Particle Size Analysis of Pharmaceutical Powders by Laser Diffraction

Raaka-aineen hiukkaskoko on lääkekehityksessä keskeinen materiaaliparametri. Lääkeaineen partikkelikoko vaikuttaa moneen lääketuotteen tärkeään ominaisuuteen, esimerkiksi lääkkeen biologiseen hyväksikäytettävyyteen. Tässä diplomityössä keskityttiin jauhemaisten lääkeaineiden hiukkaskoon määrittämiseen laserdiffraktiomenetelmällä. Menetelmä perustuu siihen, että partikkeleista sironneen valon intensiteetin sirontakulmajakauma on riippuvainen partikkelien kokojakaumasta. Työn kirjallisuusosassa esiteltiin laserdiffraktiomenetelmän teoriaa. PIDS (Polarization Intensity Differential Scattering) tekniikka, jota voidaan käyttää laserdiffraktion yhteydessä, on myös kuvattu kirjallisuusosassa. Muihin menetelmiin perustuvista analyysimenetelmistä tutustuttiin mikroskopiaan sekä aerodynaamisen lentoajan määrittämiseen perustuvaan menetelmään. Kirjallisuusosassa esiteltiin myös partikkelikoon yleisimpiä esitystapoja. Työn kokeellisen osan tarkoituksena oli kehittää ja validoida laserdiffraktioon perustuva partikkelikoon määritysmenetelmä tietylle lääkeaineelle. Menetelmäkehitys tehtiin käyttäen Beckman Coulter LS 13 320 laserdiffraktoria. Laite mahdollistaa PIDS-tekniikan käytön laserdiffraktiotekniikan ohella. Menetelmäkehitys aloitettiin arvioimalla, että kyseinen lääkeaine soveltuu parhaiten määritettäväksi nesteeseen dispergoituna. Liukoisuuden perusteella väliaineeksi valittiin tällä lääkeaineella kyllästetty vesiliuos. Dispergointiaineen sekä ultraäänihauteen käyttö havaittiin tarpeelliseksi dispergoidessa kyseistä lääkeainetta kylläiseen vesiliuokseen. Lopuksi sekoitusnopeus näytteensyöttöyksikössä säädettiin sopivaksi. Validointivaiheessa kehitetyn menetelmän todettiin soveltuvan hyvin kyseiselle lääkeaineelle ja tulosten todettiin olevan oikeellisia sekä toistettavia. Menetelmä ei myöskään ollut herkkä pienille häiriöille.

Counter-propagating dual-trap optical tweezers based on linear momentum conservation

We present a dual-trap optical tweezers setup which directly measures forces using linear momentum conservation. The setup uses a counter-propagating geometry, which allows momentum measurement on each beam separately. The experimental advantages of this setup include low drift due to all-optical manipulation, and a robust calibration (independent of the features of the trapped object or buffer medium) due to the force measurement method. Although this design does not attain the high-resolution of some co-propagating setups, we show that it can be used to perform different single molecule measurements: fluctuation-based molecular stiffness characterization at different forces and hopping experiments on molecular hairpins. Remarkably, in our setup it is possible to manipulate very short tethers (such as molecular hairpins with short handles) down to the limit where beads are almost in contact. The setup is used to illustrate a novel method for measuring the stiffness of optical traps and tethers on the basis of equilibrium force fluctuations, i.e., without the need of measuring the force vs molecular extension curve. This method is of general interest for dual trap optical tweezers setups and can be extended to setups which do not directly measure forces.

Particle shape and orientation in laser diffraction and static image analysis size distribution analysis of micrometer sized rectangular particles

Laser diffraction (LD) and static image analysis (SIA) of rectangular particles [United States Pharmacopeia, USP30-NF25, General Chapter <776>, Optical Miroscopy.] have been systematically studied. To rule out sample dispersion and particle orientation as the root cause of differences in size distribution profiles, we immobilize powder samples on a glass plate by means of a dry disperser. For a defined region of the glass plate, we measure the diffraction pattern as induced by the dispersed particles, and the 2D dimensions of the individual particles using LD and optical microscopy, respectively. We demonstrate a correlation between LD and SIA, with the scattering intensity of the individual particles as the dominant factor. In theory, the scattering intensity is related to the square of the projected area of both spherical and rectangular particles. In traditional LD the size distribution profile is dominated by the maximum projected area of the particles (A). The diffraction diameters of a rectangular particle with length L and breadth B as measured by the LD instrument approximately correspond to spheres of diameter ØL and ØB respectively. Differences in the scattering intensity between spherical and rectangular particles suggest that the contribution made to the overall LD volume probability distribution by each rectangular particle is proportional to A2/L and A2/B. Accordingly, for rectangular particles the scattering intensity weighted diffraction diameter (SIWDD) explains an overestimation of their shortest dimension and an underestimation of their longest dimension. This study analyzes various samples of particles whose length ranges from approximately 10 to 1000 μm. The correlation we demonstrate between LD and SIA can be used to improve validation of LD methods based on SIA data for a variety of pharmaceutical powders all with a different rectangular particle size and shape.

