Layout decomposition for triple patterning lithography

Nowadays the semiconductor industry is continuing to advance the limits of physics as the feature size of the chip keeps shrinking. Products of the 22 nm technology node are already available on the market, and there are many ongoing research studies for the 14/10 nm technology nodes and beyond. Due to the physical limitations, the traditional 193 nm immersion lithography is facing huge challenges in fabricating such tiny features. Several types of next-generation lithography techniques have been discussed for years, such as {\em extreme ultra-violet} (EUV) lithography, {\em E-beam direct write}, and {\em block copolymer directed self-assembly} (DSA). However, the source power for EUV is still an unresolved issue. The low throughput of E-beam makes it impractical for massive productions. DSA is still under calibration in research labs and is not ready for massive industrial deployment. Traditionally features are fabricated under single litho exposure. As feature size becomes smaller and smaller, single exposure is no longer adequate in satisfying the quality requirements. {\em Double patterning lithography} (DPL) utilizes two litho exposures to manufacture features on the same layer. Features are assigned to two masks, with each mask going through a separate litho exposure. With one more mask, the effective pitch is doubled, thus greatly enhancing the printing resolution. Therefore, DPL has been widely recognized as a feasible lithography solution in the sub-22 nm technology node. However, as the technology continues to scale down to 14/10 nm and beyond, DPL begins to show its limitations as it introduces a high number of stitches, which increases the manufacturing cost and potentially leads to functional errors of the circuits. {\em Triple pattering lithography} (TPL) uses three masks to print the features on the same layer, which further enhances the printing resolution. It is a natural extension for DPL with three masks available, and it is one of the most promising solutions for the 14/10 nm technology node and beyond. In this thesis, TPL decomposition for standard-cell-based designs is extensively studied. We proposed a polynomial time triple patterning decomposition algorithm which guarantees finding a TPL decomposition if one exists. For complex designs with stitch candidates, our algorithm is able to find a solution with the optimal number of stitches. For standard-cell-based designs, there are additional coloring constraints where the same type of cell should be fabricated following the same pattern. We proposed an algorithm that is guaranteed to find a solution when one exists. The framework of the algorithm is also extended to pattern-based TPL decompositions, where the cost of a decomposition can be minimized given a library of different patterns. The polynomial time TPL algorithm is further optimized in terms of runtime and memory while keeping the solution quality unaffected. We also studied the TPL aware detailed placement problem, where our approach is guaranteed to find a legal detailed placement satisfying TPL coloring constraints as well as minimizing the {\em half-perimeter wire length} (HPWL). Finally, we studied the problem of performance variations due to mask misalignment in {\em multiple patterning decompositions} (MPL). For advanced technology nodes, process variations (mainly mask misalignment) have significant influences on the quality of fabricated circuits, and often lead to unexpected power/timing degenerations. Mask misalignment would complicate the way of simulating timing closure if engineers do not understand the underlying effects of mask misalignment, which only exists in multiple patterning decompositions. We mathematically proved the worst-case scenarios of coupling capacitance incurred by mask misalignment in MPL decompositions. A graph model is proposed which is guaranteed to compute the tight upper bound on the worst-case coupling capacitance of any MPL decompositions for a given layout

Algorithmic techniques for physical design : macro placement and under-the-cell routing

