Raman Spectroscopy and Surface Plasmon Resonance as Photonic Tools for Biopharmaceutical Applications

Biophotonics is an emerging area of scientific research that uses light of photons to probe biological specimens, such as tissues, cells and molecules. The field of biophotonics is broad and considerably multidisciplinary. Therefore the prerequisite for understanding biophotonics is the capability to integrate the fundamental knowledge of the physics of light with perspectives of engineering of devices and instruments used to generate, modify, and manipulate light. Also, the fundamentals of biology and medicine are essential particularly comprehension of the biochemical and cellular phenomena that occur in living systems, and how such phenomena can be scaled up to concern the physiology of organisms, for example humans. Biological pathways and processes differ in the healthy and diseased state, and that is why it is essential to develop understanding of pathophysiology and various states of disease such as cancer, neurodegenerative disease or infectious states. Consequently, solid insights into the functions of medical treatments, including biopharmaceutics, are needed. Raman and surface plasmon resonance (SPR) are both light-based technologies enabling label-free measurements with high sensitivity. The primary aim of this Thesis was to tackle the emerging hardships encountered in the fundamental biopharmaceutical research, clinical settings, or in the pharmaceutical industry by introducing applications and data analysis methods based on the cutting edge Raman and SPR technologies. These techniques represent the biophotonic cornerstones as tools for biopharmaceutical applications throughout this Thesis. The scope of this Thesis was essentially broad. First, small drug molecules were investigated with state-of-the-art time-gated Raman technology, showing that the interfering photoluminescent backgrounds can be effectively suppressed thus improving the acquired Raman data significantly. Additionally, EVs were studied with laser tweezers Raman spectroscopy (LTRS) as larger scale analytes and representatives of a highly interesting topic in the current nanomedical field. When Raman data from several different types of single EVs was examined using sophisticated data analysis, distinct subpopulations were observed, and the differences could be related to the biochemical compositions of the vesicle membranes. For the first time, the study showed the importance of measuring single EVs instead of a pool of vesicles. Multi-parametric SPR (MP-SPR) technology was harnessed to develop applications and data analysis methods for small and larger scale analytes. Hence, a new small drug molecule, spin-labeled fluorene (SLF), was investigated in the context of Alzheimer s disease (AD) particularly its potential to interfere with the detrimental amyloid peptide aggregation processes. The developed bio-functional in vitro platform in combination with rigorous data analysis and computational simulations demonstrated the capabilities of SLF when it was employed in various biomimetic aggregation schemes. Moreover, liposomes were examined with the MP-SPR as larger scale nanomedical particles for the purposes of safe and effective nanocarrier development. The administration of a liposomal nanocarrier into the blood circulation was mimicked in the designed bionanophotonic in vitro schemes. Undiluted serum was made to interact with immobilized model liposomes in dynamic flow conditions. The findings revealed that the variation in surface chemistries of the liposomes plays a role when serum essentially immune system components are interacting with the liposomes. In particular, distinct soft and hard protein coronas were observed and characterized during the interactions. Collectively, the results and findings in this Thesis underline the broad potential of biophotonics for biopharmaceutical applications. The technical improvements in instrumentation, and creativity in the application and data analysis development make the future of biophotonics bright.Biofotoniikka on kasvava tieteenala, jossa valon fotoneja käytetään biologisten kohteiden tutkimiseen. Esimerkkeinä kudokset, solut ja molekyylit. Biofotoniikka tieteenalana on huomattavan poikkitieteellinen. Valon tuottamiseksi ja muokkaamiseksi tarvitaan perustavanlaatuista tietoa fysiikasta sekä teknisiä taitoja laitteiden suunnittelemiseksi. Lisäksi biologian, ja lääketieteen perusteet