Resonance-based contact-impedance measurement refers to the application of resonance sensors based on the measurement of the changes in the resonance curve of an ultrasonic resonator in contact with a surface. The advantage of the resonance sensor is that it is very sensitive to small changes in the contact impedance. A sensitive micro tactile sensor (MTS) was developed, which measured the elasticity of soft living tissues at the single-cell level. In the present paper, we studied the method of improving the touch and stiffness sensitivity of the MTS. First, the dependence of touch sensitivity in relation to the resonator length was studied by calculating the sensitivity coefficient at each length ranging from 9 to 40 mm. The highest touch sensitivity was obtained with a 30-mm-long glass needle driven at a resonance frequency of 100 kHz. Next, the numerical calculation of contact impedance showed that the highest stiffness sensitivity was achieved when the driving frequency was 100 kHz and the contact-tip diameter of the MTS was 10 μm. The theoretical model was then confirmed experimentally using a phase-locked-loop-based digital feedback oscillation circuit. It was found that the developed MTS, whose resonant frequency was 97.030 kHz, performed with the highest sensitivity of 53.2 × 10⁶ Hz/N at the driving frequency of 97.986 kHz, i.e. the highest sensitivity was achieved at 956 Hz above the resonant frequency.

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.

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

Background: Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the perifery of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose, a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms. Methods: With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours. Results: Measurements on the silicone samples detected the hidden stiffer object at a depth of 1 - 4 mm with a difference in the stiffness parameter of 80 - 900 mN/kHz (p < 0.028, n = 48). At the depth 5 - 6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24). Conclusion: This model study suggests that, with only a small impression depth of ≤1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.

To gain an understanding of the high-frequency elastic properties of silicone rubber, a finite element model of a cylindrical piezoelectric element, in contact with a silicone rubber disk, was constructed. The frequency-dependent elastic modulus of the silicone rubber was modeled by a fourparameter fractional derivative viscoelastic model in the 100 to 250 kHz frequency range. The calculations were carried out in the range of the first radial resonance frequency of the sensor. At the resonance, the hyperelastic effect of the silicone rubber was modeled by a hyperelastic compensating function. The calculated response was matched to the measured response by using the transitional peaks in the impedance spectrum that originates from the switching of standing Lamb wave modes in the silicone rubber. To validate the results, the impedance responses of three 5-mm-thick silicone rubber disks, with different radial lengths, were measured. The calculated and measured transitional frequencies have been compared in detail. The comparison showed very good agreement, with average relative differences of 0.7%, 0.6%, and 0.7% for the silicone rubber samples with radial lengths of 38.0, 21.4, and 11.0 mm, respectively. The average complex elastic moduli of the samples were (0.97 + 0.009i) GPa at 100 kHz and (0.97 + 0.005i) GPa at 250 kHz.

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.

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

På senare tid har aktuell forskning gett inblick i hur vår kropp fungerar på den biokemiska nivån. Det har lett till nya terapeutiska strategier för att förhindra eller bota neurologiska sjukdomar såsom hjärncancer, stroke, Alzheimers och Parkinsons. Framstegen beror till stor grad på utvecklandet av mätmetoder som ger kunskap om hur små organismer beter sig på den biomolekylära nivån. Vår tvärvetenskapliga forskning är inriktad på att utveckla metoder för att undersöka hur levande biologiska neuroner eller hjärnvävnad försvarar sig mot syrebrist eller andra stressituationer. Vi har inriktat oss på hemoproteiner då det nyligen har visat sig att de kan förhindra skador som uppstår vid syrebrist. Vi sammankopplar ett flertal mätmetoder och ett mikroflödessystem under ett mikroskop för att undersöka hemoproteiners verkan på enstaka neuroner i nära fysiologiska miljöer, det vill säga så likt det levande som möjligt. Det har visat sig vara viktigt att kunna studera nervcellernas elektriska signaler som är ett mått på stressnivån samtidigt som man mäter hur hemoproteiner samverkar med olika molekyler och proteiner. De elektriska signaleringsegenskaperna hos nervceller eller tunna hjärnsnitt mäts lämpligen genom patch-clamp teknik. Optisk Raman spektroskopi och UV-Vis spektroskopi fungerar väl för att studera haemoproteiner och de första Ramanmätningarna på tunna hjärnskivor visade att det går att skilja åt olika hemoproteiner. För att kunna kontrollera syrehalten krävs det en sluten gastät flödeskammare med möjlighet till patch-clamp där man snabbt kan flöda olika lösningar av varierande syre-, och salthalt. I detta system är patch-clamp pipetten fixerad till en position och cellerna förs till pipetten med hjälp av en optisk pincett som är en beröringsfri optisk manipuleringsmetod där biologiska celler fångas i ett starkt fokuserat laserljus som här förflyttas med hjälp av ett xyz-bord. Vi kommer att presentera de senaste framstegen i utvecklandet av mätsystemet där röda blodceller användes som modell.

First measurements on a combined instrument with a thin fibre optic Raman probe mounted inside a hollow tactile resonance sensor have been performed in ambient light on porcine tissue. The ambient fluorescent light was removed successfully from the spectra. The stiffness and the biomolecular composition of the tissue were analysed.

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.