With the increase of chip component density and new manufacturability constraints imposed by modern technology nodes, the role of algorithms for electronic design automation is key to the successful implementation of integrated circuits. Two of the critical steps in the physical design flows are macro placement and ensuring all design rules are honored after timing closure. This thesis proposes contributions to help in these stages, easing time-consuming manual steps and helping physical design engineers to obtain better layouts in reduced turnaround time. The first contribution is under-the-cell routing, a proposal to systematically connect standard cell components via lateral pins in the lower metal layers. The aim is to reduce congestion in the upper metal layers caused by extra metal and vias, decreasing the number of design rule violations. To allow cells to connect by abutment, a standard cell library is enriched with instances containing lateral pins in a pre-selected sharing track. Algorithms are proposed to maximize the numbers of connections via lateral connection by mapping placed cell instances to layouts with lateral pins, and proposing local placement modifications to increase the opportunities for such connections. Experimental results show a significant decrease in the number of pins, vias, and in number of design rule violations, with negligible impact on wirelength and timing. The second contribution, done in collaboration with eSilicon (a leading ASIC design company), is the creation of HiDaP, a macro placement tool for modern industrial designs. The proposed approach follows a multilevel scheme to floorplan hierarchical blocks, composed of macros and standard cells. By exploiting RTL information available in the netlist, the dataflow affinity between these blocks is modeled and minimized to find a macro placement with good wirelength and timing properties. The approach is further extended to allow additional engineer input, such as preferred macro locations, and also spectral and force methods to guide the floorplanning search. Experimental results show that the layouts generated by HiDaP outperforms those obtained by a state-of-the-art EDA physical design software, with similar wirelength and better timing when compared to manually designed tape-out ready macro placements. Layouts obtained by HiDaP have successfully been brought to near timing closure with one to two rounds of small modifications by physical design engineers. HiDaP has been fully integrated in the design flows of the company and its development remains an ongoing effort.A causa de l'increment de la densitat de components en els xip i les noves restriccions de disseny imposades pels últims nodes de fabricació, el rol de l'algorísmia en l'automatització del disseny electrònic ha esdevingut clau per poder implementar circuits integrats. Dos dels passos crucials en el procés de disseny físic és el placement de macros i assegurar la correcció de les regles de disseny un cop les restriccions de timing del circuit són satisfetes. Aquesta tesi proposa contribucions per ajudar en aquests dos reptes, facilitant laboriosos passos manuals en el procés i ajudant als enginyers de disseny físic a obtenir millors resultats en menys temps. La primera contribució és el routing "under-the-cell", una proposta per connectar cel·les estàndard usant pins laterals en les capes de metall inferior de manera sistemàtica. L'objectiu és reduir la congestió en les capes de metall superior causades per l'ús de metall i vies, i així disminuir el nombre de violacions de regles de disseny. Per permetre la connexió lateral de cel·les, estenem una llibreria de cel·les estàndard amb dissenys que incorporen connexions laterals. També proposem modificacions locals al placement per permetre explotar aquest tipus de connexions més sovint. Els resultats experimentals mostren una reducció significativa en el nombre de pins, vies i nombre de violacions de regles de disseny, amb un impacte negligible en wirelength i timing. La segona contribució, desenvolupada en col·laboració amb eSilicon (una empresa capdavantera en disseny ASIC), és el desenvolupament de HiDaP, una eina de macro placement per a dissenys industrials actuals. La proposta segueix un procés multinivell per fer el floorplan de blocks jeràrquics, formats per macros i cel·les estàndard. Mitjançant la informació RTL disponible en la netlist, l'afinitat de dataflow entre els mòduls es modela i minimitza per trobar macro placements amb bones propietats de wirelength i timing. La proposta també incorpora la possibilitat de rebre input addicional de l'enginyer, com ara suggeriments de les posicions de les macros. Finalment, també usa mètodes espectrals i de forçes per guiar la cerca de floorplans. Els resultats experimentals mostren que els dissenys generats amb HiDaP són millors que els obtinguts per eines comercials capdavanteres de EDA. Els resultats també mostren que els dissenys presentats poden obtenir un wirelength similar i millor timing que macro placements obtinguts manualment, usats per fabricació. Alguns dissenys obtinguts per HiDaP s'han dut fins a timing-closure en una o dues rondes de modificacions incrementals per part d'enginyers de disseny físic. L'eina s'ha integrat en el procés de disseny de eSilicon i el seu desenvolupament continua més enllà de les aportacions a aquesta tesi.Postprint (published version

Algorithmic techniques for physical design : macro placement and under-the-cell routing

