time, a dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for assessment of fresh human prostate tissue. The study investigates the potential of the dual-modality probe by testing its ability to differentiate prostate tissue types ex vivo. Measurements on four prostates show that the tactile resonance modality was able to discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman spectra exhibited a strong fluorescent background at the current experimental settings. However, stroma could be discerned from epithelia by integrating the value of the spectral background. Combining both parameters by a stepwise analysis resulted in 100% sensitivity and 91% specificity. Although no cancer tissue was analysed, the results are promising for further development of the instrument and method for discriminating prostate tissues and cancer

  • 44. Nyberg, Morgan
    et al.
    Ramser, Kerstin
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Cancer detection probe combining Raman and resonance sensor technology: experimental study on temperature dependence and effects of molding2009In: World Congress on Medical Physics and Biomedical Engineering: September 7 - 12, 2009, Munich, Germany / [ed] Olaf Dössel; Wolfgang C. Schlegel, Berlin: Springer Science+Business Media B.V., 2009, Vol. 7, p. 331-334Conference paper (Refereed)
    Abstract [en]

    Prostate cancer is a major health problem among men in Europe and the USA. Tactile resonance technology and Raman spectroscopy have both shown promising results in vitro, detecting and diagnosing cancer tumors respectively. A new approach, combining the strength of resonance technology and Raman spectroscopy is investigated. This study deals with the effects of molding a Raman fiber optic probe into a cylindrical resonance sensor element (RSE) to achieve a combined probe. Heat induced by the Raman spectroscopy laser might affect temperature dependent properties of the RSE. Also, molding a Raman probe into a RSE will affect its properties. The RSE temperature dependency was investigated using the resonance sensor system Venustron®. The Raman fiber optic probe was simulated by a thin steel pipe which was molded into a single cylindrical RSE. The effects on the frequency characteristics when modifying the RSE were investigated with a network analyzer. Although the resonance frequency of a RSE is temperature dependent, the frequency shift, as used for calculating stiffness, is not noticeably affected by moderate temperature variations. The RSE properties change less by using a small amount of filler material and a small diameter of the Raman probe.

  • 45. Nyberg, Morgan
    et al.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Kombinationsinstrument för detektering av prostatacancer: effekter vid ingjutning av Ramanprobe i resonanssensor och temperaturberoende2009Conference paper (Other academic)
    Abstract [sv]

    Kombinationsinstrument för detektering av prostatacancer – effekter vid ingjutning av Ramanprobe i resonanssensor och temperaturberoendeMorgan Nyberg Doktorand Institutionen för systemteknik, Luleå tekniska universitetKerstin Ramser Universitetslektor Institutionen för systemteknik, Luleå tekniska universitetOlof A. Lindahl Professor Institutionen för systemteknik, Luleå tekniska universitetBakgrundProstatacancer är den cancer som orsakar flest dödsfall bland svenska män. Nya metoder för att detektera och lokalisera prostatatumörer behövs eftersom inga pålitliga metoder finns. Vår avsikt var att utveckla ett nytt instrument som kombinerar resonanssensorteknik och Ramanspektroskopi. Det skulle möjliggöra att detektera och diagnostisera tumörer direkt vid patientundersökningar, vilket minskar risken för komplikationer. Båda teknikerna har visat lovande resultat in vitro. Resonanssensorelement (RSE) består av piezoelektriska kristaller. Förändringen i resonansfrekvens (Δf) för RSE när det kommer i kontakt med ett objekt visar objektets styvhet. Avvikande styvhet kan bero på en tumör. Ramanspektroskopi är en optisk metod som ger information om molekylärt innehåll och förändringar, som kan identifiera cancer. Idén är att integrera en endoskopiskt utformad Ramanprobe som innehåller optiska fibrer i ett cylindriskt ihåligt RSE. I denna studie undersöktes hur kombinationsinstrumentet bäst skall utformas för att undvika förlust i känslighet av RSE:t. Resonansfrekvensen för piezoelektriska material är temperaturberoende. Ett kliniskt instrument används i miljöer med varierande temperatur. Här undersöktes hur detta påverkar förmågan att avgöra styvhet.MetodEffekterna på Δf undersöktes då tunna stålrör (Ø 0,8 mm och Ø 1,2 mm) gjöts in i ett rörformat RSE (l = 15 mm, Øy = 5 mm Øi = 2,8 mm) med kautchuk (Wacker Elastosil RT622, Wacker Chemie GmbH, München, Tyskland). Effekten av mängden gjutmassa uppmättes genom att jämföra hel och halv fyllnad. Effekter av temperaturvariation på Δf undersöktes med ett resonanssystem Venustron® (Axiom Co. Ltd., Koriyama Fukushima, Japan). Mätningarna genomfördes på silikonplatta. I ena fallet varierades hela uppställningens temperatur, i det andra varierades silikonplattans temperatur så övrig utrustning hölls rumstempererad.ResultatResonansfrekvensen och signalkvaliteten förändrades minst med tunnaste stålröret samt med minsta mängden gjutmassa. Största skillnaden i Δf uppmättes till 20,7 Hz vid 1,00 mm djup då hela uppställningens temperatur varierades (22,7°C – 28,4°C). Det är i linje med storleken på feluppskattningarna i tidigare undersökningar gjorda med resonanssensorteknik i rumstemperatur.SammanfattningDenna studie visar på att integration av Raman probe i RSE med bibehållen förmåga att avläsa styvhet är möjlig om man väljer en god metod samt att RSE har försumbar temperaturdrift vid måttliga temperaturvariationer.