ovat olennainen osa biofotoniikkaa. Erityisen tärkeää on ymmärrys biofysiikasta ja -kemiasta sekä molekyyli- ja solutason ilmiöistä, jotka tapahtuvat elävissä systeemeissä. Tämän väitöstyön tavoitteena oli kehittää biofotonisia tekniikoita, menetelmiä ja data-analytiikkaa nykyisen biofarmaseuttisen tutkimuksen haasteisiin. Olemassa olevien in vitro menetelmien, eli esimerkiksi koeputkessa tai maljassa tehtävien biologisten mallisysteemien ongelmana on usein se, että tulosten siirrettävyys kliinisiin tutkimuksiin ja lopullisiksi lääkevalmisteiksi ei ole suoraviivaista. Esimerkiksi leima-aineiden, kuten fluoresoivien tai radioaktiivisten molekyylien lisääminen tutkittaviin kohteisiin saattaa muuttaa niiden fysikaalista ja kemiallista käyttäytymistä elävässä ympäristössä. Raman-spektroskopia ja pintaplasmoniresonanssi ovat molemmat valoon perustuvia teknologioita, joilla mittauksia voidaan suorittaa ilman leima-aineita ja korkealla herkkyydellä. Molemmista teknologioista käytettiin kehityksen kärjessä olevia instrumentteja. Ne edustivat tässä työssä biofotonisia tekniikoita, joita täydennettiin perinteisillä tutkimusmetodeilla. Väitöstyössä tutkittiin aluksi pienlääkeaineita kiinteässä olomuodossaan Raman-spektroskopian avulla. Raman-spektroskopialla voidaan mitata erittäin tarkasti tutkittavien molekyylien kemiallinen rakenne. Tavallisesti Raman-tutkimusten ongelmana on kuitenkin voimakas fotoluminesenssi, joka tuottaa häiritsevän taustasignaalin ja haittaa Raman-spektrien tulkintaa. Uudella aika-portti Raman-tekniikalla pystyttiin erottelemaan Raman- ja fotoluminesenssisignaalit tehokkaasti. Tämä mahdollisti vaikeasti mitattavien lääkeaineiden Raman-spektrien mittaamisen ja tarkemman karakterisoinnin. Tutkimusten toisessa vaiheessa mitattiin ensimmäistä kertaa yksittäisiä ekstrasellulaarivesikkeleitä. Ekstrasellulaarivesikkelit ovat solujen tuottamia, kalvorakenteisia nanorakenteita, joiden läpimitta on noin 50 1000 nm. Niiden hyödyntäminen syöpädiagnostiikassa ja nanolääketieteellisinä lääkekantajina on kasvavan kiinnostuksen kohteena, mutta tutkimuksia rajoittaa vesikkeleiden biokemiallinen monimuotoisuus ja pieni koko. Mittaukset suoritettiin toisella uudentyyppisellä Raman-tekniikalla, laser-ansalla. Terveiden solujen ja syöpäsolujen tuottamien vesikkeleiden biokemiallista koostumusta arvioitiin kehitetyn monimuuttuja-analyysin keinoin ja havaittiin, että merkittävimmät erot vesikkeleiden välillä liittyivät niiden pintarakenteiden erilaisuuteen. Saaduilla tuloksilla on merkitystä vesikkeleiden funktioiden ymmärtämisessä ja niiden hyödyntämisessä nanolääketieteellisissä applikaatioissa. Väitöstutkimuksen kahdessa muussa osiossa kehitettiin pintaplasmoniresonanssiin pohjautuvia menetelmiä sekä data-analyysiä niin ikään pienlääkemolekyylien ja nanolääketieteellisten kohteiden tutkimukseen. Käytetty moderni pintaplasmoniresonanssitekniikka mahdollisti perinteisestä poikkeavan, perusteellisemman data-analyysin toteuttamisen. Ensin tarkasteltiin Alzheimerin taudin hoitoon kehitettyä uutta lääkemolekyyliä, jonka oli todettu hidastavan haitallista amyloid-peptidien yhteenliittymistä. Tutkimuksissa kehitetty bio-funktionaalinen in vitro alusta yhdessä tietokonesimulaatioiden kanssa osoitti, että tutkittu molekyyli vähensi selvästi amyloid-aggregaatiota. Analyysillä pystyttiin myös karakterisoimaan molekyylin interaktio-ominaisuuksia. Liposomit edustivat väitöstutkimuksen viimeisessä osuudessa nanolääketieteellisiä partikkeleita, joiden ominaisuuksia tutkittiin pintaplasmoniresonanssin avulla. Tällä hetkellä ainoat ihmiskäyttöön hyväksytyt nanolääkekantajat perustuvat liposomeihin. Kehitetyllä bionanofotonisella in vitro -alustalla matkittiin liposomikantajan annostelua verenkiertoon. Laimentamattoman seerumin annettiin vuorovaikuttaa sensoripinnalle immobilisoitujen liposomien kanssa dynaamisissa virtausolosuhteissa. Tulokset osoittivat, että liposomien pintakemialla on todennäköisesti vahva vaikutus siihen, miten seerumin komponentit, erityisesti immuunijärjestelmä, reagoivat annosteltuun liposomikantajaan. Havainnoilla on potentiaalista merkitystä turvallisten ja tehokkaiden lääkekantajien kehitystyössä. Yhteenvetona voidaan todeta, että biofotoniikkaa voidaan hyödyntää hyvin luovalla tavalla biofarmaseuttisiin applikaatioihin. Väitöstutkimuksen tulokset osoittavat, että kehitetyillä alustoilla ja data-analyysimenetelmillä on mahdollista parantaa nykyistä pienlääkekehitystä sekä nanolääketieteellistä tutkimusta