With the increase of chip component density and new manufacturability constraints imposed by modern technology nodes, the role of algorithms for electronic design automation is key to the successful implementation of integrated circuits. Two of the critical steps in the physical design flows are macro placement and ensuring all design rules are honored after timing closure. This thesis proposes contributions to help in these stages, easing time-consuming manual steps and helping physical design engineers to obtain better layouts in reduced turnaround time. The first contribution is under-the-cell routing, a proposal to systematically connect standard cell components via lateral pins in the lower metal layers. The aim is to reduce congestion in the upper metal layers caused by extra metal and vias, decreasing the number of design rule violations. To allow cells to connect by abutment, a standard cell library is enriched with instances containing lateral pins in a pre-selected sharing track. Algorithms are proposed to maximize the numbers of connections via lateral connection by mapping placed cell instances to layouts with lateral pins, and proposing local placement modifications to increase the opportunities for such connections. Experimental results show a significant decrease in the number of pins, vias, and in number of design rule violations, with negligible impact on wirelength and timing. The second contribution, done in collaboration with eSilicon (a leading ASIC design company), is the creation of HiDaP, a macro placement tool for modern industrial designs. The proposed approach follows a multilevel scheme to floorplan hierarchical blocks, composed of macros and standard cells. By exploiting RTL information available in the netlist, the dataflow affinity between these blocks is modeled and minimized to find a macro placement with good wirelength and timing properties. The approach is further extended to allow additional engineer input, such as preferred macro locations, and also spectral and force methods to guide the floorplanning search. Experimental results show that the layouts generated by HiDaP outperforms those obtained by a state-of-the-art EDA physical design software, with similar wirelength and better timing when compared to manually designed tape-out ready macro placements. Layouts obtained by HiDaP have successfully been brought to near timing closure with one to two rounds of small modifications by physical design engineers. HiDaP has been fully integrated in the design flows of the company and its development remains an ongoing effort.A causa de l'increment de la densitat de components en els xip i les noves restriccions de disseny imposades pels últims nodes de fabricació, el rol de l'algorísmia en l'automatització del disseny electrònic ha esdevingut clau per poder implementar circuits integrats. Dos dels passos crucials en el procés de disseny físic és el placement de macros i assegurar la correcció de les regles de disseny un cop les restriccions de timing del circuit són satisfetes. Aquesta tesi proposa contribucions per ajudar en aquests dos reptes, facilitant laboriosos passos manuals en el procés i ajudant als enginyers de disseny físic a obtenir millors resultats en menys temps. La primera contribució és el routing "under-the-cell", una proposta per connectar cel·les estàndard usant pins laterals en les capes de metall inferior de manera sistemàtica. L'objectiu és reduir la congestió en les capes de metall superior causades per l'ús de metall i vies, i així disminuir el nombre de violacions de regles de disseny. Per permetre la connexió lateral de cel·les, estenem una llibreria de cel·les estàndard amb dissenys que incorporen connexions laterals. També proposem modificacions locals al placement per permetre explotar aquest tipus de connexions més sovint. Els resultats experimentals mostren una reducció significativa en el nombre de pins, vies i nombre de violacions de regles de disseny, amb un impacte negligible en wirelength i timing. La segona contribució, desenvolupada en col·laboració amb eSilicon (una empresa capdavantera en disseny ASIC), és el desenvolupament de HiDaP, una eina de macro placement per a dissenys industrials actuals. La proposta segueix un procés multinivell per fer el floorplan de blocks jeràrquics, formats per macros i cel·les estàndard. Mitjançant la informació RTL disponible en la netlist, l'afinitat de dataflow entre els mòduls es modela i minimitza per trobar macro placements amb bones propietats de wirelength i timing. La proposta també incorpora la possibilitat de rebre input addicional de l'enginyer, com ara suggeriments de les posicions de les macros. Finalment, també usa mètodes espectrals i de forçes per guiar la cerca de floorplans. Els resultats experimentals mostren que els dissenys generats amb HiDaP són millors que els obtinguts per eines comercials capdavanteres de EDA. Els resultats també mostren que els dissenys presentats poden obtenir un wirelength similar i millor timing que macro placements obtinguts manualment, usats per fabricació. Alguns dissenys obtinguts per HiDaP s'han dut fins a timing-closure en una o dues rondes de modificacions incrementals per part d'enginyers de disseny físic. L'eina s'ha integrat en el procés de disseny de eSilicon i el seu desenvolupament continua més enllà de les aportacions a aquesta tesi