Assessment of the role of LASER-Doppler in the treatment of port-wine stains in infants.

BACKGROUND: Port-wine stains (PWS) are malformations of capillaries in 0.3% of newborn children. The treatment of choice is by pulsed dye LASER (PDL), and requires several sessions. The efficacy of this treatment is at present evaluated on the basis of clinical inspection and of digital photographs taken throughout the treatment. LASER-Doppler imaging (LDI) is a noninvasive method of imaging the perfusion of the tissues by the microcirculatory system (capillaries). The aim of this paper is to demonstrate that LDI allows a quantitative, numerical evaluation of the efficacy of the PDL treatment of PWS. METHOD: The PDL sessions were organized according to the usual scheme, every other month, from September 1, 2012, to September 30, 2013. LDI imaging was performed at the start and at the conclusion of the PDL treatment, and simultaneously on healthy skin in order to obtain reference values. The results evidenced by LDI were analyzed according to the "Wilcoxon signed-rank" test before and after each session, and in the intervals between the three PDL treatment sessions. RESULTS: Our prospective study is based on 20 new children. On average, the vascularization of the PWS was reduced by 56% after three laser sessions. Compared with healthy skin, initial vascularization of PWS was 62% higher than that of healthy skin at the start of treatment, and 6% higher after three sessions. During the 2 months between two sessions, vascularization of the capillary network increased by 27%. CONCLUSION: This study shows that LDI can demonstrate and measure the efficacy of PDL treatment of PWS in children. The figures obtained when measuring the results by LDI corroborate the clinical assessments and may allow us to refine, and perhaps even modify, our present use of PDL and thus improve the efficacy of the treatment.

Fetal laser therapy: applications in the management of fetal pathologies.

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy.

Deposition and characterization of lines printed through laser-induced forward transfer

The possibility of printing two-dimensional micropatterns of biomolecule solutions is of great interest in many fields of research in biomedicine, from cell-growth and development studies to the investigation of the mechanisms of communication between cells. Although laser-induced forward transfer (LIFT) has been extensively used to print micrometric droplets of biological solutions, the fabrication of complex patterns depends on the feasibility of the technique to print micron-sized lines of aqueous solutions. In this study we investigate such a possibility through the analysis of the influence of droplet spacing of a water and glycerol solution on the morphology of the features printed by LIFT. We prove that it is indeed possible to print long and uniform continuous lines by controlling the overlap between adjacent droplets. We show how, depending on droplet spacing, several printed morphologies are generated, and we offer, in addition, a simple explanation of the observed behavior based on the jetting dynamics characteristic of the LIFT of liquids.

Occlusal and dentofacial characteristics of the deciduous dentition and treatment effects of the eruption guidance appliance in the early mixed dentition

