The goal of this project was to write a program to plot populations of white blood cell types in three dimensions and reduce the information from four dimensions to three in order to make it possible to plot. The dimension reduction should be done with as little loss of information as possible. PCA, principal component analysis, was used to perform the dimension reduction. A program for this was written in MATLAB. The program that builds the plot of the populations was written in c# using Visual Studios. The visualization was made in Unity. It was possible to rotate and zoom into the plot to get a better view. The project was given by Boule Medical AB as a part of the development of a new product. Boule Medical AB only had 2D plots and requested a 3D plot in their new product. The program was handed over to Boule Medical AB for future development.

Electrical bioimpedance spectroscopy is one way to study the electrical properties of biological matter. Different applications of electrical bioimpedance measurements have already been used in both research and clinical scenarios i.e. impedance plethysmography, total body water contents, etc. The electrical properties of tissue reflect the electrical characteristics of the constituent elements of the tissue and depend on its structure. Thus study of the electrical properties not only makes it possible to differentiate among tissues but also to determine the tissue condition. During hypoxia/ischemia the cell activates a certain chain of mechanisms of cellular adaptation in response to the insult. A consequence of these response mechanisms is that the biochemical composition of the cellular environment is altered and the cells swell (cellular edema). These alterations affect the electrical properties of tissue and the changes can be observed through measurement of the electrical bioimpedance of the affected tissue. Based on these ideas, this research work studies the effects of hypoxia/ischemia on the brain electrical impedance. The aim is to obtain the fundamental knowledge that may lead to the development of useful clinical tools for cerebral monitoring based on electrical bioimpedance spectroscopy. / QC 20120217 / Brain damage, Detection and localization of cell swelling

Tests have been performed to determine whether electromagnetic shielding of fine wires for electrophysiological sensing is a possible way to reduce the external noise in recording of nervous signals. By shielding the wires with a layer of silver, forming a coaxial cable, a reduction of the received power on the lead of 11.8-33 dBm was shown over the 10 – 10 000 Hz range when the test wire was subject to an electromagnetic field from an injection cable.  When putting the performance on the interval 50-100 Hz aside the same performance was measured to 25-33 dBm lower received power, which can be explained by 50 Hz noise from the electrical grid interfering with the measurements. However, when the shield was not grounded or grounded through a resistor worse performance was shown. The difference in received power between the unshielded and shielded configuration without grounding the shield was close to 0 dBm. Following this, the type of shielding investigated in this project has the potential to substantially shield thin wires from external interference under the condition that sufficient grounding is provided.

Infectious diseases pose a serious threat to global health. Molecular diagnostics provide solutions for effective control and prevention of infections, however suffers from expensive laboratory equipment, and infrastructure to be fully implemented at point of care (POC), especially at low-resource settings. Lab-on-a-chip that aims to integrate complex biochemical analyses into automated systems is promising for POC analysis. A major challenge is the integration of a complete molecular diagnostic assay, generally translating into complex microfluidics, with the requirement of low fabrication cost. This thesis explores the use of flexible electronics, plastic foils and roll-to-roll manufacturing to enable low-cost microfluidic systems, for molecular diagnostic assays especially targeted towards infectious diseases. Many biochemical assays rely on heat; hence a first aspect in this thesis is the integration of a microheater into microfluidics. In a first project a system for SNP-genotyping is presented using solid phase melting curve analysis to discriminate mutations at a single base resolution. Starting with a glass based concept (paper I) which is further developed to a foil based system (paper II), detection of the polymorphism in the neuropeptide Y associated with increased risk of type II diabetes is demonstrated as a proof of principle. Further development and optimization of the microheater concept has enabled roll-to-roll manufacturing compatibility and multiplexing of targets (paper III). A bacterial sub-typing and multiresistance detection in clinical Staphylococcus Aureus samples is demonstrated for applications in infectious diseases diagnostics. Finally, the microheater concept is further developed to enable μPCR (paper IV). Detection of genomic HIV-1 is demonstrated and a portable detection setup based on an LED light source and low cost CMOS camera for detection was developed. A second aspect of this thesis is integration of light sources and optical detection (paper V-VI). A multilayer system integrating an electroluminescent light source, reactive sensor dyes and organic semiconductor transistor for detection is demonstrated. The system could be used for amine detection in gases (paper V). System was made further roll-to-roll compatible. The system uses an external LED light source and a photodetector processed in only one screen printing- and one dispensing step (paper VI). As a proof of principle, absorbance based DNA hybridization was detected. Collectively, roll-to-roll manufacturing compatible “lab on foil” systems have the potential to improve our ability to diagnose at POC especially at resource-limited settings. / <p>QC 20170426</p>