Cells and Organs on Chip—A Revolutionary Platform for Biomedicine

Lab‐on‐a‐chip (LOC) and microfluidics are important technologies with numerous applications from drug delivery to tissue engineering. LOC integrates fluidic and electronic components on a single chip and becomes very attractive due to the possibility of their state‐of‐art implementation in personalized devices for the point‐of‐care treatments. Microfluidics is the technique that deals with small (10-9 to 10-18 L) amounts of fluids, using channels with dimensions of 10 to 100 μm. These LOC and microfluidics devices enable the development of next‐generation portable and implantable bioelectronics devices. Superior chip‐based technologies are emerging with the advances in microfluidics and motivating various chip‐based methods for rapid low‐cost analysis as compared to traditional laboratory method.An organ‐on‐chip (OOC) is on‐chip cell culture device created with microfabrication techniques and contains continuously perfused chambers inhabited by living cells that simulate tissue‐ and organ‐level physiology. In vitro models of cells, tissues and organ based on LOC devices are a major breakthrough for research in biologic systems and mechanisms. The recapitulations of cellular events in OOC devices provide them an edge over two‐dimensional (2D) and three‐dimensional (3D) cultures and open a gateway for their newer applications in biomedicine such as tissue engineering, drug discovery and disease modeling. In this chapter, the advancement and potential applications of OOC devices are discussed

Non-labelled surface sensitive techniques as platforms for pharmaceutical nanotechnology research

