An instrument is being developed at the Department of Biomedical Engineering; Research and Development (MT-FoU), at the University Hospital of Umeå with the aim to detect prostate cancer ex vivo. Using a combination of tactile resonance technology and Raman spectroscopy the instrument is intended to be used in the operating room during radical prostatectomy to identify positive surgical margins. The hypothesis was that the length of the piezoelectric element used in the tactile resonance sensor affects the sensor's sensitivity and reproducibility when measuring the stiffness of soft tissue, and that there might be an optimal impression depth to measure at. The specific aim of this study was to evaluate two piezoelectric elements, of different lengths, by the sensitivity and reproducibility of the measurements they performed. Measurements were performed on five silicone samples of different stiffness, during a 2 mm impression. The standard deviation of the stiffness parameters, the R2 of the linear regression used to determine the stiffness parameter, and the depth at the which the most linear relationship between impression force and frequency shift was found were studied using linear mixed-effects models to identify any significant differences between the elements. The long element had a significantly higher R2 of 0.98 compared to 0.93 for the short element, and a higher measurement depth of 0.47 mm compared to 0.37 mm for the short element. No difference between the elements were found on accuracy as measured by standard deviation of the stiffness parameter. It was concluded that this was not enough to claim that one element was better than the other. / Ett instrument utvecklas på avdelningen för Medicinsk teknik, forskning och utveckling, vid Norrlands universitetssjukhus med målet att detektera prostatacancer ex vivo. Instrumentet kombinerar taktil resonansteknologi med Ramanspektroskopi och är tänkt att användas i operationssalen under radikal prostatektomi för att identifiera positiv kirurgisk marginal. Hypotesen var att längden av det piezoleketriska element som används i den taktila resonanssensorn påverkar sensorns känslighet och reproducerbarhet vid mätning av styvhet av mjukvävnad, och att det kan finnas ett optimalt intryckningsdjup att mäta på. Målet med denna studie var att utvärdera två piezoelektriska element, av olika längd, utifrån känsligheten och reproducerbarheten av mätningarna de utförde. Mätningarna gjordes på fem silikonsprover av olika styvhet, under 2 mm intryckning. Standardavvikelsen av styvhetsparametern, R2 av den linjära regression som användes för att bestämma styvhetsparametern, samt det intryckningsdjup på vilket det mest linjära förhållandet mellan intryckningskraft och frekvensskift hittades, studerade med så kallade linear mixed-effects modeller för att identifiera signifikanta skillnader mellan elementen. Det långa elementet hade ett signifikant högre R2 på 0.98 jämfört med det korta elementets 0.93, och ett högre mätdjup på 0.47 mm jämfört med det korta elementets 0.37 mm. Ingen skillnad mellan elementens standardavvikelser av styvhetsparametern hittades. Slutsatsen drogs att resultatet inte var nog för att påstå att det ena elementet är bättre än det andra.