Templated dewetting of thin solid films

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 175-179).The dewetting of solid metal polycrystalline films to form metal nanoparticles occurs by the nucleation and growth of holes in the film. For typical films on flat substrates, this process is not well-controlled and results in nanoparticles with nonuniform spatial and size distributions. Topographic substrates consisting of di-periodic inverted pyramid arrays and mono -periodic v-groove gratings of oxidized silicon were used to modulate the surface curvature of as-deposited polycrystalline gold films and control the dewetting process. The morphology of films dewetted on topographic substrates was found to depend on the both the relative geometry of the substrate and film thickness. Relatively thick films dewetted out of the pits and grooves prior to breaking up into particles while thinner films pinched off to form particles in the pits and grooves. If the pits or grooves were far apart, the pinch off also resulted in particles forming on the mesas between the pits. If the pits or grooves are close together, all the material pinches off into the topography. In the case of the inverted pyramids, this resulted in spatially ordered arrays of nanoparticles with narrow size distributions. A model that explains and predicts the effect of the relative geometry was developed based on competition between curvaturedriven evolution of the film-atmosphere interface and the dewetting of the film-substrate interface. It was also found that particles in both types of topographic substrates are strongly crystallographically oriented both out of the plane of the substrate and in the plane of the substrate despite the lack of an epitaxial relationship with the amorphous template.(cont.) During the solid-state dewetting process, the growth of holes in the film is accompanied by material accumulation along the edge of the hole. Investigation of the dewetting edge at early stages revealed that the accumulation occurs unevenly in individual grains. Electron backscatter diffraction revealed that the unevenness is not due to grain orientation.by Amanda L. Giermann.Ph.D

Creation of Defined Single Cell Resolution Neuronal Circuits on Microelectrode Arrays

The way cell-cell organization of neuronal networks influences activity and facilitates function is not well understood. Microelectrode arrays (MEAs) and advancing cell patterning technologies have enabled access to and control of in vitro neuronal networks spawning much new research in neuroscience and neuroengineering. We propose that small, simple networks of neurons with defined circuitry may serve as valuable research models where every connection can be analyzed, controlled and manipulated. Towards the goal of creating such neuronal networks we have applied microfabricated elastomeric membranes, surface modification and our unique laser cell patterning system to create defined neuronal circuits with single-cell precision on MEAs. Definition of synaptic connectivity was imposed by the 3D physical constraints of polydimethylsiloxane elastomeric membranes. The membranes had 20μm clear-through holes and 2-3μm deep channels which when applied to the surface of the MEA formed microwells to confine neurons to electrodes connected via shallow tunnels to direct neurite outgrowth. Tapering and turning of channels was used to influence neurite polarity. Biocompatibility of the membranes was increased by vacuum baking, oligomer extraction, and autoclaving. Membranes were bound to the MEA by oxygen plasma treatment and heated pressure. The MEA/membrane surface was treated with oxygen plasma, poly-D-lysine and laminin to improve neuron attachment, survival and neurite outgrowth. Prior to cell patterning the outer edge of culture area was seeded with 5x105 cells per cm and incubated for 2 days. Single embryonic day 7 chick forebrain neurons were then patterned into the microwells and onto the electrodes using our laser cell patterning system. Patterned neurons successfully attached to and were confined to the electrodes. Neurites extended through the interconnecting channels and connected with adjacent neurons. These results demonstrate that neuronal circuits can be created with clearly defined circuitry and a one-to-one neuron-electrode ratio. The techniques and processes described here may be used in future research to create defined neuronal circuits to model in vivo circuits and study neuronal network processing

Investigations of Structure / Property Interrelationships of Organic Thin Films Using Scanning Probe Microscopy and Nanolithography