Insufficient delivery of drugs to the target sites like tumors and cells has been a barrier for achieving satisfying therapeutic effects in many diseases. Distribution and exposure of drugs to normal and healthy tissues may enhance the possibility of side effects and toxicity in vivo. Nanoparticle (NP) drug delivery systems have been developed to enable targeting of drugs to target sites and at the same time also reduce or even eliminate the distribution and exposure of drugs to non-targeted sites (normal and healthy tissues). The interactions of ligand attached NPs with specific receptors on the cell surface enable intracellular delivery of drugs. Knowledge of the molecular mechanisms (kinetics and affinity) of specific NP surface interactions is vital for designing and optimizing NPs based targeted drug delivery systems. Biophysical non-labelled surface sensitive detection techniques allow the characterization of the specific NP-cell interactions in vitro at the molecular levels. In this work, surface sensitive non-labelled surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) biosensors were optimized, utilized and further developed as platforms for in vitro characterization and evaluation of the targeting of NP drug delivery systems. A multi-parameter SPR (MP-SPR) prototype was modified, improved and optimized for characterizing molecular surface interactions and phospholipid based thin film properties. The methodologies to extract simultaneously the thickness and the optical properties of thin films were developed by using the multi-wavelength SPR technique. The methodologies were extended to cover the film thickness from few nanometers to micrometers by combining the SPR wavelength and the waveguide mode analysis. These methods were successfully utilized for analyzing LB mono- and multilayers and further for the polyelectrolyte multilayer films. In order to enable the combined use of SPR and QCM techniques for drug and NP interaction studies, these two devices were synchronized to achieve consistent hydrodynamic conditions in the flow channels by computational fluid dynamics (CFD) modelling. The flow channels and the device synchronization were verified by the streptavidin-biotin and liposome-surface interactions. The synchronized SPR and QCM devices were further utilized for the examination of the targeting properties via the streptavidin-biotin liposome interactions under different shear flows. The effect of the flow rate and shear stress on the targeted liposome with the target surface was investigated. The results from SPR and QCM measurements were compared, showing that the binding of the targeted liposome was flow rate and shear stress regulated. According to the SPR measurements, high flow rates improved the binding of liposomes to the target surface. However, the results obtained from the QCM measurements were somehow different. They gave additional information about the liposome binding behavior, indicating deformation or rupture of the bound liposomes at high flow rates and shear stresses. In conclusion, SPR and QCM, the two label free surface sensitive techniques, are excellent platforms for pharmaceutical nanotechnology research. These allow for both the nanoparticle interaction studies and the characterization of nanoscale thin films. Especially, the combined use of the synchronized SPR and QCM techniques forms a powerful platform for the qualitative and quantitative characterization of NP-surface interactions for obtaining in-depth understanding of the targeting behavior of NP drug delivery systems. The results obtained provides the basis for developing new complementary in vitro platforms to traditional cell based in vitro assays for optimizing and