The aim of this investigation was to analyze the dental occlusion in the deciduous dentition, and the effects of orthodontic treatment carried out in the early mixed dentition with the eruption guidance appliance. The deciduous occlusion and craniofacial morphology of 486 children (244 girls and 242 boys) were investigated at the onset of the mixed dentition period (mean age 5.1 years, range 4.0-7.8 years). Treatment in the treatment group and follow-up in the control group were started when the first deciduous incisor was exfoliated (T1) and ended when all permanent incisors and first molars were fully erupted (T2). The mean age of the children was 5.1 years (SD 0.5) at T1 and 8.4 years (SD 0.5) at T2. Treatment was carried out with the eruption guidance appliance. Occlusal changes that took place in 167 children were compared with those of 104 untreated control children. Pre- and post-treatment cephalometric radiographs were taken, and the craniofacial morphology of 115 consecutively treated children was compared with that of 104 control children. The prevalence of malocclusion in the deciduous dentition was 68% or 93% depending on how the cut-off value between the acceptable and non-acceptable occlusal characteristic was defined. The early dentofacial features of children with distal occlusion, large overjet and deepbite differed from those with normal occlusion. However, the skeletal pattern of these three malocclusions showed considerable similarity each being characterized by a retrusive mandible, small maxillo-mandibular difference, convex profile, retrusive lower incisors, and large interincisal angle. In the treatment group, overjet and overbite decreased significantly from T1 to T2. Following treatment, a tooth-to-tooth contact was found in 99% of the treated children but only in 24% of the controls. A Class I molar relationship was observed in 90% of the children in the treatment group, and in 48% in the control group. Good alignment of the incisors was observed in 98% of the treated children, whereas upper crowding was found in 32% and lower crowding in 47% of the controls. A significant difference between the groups was found in the mandibular length, midfacial length and maxillo-mandibular differential. The occlusal correction, brought about by the eruption guidance appliance, was achieved mainly through changes in the dentoalveolar region of the mandible. In addition, the appliance seemed to enhance the growth of the mandible. Treatment in the early mixed dentition using the eruption guidance appliance is an effective method to normalize occlusion and reduce further need of orthodontic treatment. Only few spontaneous corrective changes can be expected without active intervention.

Photomultiplier nonlinear response in time-domain laser-induced luminescence spectroscopy

A new procedure to find the limiting range of the photomultiplier linear response of a low-cost, digital oscilloscope-based time-resolved laser-induced luminescence spectrometer (TRLS), is presented. A systematic investigation on the instrument response function with different signal input terminations, and the relationship between the luminescence intensity reaching the photomultiplier and the measured decay time are described. These investigations establish that setting the maximum intensity of the luminescence signal below 0.3V guarantees, for signal input terminations equal or higher than 99.7 ohm, a linear photomultiplier response.

A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custombuilt optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications.

Superconducting properties and their enhancement in ReBa2Cu3O7-delta (RE = Y and Gd) films prepared by pulsed laser deposition

Due to font problem on the tilte field the titlte of the thesis is corrected here. The title of the thesis is: Superconducting properties and their enhancement in ReBa₂Cu₃O₇-delta (RE = Y and Gd) films prepared by pulsed laser deposition

Product costing model for laser welded hollow core steel panels

The aim of the study was to create an easily upgradable product costing model for laser welded hollow core steel panels to help in pricing decisions. The theory section includes a literature review to identify traditional and modern cost accounting methodologies, which are used by manufacturing companies. The theory section also presents the basics of steel panel structures and their manufacturing methods and manufacturing costs based on previous research. Activity-Based costing turned out to be the most appropriate methodology for the costing model because of wide product variations. Activity analysis and the determination of cost drivers based on observations and interviews were the key steps in the creation of the model. The created model was used to test how panel parameters affect the costs caused by the main manufacturing stages and materials. By comparing cost structures, it was possible to find the panel types that are the most economic and uneconomic to manufacture. A sensitivity analysis proved that the model gives sufficiently reliable cost information to support pricing decisions. More reliable cost information could be achieved by determining the cost drivers more accurately. Alternative methods for manufacturing the cores were compared with the model. The comparison proved that roll forming can be more advantageous and flexible than press brake bending. However, more extensive research showed that roll forming is possible only when the cores are designed to be manufactured by roll forming. Due to that fact, when new panels are designed consideration should be given to the possibility of using roll forming.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Characterisation of Laser Beam and Paper Material Interaction