Rapporten behandlar utvecklingen och konstruktionen av ett laparoskopiskt blodkärlsidentifierande instrument. Identifiering sker med hjälp av fotopletysmografi. Fotopletysmografi betyder ungefär "detektion av volymförändrings med hjälp av ljus". Laparoskopi kan översättas med titthålskirurgi. Laparoskopioperationer sker med små runda instrument som förs in i kroppen. Rapporten diskuterar olika probmodeller, det vill säga hur sensorn skall konstrueras för att erhålla en bra mätsignal. Konkurrerande tekniker och framtida applikationer redovisas på flera ställen i rapporten. Vid mätningar på blodmodell studerades och analyserades signalkvaliten. Till slut skall tilläggas att proben fungerade tillfredsställande. Proben kunde detektera pulsationer i blodmodellen.

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.

This work is a comparison of a well-established and a novel, "green" and efficient technique to separate peptides of pharmaceutical interest. An attempt is made to derive the chromatographic retention behaviour from these techniques to a number of property descriptors derived from the linear sequence of amino acids. A set of therapeutic peptides were carefully chosen to be experimentally evaluated using in silico-based descriptor calculations. A principle component analysis was performed to assess the distribution of calculated descriptors for including peptides with variable properties. A diluent optimization study was also included to find the optimal diluent for peptides with minimal diluent effects and peak splitting phenomena. The results showed that the solvents tert-butanol and methanol performed best between 20-30 and 50 volumetric percent water as additive in SFC and HPLC, respectively. These diluents were then used for the peptides within the set to evaluate the retention and selectivity in HPLC and SFC. SFC performed well in terms of resolving power. Inparticular, SFC was able to separate Leuprolide and Triptorelin while HPLC was not. A comparison was also made in between the two stationary phases CN and XT, where a global selectivity was shown to be higher for CN. This work does also assess a novel method for determining solubility of analytes in supercritical fluid. The method was evaluated using the pharmaceutical compounds caffeine and aspirin and then used to determine solubility of Leu-Enkephalin in 20% (v/v%) methanol. The solubility of caffeine was determined to be 0.45 mg ml-1 in pure SF-CO2 under 140 bar pressure and 3.9 mg ml-1 for aspirin in 2.4% methanol. Both values correlated well with measurements from four acknowledged papers within this field. Leu-Enkephalin was found to have a solubility of 1.90 mg ml-1 using a solvent corresponding to the initial phase condition of the gradient used for peptide analysis in SFC. Further experimental work is required before the method can be implemented as a useful tool in preparative chromatography, however the results presented here show the compatibility of assessing biomolecules in both pure SF-CO2 and mixed with modifier. The possibility to determine solubility with additional modifier infers an important step of including and evaluating these compounds creating a solid support to subsequent large scale separation.

In this master thesis methods for increasing temporal resolution when reconstructing radially sampled MRI data have been developed and evaluated. This has been done in two steps; first the order in which data is sampled in k-space has been optimized, and second; temporal filters have been developed in order to utilize the high sampling density in central regions of k-space as a result of the polar sampling geometry to increase temporal resolution while maintaining image quality.By properly designing the temporal filters the temporal resolution is increased by a factor 3–20 depending on other variables such as imageresolution and the size of the time varying areas in the image. The results are obtained from simulated raw data and subsequent reconstruction. The next step should be to acquire and reconstruct raw data to confirm the results. / This Master thesis work were performed at Dept. Radiation Physis, Linköping University, but examined at Dept. Radiation Physics, Umeå University

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.