screening of NP based targeted drug delivery systems.Lääkeannostelu on keskeinen alue lääketutkimuksessa. Lääkeaineiden riittämätön jakelu kohteeseen estää monien sairauksien kohdalla tyydyttävän terapeuttisen vaikutuksen saavuttamisen. Lääkeaineiden leviäminen ja vaikutus terveisiin kudoksiin saattaa lisätä sivuvaikutuksien ja toksisuuden mahdollisuutta in vivo. On kehitetty nanopartikkelipohjaisia lääkeannostelumenetelmiä, jotta lääkeaineita voitaisiin kohdentaa paremmin ja samalla vähentää tai jopa kokonaan välttää lääkeaineiden leviämistä ja vaikutusta kohdealueen ulkopuolelle. Ligandilla funktionalisoitujen nanopartikkeleiden vuorovaikutus solupinnalla olevien spesifisten reseptorien kanssa mahdollistaa lääkeaineiden kuljettamisen solun sisään. Spesifisten nanopartikkeleiden pintavuorovaikutukset ja niiden molekulaaristen mekanismien tuntemus (kinetiikka ja affiniteetti) ovat keskeisiä kehitettäessä ja optimoitaessa nanopartikkelipohjaisia lääkeannostelumenetelmiä. Biofysikaaliset pintaherkät mittausmenetelmät tarjoavat mahdollisuuden karakterisoida in vitro spesifisiä nanopartikkelin ja solun välisiä vuorovaikutuksia molekyylitasolla ilman leimoja. Pintaherkät ja leimattomat pintaplasmonresonanssi- (SPR) ja kvartsikidemikrovaaka- (QCM) biosensorit optimoitiin ja niitä hyödynnettiin ja kehitettiin edelleen alustoiksi kohdennettujen nanopartikkelipohjaisten lääkeannostelumenetelmien in vitro -karakterisointia ja arviointia varten. Moniparametristä SPR- (MP-SPR) prototyyppilaitetta muokattiin, paranneltiin ja optimoitiin molekulaaristen pintavuorovaikutusten ja fosfolipidipohjaisten ohutkalvojen karakterisointia varten. Moniaallonpituus-SPR-menetelmää hyödyntäen kehitettiin metodologia, jolla voi samanaikaisesti määrittää ohutkalvojen paksuuden ja sen optiset ominaisuudet. Lisäksi tämä metodologia laajennettiin kattamaan kalvojen paksuudet muutamasta nanometristä mikrometreihin yhdistämällä SPR-aallonpituus- ja aaltojohdinanalyysit. SPR- ja QCM-laitteiden hydrodynaamiset ominaisuudet synkronisoitiin virtauslaskentamallinusten (CFD) kautta, mikä mahdollisti SPR- ja QCM-laitteiden yhteiskäytön lääkeaineiden ja nanopartikkeleiden vuorovaikutuksien tutkimiseen. Virtauskanavien ja laitteiden synkronisointi todennettiin tutkimalla biomolekulaarista vuorovaikutusta ja nanopartikkeli-pinta-vuorovaikutusta. Synkronoituja SPR- ja QCM-laitteita hyödynnettiin edelleen kohdennuksen ominaisuuksien tutkimiseen mittaamalla streptavidin-biotinyloitujen liposomien vuorovaikutuksia eri virtausnopeuksilla. Virtausnopeuden ja leikkausjännitteen vaikutus kohdennetun liposomin käyttäytymiseen kohdepinnan kanssa tutkittiin. SPR- ja QCM-mittauksia verrattiin keskenään. Mittaukset osoittivat, että kohdennetun liposomin sitoutumista pintaan säätelivät virtausnopeus ja leikkausjännite. QCM antoi lisätietoa liposomien sitoutumiskäyttäytymisestä ja osoitti, että pinnalle sitoutuneet liposomit muuttivat muotoaan tai hajosivat korkeissa virtaunopeuksissa tai leikkausjänitteissä. Päätelmänä voidaan todeta, että, SPR ja QCM ovat erinomaisia menetelmiä farmaseuttisen nanoteknologian tutkimukseen. Nämä menetelmät mahdollistavat nanopartikkeleiden vuorovaikutuksien tutkimisen sekä ohutkalvojen karakterisoimisen. Synkronoitujen SPR- ja QCM-menetelmien yhteiskäyttö muodostaa tehokkaan alustan kvalitatiiviselle ja kvantitatiiviselle nanopartikkeli-pinta-vuorovaikutuksien karakterisoinnille, joka auttaa paremmin ymmärtämään nanopartikkelipohjaisten lääkeannostelumenetelmien kohdennuskäyttäytymistä. Tulokset tarjoavat perustan uusien täydentävien in vitro -alustojen kehittämiselle perinteisten solupohjaisten in vitro -menetelmien rinnalle nanopartikkelipohjaisten lääkeannostelumenetelmien optimointiin ja seulontaan