  • 46.
    Nyberg, Morgan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Optical fibre probe NIR Raman measurements in ambient light and in combination with a tactile resonance sensor for possible cancer detection2013In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 138, no 14, p. 4029-4034Article in journal (Refereed)
  • 47.
    Phounglamcheik, Aekjuthon
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Energy Science.
    Wang, Liang
    SINTEF Energy Research .
    Romar, Henrik
    University of Oulu, Research Unit of Applied Chemistry.
    Broström, Markus
    Umeå University, Department of Applied Physics and Electronics.
    Ramser, Kerstin
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Fluid and Experimental Mechanics.
    Skreiberg, Øyvind
    SINTEF Energy Research .
    Umeki, Kentaro
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Energy Science.
    Effects of pyrolysis oil recycling and reaction gas atmosphere on the physical properties and reactivity of charcoal from wood2018Conference paper (Refereed)
  • 48.
    Prikulis, Juris
    et al.
    Chalmers University of Technology.
    Svedberg, Fredrik
    Chalmers University of Technology.
    Käll, Mikael
    Chalmers University of Technology.
    Enger, Jonas
    Chalmers University of Technology.
    Ramser, Kerstin
    Goksör, Mattias
    Chalmers University of Technology.
    Hanstorp, Dag
    Chalmers University of Technology.
    Optical spectroscopy of single trapped metal nanoparticles in solution2004In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 4, no 1, p. 115-118Article in journal (Refereed)
    Abstract [en]

    We present a simple method for the optical manipulation and spectroscopy of colloidal silver nanoparticles in aqueous solution using optical tweezers combined with dark-field microscopy. Because of their localized plasmon resonances, single trapped metal nanoparticles can be used as efficient near-field optical probes, with potential applicability in surface-enhanced spectroscopy, near-field microscopy, and biochemical sensing schemes. As a proof of principle, we study the near-field optical interaction between a trapped and an immobilized Ag nanoparticle.

  • 49. Ramser, Kerstin
    Optical manipulation and spectroscopy of single cells and silver nanoparticles in solution2003Licentiate thesis, comprehensive summary (Other academic)
  • 50. Ramser, Kerstin
    Optical manipulation and spectroscopy of single functional globin-containing cells in microfluidic systems2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Recent advances in microbiology and biomedicine require development of tools to monitor the response of single cells to environmental stimuli under controlled physiological conditions. In this thesis, I describe how this can be achieved by combining various spectroscopic techniques with optical tweezers and microfluidic systems. Apart from absorption spectroscopy the technique of resonance Raman microscopy has been used to examine the oxygenation cycle of optically trapped cells containing heme-proteins, i.e. hemoglobin in red blood cells, neuroglobin overexpressed in Escherichia coli bacteria, and the nerve globin of the polychaete annelid Aphrodite aculeate in the ganglia of the nerve chain. Resonance Raman spectroscopy is an excellent tool to investigate the structure-function relationship of heme proteins. The porphyrin group in the heme absorbs visible light and a resonance effect leads to a selective enhancement of the porphyrin vibrations, hence, the method gives information about the oxygenation as well as the spin state of the heme iron. An important issue in the field of biochemistry, biomedicine and drug discovery is the mimicking of in vivo conditions in an in vitro environment. There is a demand to monitor chemical reactions in real time with good control over the diffusion of substances. Microfluidic technology can fulfil many of these requirements. Within this work, I developed a microfluidic system equipped with a pump that is connected to a switch enabling the flushing of buffers purged with O2 or N2 to create aerobic or anaerobic conditions in a flow cell. By doing so, I was able to monitor the oxygenation cycle of heme proteins reversibly over an extended period of time, confirming that the set-up meets the demand of physiological conditions.

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