Malignant gliomas grow infiltrative in the brain and can therefore not be completely removed by neurosurgical means. However, for an optimized oncological treatment it has proven useful to resect as much as possible of tumor. The identification of the tumor in the marginal zone is difficult but crucial. Studies have shown that visualization of the specific enhancement of 5-aminolevulinic acid(5-ALA) in the tumor can help to maximize the resection. The Department of Biomedical Engineering, Linköping University, has developed an optical hand-held probe (HHP) to identify tumor tissue with a high sensitivity by means of fluorescence spectroscopy. The technical design and the optical properties of the probe were gradually developed in a standard neurosurgical setting during resection of malignant gliomas. The device could easily be implemented in the operating room, meeting all requirements in terms of sterile handling and without interference of any kind with other equipment. The integration of the device in a navigation system and its use in combination with a blue light surgical microscope were simple. Measurements in 27 operations during resection of malignant gliomas were compared to results from biopsies from the same tumor locations. The equipment was tested as a stand-alone device (n = 180), integrated in a navigation system or in combination with the blue light microscope (n = 190). A ratiocal culated from the measurements enabled objective and comparable values for different tissue types, in correspondence with the findings from the histopathological examinations and in accordance with the navigation system as well as with the surgical microscope.The marginal zone was explored and tumor fluorescence could be identified beyond the fluorescence as seen through the microscope. A higher sensitivity of the HHP was confirmed; the specificity was lower. The combined use of the HHP with a navigation system and with asurgical microscope was beneficial. / Maligna hjärntumörer växer infiltrerande i hjärnan och kan därförinte helt avlägsnas genom kirurgiska operationer. För en optimerad behandling har det emellertid visat sig vara av värde att avlägsna såmycket som möjligt av tumörvävnaden. Identifiering av tumören i gränszonen är mycket svårt, men avgörande. Studier har visat att visualisering av den specifika laddningen av 5-aminolevulinsyra (5-ALA) i tumören kan bidra till att maximera resektionen. Institutionen för Medicinsk Teknik (IMT) på Linköpings universitet,har utvecklat en liten handhållen optisk prob (HHP) för att identifiera tumörvävnad med hög känslighet med hjälp avfluorescens-spektroskopi. Den tekniska konstruktionen och de optiska egenskaperna hos proben utvecklades stegvis genom testning i flera neurokirurgiska operationer för resektion av maligna gliom. Utrustningen uppfyllde alla krav när det gällde steril hantering i operationssalen och kunde användas utan störningar av något slag med annan operationsutrustning. Integreringen i ett navigerings-system och användningen i kombination med ett kirurgiskt mikroskop för fluorescens-styrd kirurgi var oproblematiska. Mätningar under 27 operationer vid resektion av maligna gliom jämfördes med resultat från biopsier från samma tumörtagningsställen. Utrustningen testades såväl som en fristående enhet (n = 180) och som integrerad i ett navigationssystem eller i kombination med mikroskopet (n =190). En särskild kvot beräknad ur mätningarna möjliggjorde objektiva och jämförbara värden för olika vävnader, i överensstämmelse med resultaten från de vävnadspatologiska undersökningarna och i överensstämmelse med navigationssystemet såväl som med det kirurgiska mikroskopet. Tumörernas gränszon undersöktes och tumörfluorescens kunde identifieras bortom fluorescensen som mikroskopet visade. En högre känslighet hos HHP bekräftades; specificiteten var lägre. Den kombinerade användningen av HHP med ett navigationssystem och med ett kirurgiskt mikroskop visade sig vara fördelaktig.