The scientific studies associated with material engineering and device miniaturization are the core concepts for future technology innovation. The exploring and tailoring of material properties of amorphous magnetic microwires, recently, have revealed remarkable high sensitive magnetic field sensitivity down to the picoTesla regime at room temperature. This superior magnetometer is highly promising for active sensing and real-time monitoring building block for modern industrial devices and healthcare applications. The low-field, high sensitivity regime of the GMI response over a wide frequency range (1 MHz - 1 GHz) in the Co-rich melt-extracted microwires was optimized through novel Joule annealing methods (single- and multi-step current annealing techniques). Optimization of current value through multi-step current annealing (MSA) from 20 mA to 100 mA for 10 minutes is the key to improving the GMI ratio, and its field sensitivity up to 760% and 925%/Oe at f ≈ 20 MHz. The respective GMI ratio and field sensitivity are 1.75 times and 17.92 times higher than those of the as-prepared counterpart. The employment of the MSA technique successfully enhances the surface domain structures of the Co-rich microwires. This alternative tailoring method is suitable for improving the GMI sensitivity for a small field detection. The high sensitive response of the GMI to a weak magnetic field is highly promising for biomedical sensing applications. Real-time monitoring of position, motion, and rotation of a non-stationary object is crucial for product packaging, conveying, tracking, and safety compliance in industrial applications. The effectiveness of current sensing technology is limited by sensing distance and messy environments. A new class of high-frequency GMI-based sensor was designed and fabricated using the optimal Co-rich microwire. The impedance spectrum from the optimal sensing element showed a high GMI ratio and high field sensitivity response at low magnetic fields. The GMI sensor based longitudinal effect was found to be more sensitive than the commercially available Gaussmeters. The practical utility of the high sensitivity of the miniaturized sensor at weak magnetic fields for far-off distance monitoring of position, speed and gear rotating was demonstrated. This GMI-based sensor is highly promising for real-time position detection, oscillatory motion monitoring, and predictive failure of a rotating gear for industrial applications. Monitoring the rate of respiration and its pattern is crucial to assessing an individual’s health or progression of an illness, creating a pressing need for fast, reliable and cost-effective monitors. A new sensor based on a magnetic coil, which is made of Co-rich melt-extracted microwire for the detection of small magnetic fields was fabricated. The 3 mm diameter coil is wound from a Co-rich magnetic microwire. Unlike some typical solenoids, the MMC is sensitive to small magnetic fields due to a significant change in impedance attributed to the high-frequency giant magneto-impedance (GMI) effect. An application of the MMC sensor for the detection of a position-varying source of a small magnetic field (~0.01 – 10 Oe) in real-time bio-mechanical movement monitoring in human was demonstrated. This newly developed MMC magneto-LC resonance technology is highly promising for active respiratory motion monitoring, eye movement detection and other biomedical field sensing applications.

<p>Prostate cancer is the most common type of cancer in men in Europe and the USA. Some prostate tumours are regarded as stiffer than the surrounding normal tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. The methods presently used to detect prostate cancer are inexact, and new techniques are needed. In this licentiate thesis resonance sensor technology, with its ability to measure tissue stiffness, was applied to normal and cancerous prostate tissue.</p><p>A piezoelectric transducer element in a feedback system can be set to vibrate at its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various pathophysiological conditions.</p><p>An impression-controlled resonance sensor system was used to quantify stiffness in human prostate tissue in vitro using a combination of frequency change and force measurements. Measurements on prostate tissue showed statistically significant (p < 0.001) and reproducible differences between normal healthy tissue and tumour tissue when using a multivariate parameter analysis. Measured stiffness varied in both the normal tissue and tumour tissue group. One source of variation was assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces, different levels of dehydration of the prostates, and actual differences between patients.</p><p>The prostate specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5–1.7 mm, the maximum coefficient of determination was R2 ≥ 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed.</p><p>It is concluded that prostate cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differentiate from cancer. Furthermore, the results of this study indicated that the resonance sensor could be used to detect stiffness variations in human prostate tissue in vitro, and especially due to prostate cancer. This is promising for the development of a future diagnostic tool for prostate cancer.</p>

Prostate cancer is the most common type of cancer in men in Europe and the USA. Some prostate tumours are regarded as stiffer than the surrounding normal tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. The methods presently used to detect prostate cancer are inexact, and new techniques are needed. In this licentiate thesis resonance sensor technology, with its ability to measure tissue stiffness, was applied to normal and cancerous prostate tissue. A piezoelectric transducer element in a feedback system can be set to vibrate at its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various pathophysiological conditions. An impression-controlled resonance sensor system was used to quantify stiffness in human prostate tissue in vitro using a combination of frequency change and force measurements. Measurements on prostate tissue showed statistically significant (p &lt; 0.001) and reproducible differences between normal healthy tissue and tumour tissue when using a multivariate parameter analysis. Measured stiffness varied in both the normal tissue and tumour tissue group. One source of variation was assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces, different levels of dehydration of the prostates, and actual differences between patients. The prostate specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5–1.7 mm, the maximum coefficient of determination was R2 ≥ 0.60 (p &lt; 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. It is concluded that prostate cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differentiate from cancer. Furthermore, the results of this study indicated that the resonance sensor could be used to detect stiffness variations in human prostate tissue in vitro, and especially due to prostate cancer. This is promising for the development of a future diagnostic tool for prostate cancer.