Studies of the surface assembly and molecular organization of organic thin films were studied using scanning probe microscopy (SPM) and scanning probe lithography (SPL). Systems of organic thin films such as n-alkanethiols and pyridyl functionalized porphyrins were characterized at the molecular level, and measurements of the conductive properties of polythiophenes containing in-chain cobaltabisdicarbollides were accomplished. Understanding the self-organization and mechanisms of self-assembly of organic molecules provides fundamental insight for structure/property interrelationships. Investigations of the surface assembly of 5,10-diphenyl-15,20-di-pyridin-4-yl-porphyrin (DPP) on Au(111) were done using SPL methods of nanoshaving and nanografting. Automated computer designs were developed for nanofabrication to provide local characterizations of the thickness of DPP films and nanostructures. Nanolithography was accomplished using DPP films as either matrix self-assembled monolayers (SAMs) or as molecules for nanofabrication. Results presented in this dissertation demonstrate that DPP forms compact layers on Au(111), which can be used for inscribing nanopatterns of n-alkanethiols. Arrays of DPP nanopatterns with precise geometries and alignment were fabricated within n-alkanethiols by nanografting, demonstrating nanoscale lithography with pyridyl porphyrins can be accomplished to produce an upright surface orientation on Au(111) mediated by nitrogen-gold chemisorption. Beyond research investigations, the applicability of atomic force microscopy (AFM) and advancements with automated SPL were applied for teaching undergraduate chemistry laboratories to introduce the fundamentals of surface chemistry and molecular manipulation. New classroom activities were developed for the Chemistry 3493 Physical Chemistry laboratory to give students “hands-on” training with AFM. Undergraduates were trained to prepare nanopatterns of n-alkanethiols using software to control the position, force and speed of the AFM tip for nanolithography experiments. The sensitivity and nanoscale resolution of current sensing AFM was applied for studies of the conductive properties of electropolymerized thin films of polythiophenes with cobaltabisdicarbollide moieties. Images acquired with AFM furnished views of the morphology of different polymers prepared on gold surfaces. Surface maps of the conductivity of electropolymerized films were acquired with AFM current images. These studies provide new insight of the effects of the bound cobaltabisdicarbollide moiety and coordinated metal centers for the electronic properties of the resulting conducting materials

Novel Chemical Approach for the Site Selective Generation of Complex Self-Assembled Virus Derivatives

Main goal is to develop a method allowing an efficient and site-selective immobilization of Tobacco mosaic virus (TMV)-RNA on oxidic and polymeric surfaces using a bottom-up self-assembly strategy. Two new chemical approaches are introduced as linkers for DNA-ligands: Aldehyde converted alkoxysilane and in-house synthesized isothiocyanate (ITC) alkoxysilane. Substrates were characterized by X-ray photon spectroscopy (XPS), atomic force microscopy (AFM), contact angle (CA) and optical microscopy

Study of substrate modulation and bioreceptor anchoring for the development of high performance microarrays