Lab-on-a-Chip Fabrication and Application

The necessity of on-site, fast, sensitive, and cheap complex laboratory analysis, associated with the advances in the microfabrication technologies and the microfluidics, made it possible for the creation of the innovative device lab-on-a-chip (LOC), by which we would be able to scale a single or multiple laboratory processes down to a chip format. The present book is dedicated to the LOC devices from two points of view: LOC fabrication and LOC application

Design of Tribologically Enhanced Polymeric Materials for Biomedical Applications

Anytime two surfaces are in normal contact, accompanied by tangential motion, there is potential for deterioration of one or both surfaces. Gradual wear, or the removal of surface material, is typically an undesirable event. Therefore, the need for lubrication arises to minimize the amount of shear stress that develops between opposing surfaces. This reduction in shear stress is characterized by the coefficient of friction (COF). Friction is one of the primary subjects of interest in tribology, the science of the friction and wear of articulating surfaces. A number of fascinating tribological systems can be found in nature. One example which has drawn a considerable interest is articular cartilage. This smooth white tissue lines the articulating surfaces of our joints and sustains a tremendous amount of stress while maintaining smooth joint motion and low COF. The low COF exhibited by articular cartilage is unmatched by any man-made material. The phenomenal tribological properties of this biphasic material are attributed to a combination of a unique boundary lubrication mechanism and its ability to support interstitial fluid pressurization This dissertation details the synthesis and characterization of novel tribologically enhanced polymeric materials which show great potential for several biomedical applications. Design of these material relied on the use of biomimetic tribological mechanisms. The overarching characterization described in this investigation provides valuable insight into the physical and mechanical characteristics of these unique materials

Review on carbon-derived, solid-state, micro and nano sensors for electrochemical sensing applications

The aim of this review is to summarize the most relevant contributions in the development of electrochemical sensors based on carbon materials in the recent years. There have been increasing numbers of reports on the first application of carbon derived materials for the preparation of an electrochemical sensor. These include carbon nanotubes, diamond like carbon films and diamond film-based sensors demonstrating that the particular structure of these carbon material and their unique properties make them a very attractive material for the design of electrochemical biosensors and gas sensors. Carbon nanotubes (CNT) have become one of the most extensively studied nanostructures because of their unique properties. CNT can enhance the electrochemical reactivity of important biomolecules and can promote the electron-transfer reactions of proteins (including those where the redox center is embedded deep within the glycoprotein shell). In addition to enhanced electrochemical reactivity, CNT-modified electrodes have been shown useful to be coated with biomolecules (e.g., nucleic acids) and to alleviate surface fouling effects (such as those involved in the NADH oxidation process). The remarkable sensitivity of CNT conductivity with the surface adsorbates permits the use of CNT as highly sensitive nanoscale sensors. These properties make CNT extremely attractive for a wide range of electrochemical sensors ranging from amperometric enzyme electrodes to DNA hybridization biosensors. Recently, a CNT sensor based fast diagnosis method using non-treated blood assay has been developed for specific detection of hepatitis B virus (HBV) (human liver diseases, such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma caused by hepatitis B virus). The linear detection limits for HBV plasma is in the range 0.5–3.0 μL−1 and for anti- HBVs 0.035–0.242 mg/mL in a 0.1 M NH4H2PO4 electrolyte solution. These detection limits enables early detection of HBV infection in suspected serum samples. Therefore, non-treated blood serum can be directly applied for real-time sensitive detection in medical diagnosis as well as in direct in vivo monitoring. Synthetic diamond has been recognized as an extremely attractive material for both (bio-) chemical sensing and as an interface to biological systems. Synthetic diamond have outstanding electrochemical properties, superior chemical inertness and biocompatibility. Recent advances in the synthesis of highly conducting nanocrystalline-diamond thin films and nano wires have lead to an entirely new class of electrochemical biosensors and bio-inorganic interfaces. In addition, it also combines with development of new chemical approaches to covalently attach biomolecules on the diamond surface also contributed to the advancement of diamond-based biosensors. The feasibility of a capacitive field-effect EDIS (electrolyte-diamond-insulatorsemiconductor) platform for multi-parameter sensing is demonstrated with an O-terminated nanocrystalline-diamond (NCD) film as transducer material for the detection of pH and penicillin concentration. This has also been extended for the label-free electrical monitoring of adsorption and binding of charged macromolecules. One more recent study demonstrated a novel bio-sensing platform, which is introduced by combination of a) geometrically controlled DNA bonding using vertically aligned diamond nano-wires and b) the superior electrochemical sensing properties of diamond as transducer material. Diamond nanowires can be a new approach towards next generation electrochemical gene sensor platforms. This review highlights the advantages of these carbon materials to promote different electron transfer reactions specially those related to biomolecules. Different strategies have been applied for constructing carbon material-based electrochemical sensors, their analytical performance and future prospects are discussed