Prostate cancer is the most frequent type of cancer in men in Europe and the USA. The methods presently used to detect and diagnose prostate cancer are inexact, and new techniques are needed. Prostate tumours can be regarded as harder than the surrounding normal healthy glandular tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. In this dissertation the approach was to evaluate tactile resonance sensor technology and its ability to measure mechanical properties and to detect cancer in human prostate tissue. The tactile resonance sensor is based on a piezoelectric transducer element vibrating at its resonance frequency through a feedback circuit. A change in the resonance frequency is observed when the sensor contacts an object. This feature has been utilized to measure tissue stiffness variations due to various pathophysiological conditions. An impression-controlled tactile resonance sensor system was first used to quantify stiffness and evaluate performance on silicone. Then the sensor system was used on fresh human prostate tissue in vitro to measure stiffness using a combination of frequency change and force measurements. Significant differences in measured stiffness between malignant and healthy normal tissue were found, but there were large variations within the groups. Some of the variability was explained by prostate tissue histology using a tissue stiffness model. The tissue content was quantified at four depths in the tissue specimens with a microscope-image-based morphometrical method involving a circular grid. Numerical weights were assigned to the tissue data from the four depths, and the weighted tissue proportions were related to the measured stiffness through a linear model which was solved with a least-squares method. An increase in the proportion of prostate stones, stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Stroma and cancer had the greatest effect and accounted for 90 % of the measured stiffness (45% and 45%, respectively). The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. A sensing depth was extrapolated from the numerical weights for the measurements performed at different impression depths. Horizontal surface tissue variations were studied by altering the circular grid size relative to the contact area between the sensor tip and the tissue. The results indicated that the sensing area was greater than the contact area. The sensor registered spatial tissue variations. Tissue density-related variations, as measured by the frequency change, were weakly significant or non-significant. The measured force registered elastic-related tissue variations, to which stroma and cancer were the most important variables. A theoretical material-dependent linear relation was found between frequency change and force from theoretical models of frequency change and force. Tactile resonance sensor measurements on prostate tissue verified this at small impression depths. From this model, a physical interpretation was given to the parameters used to describe stiffness. These results indicate that tactile resonance sensor technology is promising for assessing soft tissue mechanical properties and especially for prostate tissue stiffness measurement with the goal of detecting prostate cancer. However, further studies and development of the sensor design must be performed to determine the full potential of the method and its diagnostic power. Preferably, measurements of tissue mechanical properties should be used in combination with other methods, such as optical methods, to increase the diagnostic power.

A novel localized surface plasmon resonance (LSPR) sensor that differentiates between background refractive index changes and surface-binding of a target analyte (e.g. a target molecule, protein, or bacterium) is presented. Standard, single channel LSPR sensors cannot differentiate these two effects as their design allows only one mode to be coupled. This novel technique uses two surface plasmon modes to simultaneously measure surface binding and solution refractive index changes. This increases the sensitivity of the sensor. Different channels or modes can be created in sensors with the introduction of gold nanospheres or gold nanorods that act as receptor mechanisms. Once immobilization was achieved on gold nanospheres, the technique was optimized to achieve the same immobilization for gold nanorods to get the expected dual mode spectrum. Intricate fabrication methods are illustrated with using chemically terminated self assembled monolayers. Then the fabrication process advances from chemically silanized nanoparticles, on to specific and systematic patterns generated with the use of Electron Beam Lithography. Comparisons are made within the different methods used, and guidelines are set to create possible room for improvement. Some methods implemented failed, but there was a lot to learn from these unsuccessful outcomes. Finally, the applications of the dual mode sensor are introduced, and current venues where the sensors can be used in chemical and biological settings are discussed.