Tesis por compendio[EN] The present PhD thesis is focused on the study of new approaches able to improve the performance of microarrays. Aspects such as the nature of the surfaces and the probes, functionalization of the substrates, probe printing, immobilization and target detection were considered in the fabrication process. Within all these features, modulation of the surface behavior and probe anchoring were the most challenging aspects, as the interface is key for the immobilization of the receptors and the later detection, which will determine the performance of the final device. In this work, two microarray types have been developed, one for oligonucleotides and another one for antibodies. Then, a characterization of the reached achievements is done. All the routes have in common the use of light to catalyze the attachment of bioreceptors on the surface substrates, employing click-chemistry reactions. In the first chapter, the state of the art of microarray technology is overviewed, with special focus in the main aspects of microarray design. In the second chapter, the goals for this PhD thesis are settled. These general objectives are addressed in the following experimental chapters. In the third chapter, the effect of hydrophobicity and probe multi-point attachment on the microarray performance are studied. Thus, modulation of glass slide surfaces with alkenyl and alkynyl motifs for the anchoring of mono and multithiolated oligonucleotide probes by thiol-ene and thiol-yne photocoupling reactions, respectively, was accomplished. Surfaces modified with the most hydrophobic silane (alkynyl), or anchoring polythiolated probes, revealed better performances. These microarray systems were applied to the discrimination of SNPs and to detect bacterial genome PCR products. In the fourth chapter, a rational design for the preparation of microarrays of antibodies, is done. The immobilization approach displays the oriented anchoring of thiol-bearing antibody fragments to alkenylated glass slides by thiol-ene photocoupling reaction. Multiplexed detection of cardiac biomarkers is demonstrated. The designed microarray shows higher recognition capacity in comparison to whole antibody microarrays. In the fifth chapter, improvement of a novel methodology for the anchoring of thiolated oligonucleotides has been developed. Due to the interest on modifying highly hydrophobic surfaces, a new photoinduced reaction is set up. Thanks to the features of the named "fluor-thiol photocoupling reaction", immobilization of thiolated probes to surfaces containing C-F bonds in a fast, easy and biocompatible with aqueous media way, was achieved. Hydrophobicity of the surfaces was controlled to get successful hybridizations. Because of the high hydrophobicity of the surfaces, a huge confinement of the probes is accomplished, which allows the approximation of the analytes only where the probe is linked, keeping a high repulsion in the remaining surface. The perfluorinated glass slides improved the immobilization densities and detection capacity, regarding to the alkenylated and alkynylated surfaces, and allowed the discrimination of SNPs and detection of bacterial PCR products, as well. In the sixth chapter, other surfaces different than glass are explored. Thus, polyvinylidene fluoride membranes were employed as substrates for the development of oligonucleotide microarrays. Therefore, a fast, easy and mild functionalization process by UV irradiation and organosilane chemistry, was developed. Then, alkenyl functionalized and non-functionalized membranes were applied to microarray technology by covalent anchoring through thiol-ene and fluor-thiol photocoupling reactions, respectively. Promising results were obtained with both surfaces.[ES] La presente tesis tesis doctoral se centra en el estudio de nuevas aproximaciones capaces de mejorar el rendimiento de los microarrays. Aspectos como la naturaleza de las superficies y las sondas, la funcionalización de los sustratos, la impresión, la inmovilización y la detección de las sondas se consideraron en el proceso de fabricación. Dentro de todas estas características, la modulación de la superficie y el anclaje de la sonda fueron los aspectos más desafiantes, ya que la interfaz es clave para la inmovilización de los receptores y la posterior detección, lo que determinará el rendimiento del dispositivo final. En este trabajo, se han desarrollado dos tipos de microarrays, uno para oligonucleótidos y otro para anticuerpos. Luego, se ha realizado una caracterización de los logros alcanzados. Todas las rutas tienen en común el uso de la luz para catalizar la unión de los biorreceptores en los sustratos de la superficie, empleando reacciones de la química clic. En el primer capítulo, se facilita una visión general del estado del arte de la tecnología de microarrays con un enfoque especial en los aspectos principales del diseño de microarrays. En el segundo capítulo, se establecen los objetivos de esta tesis doctoral. Estos objetivos generales se abordan en los siguientes capítulos experimentales. En el tercer capítulo, se estudia el efecto de la hidrofobia y el uso de sondas con múltiples puntos de unión, en el rendimiento del microarray. De este modo, se llevó a cabo la modulación de superficies vidrio con grupos alquenilo y alquinilo para el anclaje de sondas de oligonucleótidos mono y multitioladas mediante las reacciones de foto anclaje del tiol-eno y tiol-ino, respectivamente. Las superficies modificadas con el silano más hidrofóbico (alquinilo) y las sondas politioladas ancladas, revelaron mejores rendimientos. Estos sistemas de microarrays se aplicaron a la discriminación de SNPs y a la detección de productos de PCR de bacterias. En el cuarto capítulo, se realiza un diseño racional para la preparación de microarrays de anticuerpos. El enfoque de inmovilización muestra el anclaje orientado de los fragmentos de anticuerpos