Marine Skeletal Biopolymers and Proteins, and Their Biomedical Application

This book covers recent trends in all aspects of basic and applied scientific research on marine skeletal proteins and biopolymers (e.g., chitin, collagen), and their derivatives. Some recent innovations of marine proteins have been incorporated in this book that could be potentially applied in scientific and industrial research. Due to their broad array of biological functions in biopolymer- and protein-based drugs, such as anticancer, antimicrobial, bone tissue regeneration, antioxidant, and anti-aging functions, bioactive skeletal proteins and biopolymers have recently attracted a great amount of interest in the pharmaceutical, nutraceutical, and cosmeceutical industries (including anti-aging drugs)

High Precision 3D Printing for Micro to Nano Scale Biomedical and Electronic Devices

Three dimensional printing (3DP), or additive manufacturing, is an exponentially growing process in the fabrication of various technologies with applications in sectors such as electronics, biomedical, pharmaceutical and tissue engineering. Micro and nano scale printing is encouraging the innovation of the aforementioned sectors, due to the ability to control design, material and chemical properties at a highly precise level, which is advantageous in creating a high surface area to volume ratio and altering the overall products’ mechanical and physical properties. In this review, micro/-nano printing technology, mainly related to lithography, inkjet and electrohydrodynamic (EHD) printing and their biomedical and electronic applications will be discussed. The current limitations to micro/-nano printing methods will be examined, covering the difficulty in achieving controlled structures at the miniscule micro and nano scale required for specific applications

A microfabricated microconcentrator for sensors and chromatography

The detection and quantitative measurement of trace components is a challenging task. The key component in such an instrument is the concentration step where the analytes are accumulated before the analysis. In this research, simple and inexpensive processes for the microfabrication of microconcentrator that can be used with sensors and as an injector in GC were developed. Analytes are selectively concentrated in the microconcentrator. Rapid electrical heating of the microconcentrator releases the adsorbed species as a 66 concentration pulse , which serves as an injection for the detection system. The relatively small size of the microconcentrator allows it to be heated and cooled rapidly. The microconcentrator serves the dual purposes of sample concentration and injection. The devices were fabricated on 6-inch silicon substrate using standard photolithographic processes. First, a microheater embedded in silicon wafer was fabricated. The channels were lined with a conductive layer by sputtering metal film through which an electric current could be passed causing Ohmic heating. The preconcentration was done on thin-film polymeric layer deposited in the channel. Rapid heating of the conductive layer caused the desorption pulse to be injected into the sensor/detector. Several channel configurations were fabricated with a width between 50 to 456 μ-m depth between 35 and 350 μ-m and length between 6 and 19 cm. The separation distance between the channels was varied such that the entire microheater fitted in a 1cm 2 area. Due to their small size, the microconcentrators could be fabricated more than 50 at a time on a 6-inch silicon wafer. In the first part of this research, the heating characteristics of the microheaters are studied. Deposition of metals to form a resistive heating element in microchannels was demonstrated. It was found that temperature as high as 360°C could be attained in a ten seconds. The microconcentrator was effective as a concentrator plus injector. It exhibited high signal enhancement and precision

Materials Science and Technology

Materials are important to mankind because of the benefits that can be derived from the manipulation of their properties, for example electrical conductivity, dielectric constant, magnetization, optical transmittance, strength and toughness. Materials science is a broad field and can be considered to be an interdisciplinary area. Included within it are the studies of the structure and properties of any material, the creation of new types of materials, and the manipulation of a material's properties to suit the needs of a specific application. The contributors of the chapters in this book have various areas of expertise. therefore this book is interdisciplinary and is written for readers with backgrounds in physical science. The book consists of fourteen chapters that have been divided into four sections. Section one includes five chapters on advanced materials and processing. Section two includes two chapters on bio-materials which deal with the preparation and modification of new types of bio-materials. Section three consists of three chapters on nanomaterials, specifically the study of carbon nanotubes, nano-machining, and nanoparticles. Section four includes four chapters on optical materials