It is known already from 1970´s that laser beam is suitable for processing paper materials. In this thesis, term paper materials mean all wood-fibre based materials, like dried pulp, copy paper, newspaper, cardboard, corrugated board, tissue paper etc. Accordingly, laser processing in this thesis means all laser treatments resulting material removal, like cutting, partial cutting, marking, creasing, perforation etc. that can be used to process paper materials. Laser technology provides many advantages for processing of paper materials: non-contact method, freedom of processing geometry, reliable technology for non-stop production etc. Especially packaging industry is very promising area for laser processing applications. However, there are only few industrial laser processing applications worldwide even in beginning of 2010´s. One reason for small-scale use of lasers in paper material manufacturing is that there is a shortage of published research and scientific articles. Another problem, restraining the use of laser for processing of paper materials, is colouration of paper material i.e. the yellowish and/or greyish colour of cut edge appearing during cutting or after cutting. These are the main reasons for selecting the topic of this thesis to concern characterization of interaction of laser beam and paper materials. This study was carried out in Laboratory of Laser Processing at Lappeenranta University of Technology (Finland). Laser equipment used in this study was TRUMPF TLF 2700 carbon dioxide laser that produces a beam with wavelength of 10.6 μm with power range of 190-2500 W (laser power on work piece). Study of laser beam and paper material interaction was carried out by treating dried kraft pulp (grammage of 67 g m-2) with different laser power levels, focal plane postion settings and interaction times. Interaction between laser beam and dried kraft pulp was detected with different monitoring devices, i.e. spectrometer, pyrometer and active illumination imaging system. This way it was possible to create an input and output parameter diagram and to study the effects of input and output parameters in this thesis. When interaction phenomena are understood also process development can be carried out and even new innovations developed. Fulfilling the lack of information on interaction phenomena can assist in the way of lasers for wider use of technology in paper making and converting industry. It was concluded in this thesis that interaction of laser beam and paper material has two mechanisms that are dependent on focal plane position range. Assumed interaction mechanism B appears in range of average focal plane position of 3.4 mm and 2.4 mm and assumed interaction mechanism A in range of average focal plane position of 0.4 mm and -0.6 mm both in used experimental set up. Focal plane position 1.4 mm represents midzone of these two mechanisms. Holes during laser beam and paper material interaction are formed gradually: first small hole is formed to interaction area in the centre of laser beam cross-section and after that, as function of interaction time, hole expands, until interaction between laser beam and dried kraft pulp is ended. By the image analysis it can be seen that in beginning of laser beam and dried kraft pulp material interaction small holes off very good quality are formed. It is obvious that black colour and heat affected zone appear as function of interaction time. This reveals that there still are different interaction phases within interaction mechanisms A and B. These interaction phases appear as function of time and also as function of peak intensity of laser beam. Limit peak intensity is the value that divides interaction mechanism A and B from one-phase interaction into dual-phase interaction. So all peak intensity values under limit peak intensity belong to MAOM (interaction mechanism A one-phase mode) or to MBOM (interaction mechanism B onephase mode) and values over that belong to MADM (interaction mechanism A dual-phase mode) or to MBDM (interaction mechanism B dual-phase mode). Decomposition process of cellulose is evolution of hydrocarbons when temperature is between 380- 500°C. This means that long cellulose molecule is split into smaller volatile hydrocarbons in this temperature range. As temperature increases, decomposition process of cellulose molecule changes. In range of 700-900°C, cellulose molecule is mainly decomposed into H2 gas; this is why this range is called evolution of hydrogen. Interaction in this range starts (as in range of MAOM and MBOM), when a small good quality hole is formed. This is due to “direct evaporation” of pulp via decomposition process of evolution of hydrogen. And this can be seen can be seen in spectrometer as high intensity peak of yellow light (in range of 588-589 nm) which refers to temperature of ~1750ºC. Pyrometer does not detect this high intensity peak since it is not able to detect physical phase change from solid kraft pulp to gaseous compounds. As interaction time between laser beam and dried kraft pulp continues, hypothesis is that three auto ignition processes occurs. Auto ignition of substance is the lowest temperature in which it will spontaneously ignite in a normal atmosphere without an external source of ignition, such as a flame or spark. Three auto ignition processes appears in range of MADM and MBDM, namely: 1. temperature of auto ignition of hydrogen atom (H2) is 500ºC, 2. temperature of auto ignition of carbon monoxide molecule (CO) is 609ºC and 3. temperature of auto ignition of carbon atom (C) is 700ºC. These three auto ignition processes leads to formation of plasma plume which has strong emission of radiation in range of visible light. Formation of this plasma plume can be seen as increase of intensity in wavelength range of ~475-652 nm. Pyrometer shows maximum temperature just after this ignition. This plasma plume is assumed to scatter laser beam so that it interacts with larger area of dried kraft pulp than what is actual area of beam cross-section. This assumed scattering reduces also peak intensity. So result shows that assumably scattered light with low peak intensity is interacting with large area of hole edges and due to low peak intensity this interaction happens in low temperature. So interaction between laser beam and dried kraft pulp turns from evolution of hydrogen to evolution of hydrocarbons. This leads to black colour of hole edges.