que contienen tiol sobre superficies de vidrio alqueniladas mediante reacción de foto anclaje del tiol-eno. De esta forma, se demuestra la detección multiplexada de biomarcadores cardíacos. El microarray diseñado muestra una mayor capacidad de reconocimiento en comparación con los microarrays de anticuerpos completos. En el quinto capítulo, se ha desarrollado una nueva metodología para mejorar el anclaje de oligonucleótidos tiolados. Dado el interés en modificar superficies altamente hidrófobas, se establece una nueva reacción fotoinducida. Gracias a las características de la llamada "reacción de fotoacoplamiento de fluor-tiol", se logró la inmovilización de sondas tioladas a superficies que contienen enlaces C-F de una manera rápida, fácil y biocompatible con medios acuosos. La hidrofobicidad de las superficies se controló para obtener hibridaciones exitosas. Debido a la alta hidrofobicidad de las superficies, se logra un gran confinamiento de las sondas, lo que permite la aproximación de los analitos solo donde está unida la sonda, manteniendo una alta repulsión en la superficie restante. Las superficies de vidrio perfluoradas mejoraron las densidades de inmovilización y la capacidad de detección, con respecto a las superficies alqueniladas y alquiniladas, y también, permitieron la discriminación de SNPs y la detección de productos de PCR bacterianos. En el sexto capítulo, se exploran otras superficies diferentes al vidrio. Por lo tanto, membranas de fluoruro de polivinilideno se emplearon como sustratos para el desarrollo de microarrays de oligonucleótidos. Para ello, se desarrolló un proceso de funcionalización rápido, fácil y suave, mediante el empleo de irradiación UV y la química de los organosilanos.[CA] La present tesi doctoral es centra en l'estudi de noves aproximacions capaces de millorar el rendiment dels microarrays. Aspectes com ara la naturalesa de les superfícies i les sondes, la funcionalització dels substrats, la impressió, la immobilització i la detecció de les sondes es van considerar en el procés de fabricació. Dins de totes aquestes característiques, la modulació de la superfície i l'ancoratge de la sonda van ser els aspectes més desafiadors, ja que la interfície és clau per a la immobilització dels receptors i la posterior detecció, la qual cosa determinarà el rendiment del dispositiu final. En aquest treball, s'han desenvolupat dos tipus de microarrays, un per a oligonucleòtids i un altre per a anticossos. Després, s'ha realitzat una caracterització dels resultats aconseguits. Totes les rutes tenen en comú l'ús de la llum per a catalitzar la unió dels biorreceptores en els substrats de la superfície, emprant reaccions de la química clic. En el primer capítol, es facilita una visió general de l'estat de l'art de la tecnologia de microarrays amb un enfocament especial en els aspectes principals del disseny de microarrays. En el segon capítol, s'estableixen els objectius d'aquesta tesi doctoral. Aquests objectius generals s'aborden en els següents capítols experimentals. En el tercer capítol, s'estudia l'efecte de la hidrofòbia i l'ús de sondes amb múltiples punts d'unió, en el rendiment del microarray. D'aquesta manera, es va dur a terme la modulació de superfícies de vidre amb grups alquenil i alquinil per a l'ancoratge de sondes de oligonucleòtids mono i multitiolades mitjançant les reaccions de foto ancoratge del tiol-doble enllaç i tiol-triple enllaç, respectivament. Les superfícies modificades amb el silà més hidrofòbic (alquinil) i les sondes politiolades ancorades, van revelar els millors rendiments. Aquests sistemes de microarrays es van aplicar a la discriminació de SNPs i a la detecció de productes de PCR de bacteris. En el quart capítol, es realitza un disseny racional per a la preparació de microarrays d'anticossos. L'enfocament d'immobilització mostra l'ancoratge orientat dels fragments d'anticossos que contenen el grup tiol sobre superfícies de vidre alquenilades mitjançant reacció de foto ancoratge del tiol-doble enllaç. D'aquesta forma, es demostra la detecció multiplexada de biomarcadors cardíacs. El microarray dissenyat mostra una major capacitat de reconeixement en comparació amb els microarrays d'anticossos complets. En el cinqué capítol, s'ha desenvolupat una nova metodologia per a millorar l'ancoratge de oligonucleòtids tiolats. Donat l'interés de modificar superfícies altament hidròfobes, s'estableix una nova reacció fotoinduïda. Gràcies a les característiques de l'anomenada "reacció de fotoacoplament de fluor-tiol", es va aconseguir la immobilització de sondes tioladas a superfícies que contenen enllaços C-F d'una manera ràpida, fàcil i biocompatible amb medis aquosos. La hidrofobicitat de les superfícies es va controlar per a obtindre bones hibridacions reeixides. A causa de l'alta hidrofobicidad de les superfícies, s'aconsegueix un gran confinament de les sondes, la qual cosa permet l'aproximació dels anàlits únicament on està unida la sonda i manté una alta repulsió en la superfície restant. Les superfícies de vidre perfluorades van millorar les densitats d'immobilització i la capacitat de detecció, respecte a les superfícies alquenilades i alquinilades, i també van permetre la discriminació de SNPs i la detecció de productes de PCR bacterians. En el sisé capítol, s'exploren altres superfícies diferents al vidre. Per tant, membranes de fluorur de polivinilidé es van emprar com a substrats per al desenvolupament de microarrays d'oligonucleòtids. Per a això, es va desenvolupar un procés de funcionalització ràpid, fàcil i suau, mitjançant l'ús d'irradiació UV i la química dels organosilanAgradecer al Ministerio de Economía y Competitividad de España, por su programa de becas doctorales FPIJiménez Meneses, P. (2020). Study of substrate modulation and bioreceptor anchoring for the development of high performance microarrays [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/137993TESISCompendi