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Antimicrobial resistance is considered by many prominent researcher and scientist as a profound global health crisis that us humans must face in the next decade. It is threatening the effectiveness of these once-reliable weapons against bacterial infections and leaving us susceptible to pathogenic agents. The indiscriminate overprescription of antibiotic in healthcare and animal husbandry, has led to an increased emergence of “super bugs”— a resistant strain of bacteria that were once susceptible to antibiotic—. The escalating creation of those resistant bacteria has been coupled with a proliferation of research papers that seek to explain the working mechanism of antibiotics and their efficacy on the bacterial pathogens, however these efforts often fall short of explaining the impact that antibiotics has on the bacterial metabolism. This project utilizes an established technology, specifically silicone nano-wire ion-selective field-effect transistor in an innovative approach to discern alteration in the metabolic pathways induced by various antibiotics. The methodology involves measuring extracellular acidity of the tested culture and converting it to an electrical signal to extract valuable information about the metabolic process of the bacteria, and how is altered in the presence of antibiotics. Empirical observations pertaining bacteriostatic antibiotics suggests comprehensive suppression of metabolic pathways, encompassing the efflux transition from acetyl-CoA to acetate, resulting an elevated pH level in cultures treated with bacteriostatic agents relative to their wild-type counterparts. Our experimental data also indicates a shift in bacterial metabolic and physiological responses to bactericidal antibiotic-induced stress which include an increased respiration rate, and a heightened activity of the TCA cycle in the test group with bactericidal antibiotics, causing acetate uptake from the medium and decelerating the acidification of the treated culture compar

Antimicrobial resistance is considered by many prominent researcher and scientist as a profound global health crisis that us humans must face in the next decade. It is threatening the effectiveness of these once-reliable weapons against bacterial infections and leaving us susceptible to pathogenic agents. The indiscriminate overprescription of antibiotic in healthcare and animal husbandry, has led to an increased emergence of “super bugs”— a resistant strain of bacteria that were once susceptible to antibiotic—. The escalating creation of those resistant bacteria has been coupled with a proliferation of research papers that seek to explain the working mechanism of antibiotics and their efficacy on the bacterial pathogens, however these efforts often fall short of explaining the impact that antibiotics has on the bacterial metabolism. This project utilizes an established technology, specifically silicone nano-wire ion-selective field-effect transistor in an innovative approach to discern alteration in the metabolic pathways induced by various antibiotics. The methodology involves measuring extracellular acidity of the tested culture and converting it to an electrical signal to extract valuable information about the metabolic process of the bacteria, and how is altered in the presence of antibiotics. Empirical observations pertaining bacteriostatic antibiotics suggests comprehensive suppression of metabolic pathways, encompassing the efflux transition from acetyl-CoA to acetate, resulting an elevated pH level in cultures treated with bacteriostatic agents relative to their wild-type counterparts. Our experimental data also indicates a shift in bacterial metabolic and physiological responses to bactericidal antibiotic-induced stress which include an increased respiration rate, and a heightened activity of the TCA cycle in the test group with bactericidal antibiotics, causing acetate uptake from the medium and decelerating the acidification of the treated culture compar

My doctoral research aims at defining the literary characteristics of the concept isfet (the various aspects of chaos) as it is developed in the textual sources of ancient Egypt during the third and second milleniums B.C. First and foremost, this dissertation deals with the analysis of the literary texts called « pessismistic » in which the concept isfet is predominant. These will next be compared to other textual sources which evoke situations of unrest so as to collate the literary means implemented by the Egyptians to describe their conception of chaos. Egyptologists call « pessimistic » the literary texts of ancient Egypt which describe the chaotic state of the Egyptian world deprived of maât : the Admonitions of Ipuwer, Prophecy of Neferti, the Text of Khakheperreseneb, the Dialogue of a Man with his Ba, the Eloquent Peasant. According to conventional wisdom, these texts could refer to the political and social crisis which characterised the First Intermediary Period. However, this specific literary genre should be reconsidered insofar as the implementation of the concept isfet at the heart of each text examined may be the result of distinct motivations. In order to establish the latter, a theme-based and formal analysis will be applied. My research will next focus on the other Egyptian texts in which the concept isfet is developed. It will compare the conception and the representation therein of chaos with a view to determining the intertextual dialogues established with the literary texts examined. This methodological approach is relevent insofar as it makes it possible to detect the interactions between the Egyptian texts and therefore apprehend their meaning. Finally, the literary analysis will be lead in parallel with the establishing of a list of terms relating to chaos and a detailed study of the lexicon, the expressions and the phraseology used., Ma recherche doctorale a pour objectif de définir les caractéristiques littéraires du concept d’isfet (aspects divers du chaos), tel qu’il est développé dans les sources textuelles de l’Égypte ancienne des IIIe et IIe millénaires av. J.-C. Cette thèse porte d’abord et prioritairement sur l’analyse des textes littéraires dits « pessimistes », dans lesquels le concept d’isfet occupe une place prépondérante. Elle les compare ensuite à d’autres sources textuelles qui évoquent des situations de troubles, en vue de confronter les moyens littéraires mis en œuvre par les Égyptiens pour décrire leur conception du chaos. Les égyptologues désignent sous l’appellation de « pessimistes » cinq textes littéraires de l’Égypte ancienne qui décrivent l’état chaotique du monde égyptien privé de la maât : les Admonitions d’Ipou-our, la Prophétie de Néferty, la Complainte de Khâkhéperrê-séneb, le Dialogue d’un homme avec son ba et le Paysan Éloquent. Selon l’opinion généralement admise, ces textes évoqueraient la crise politique et sociale ayant marqué la Première Période intermédiaire. Cependant, il convient de reconsidérer leur appartenance à un genre littéraire défini comme « pessimiste », dans la mesure où la mise en œuvre du concept d’isfet au sein de chaque texte étudié peut résulter de motivations spécifiques. En vue d'établir celles-ci, une méthode d’analyse thématique et formelle sera proposée. Ma recherche s’intéresse ensuite aux autres textes égyptiens, dans lesquels le concept d’isfet est développé : elle compare leur conception et leur représentation du chaos, en vue de déterminer les dialogues intertextuels établis avec les textes littéraires étudiés. Cette approche méthodologique est pertinente, dans la mesure où elle permet de relever les interactions entre les textes égyptiens et d’en comprendre le sens. Enfin, l’analyse littéraire est menée en parallèle au relevé de la terminologie relative au chaos, avec un examen approfondi du lexique, des expressions et de la phrasé, (LALE - Langues et lettres) -- UCL, 2021

An integrated sensor chip with silicon nanowire ion-sensitive field-effect transistors for simultaneous and selective detection of both molecular and elemental ions in a single sample solution is demonstrated. The sensing selectivity is realized by functionalizing the sensor surface with tailor-made mixed-matrix membranes (MMM) incorporated with specific ionophores for the target ions. A biomimetic container molecule, named metal-organic supercontainer (MOSC), is selected as the ionophore for detection of methylene blue (MB+), a molecular ion, while a commercially available Na-ionophore is used for Na+, an elemental ion. The sensors show a near-Nernstian response with 56.4 ± 1.8 mV/dec down to a concentration limit of ∌1 ΌM for MB+ and 57.9 ± 0.7 mV/dec down to ∌60 ΌM for Na+, both with excellent reproducibility. Extensive control experiments on the MB+ sensor lead to identification of the critical role of the MOSC molecules in achieving a stable and reproducible potentiometric response. Moreover, the MB+-specific sensor shows remarkable selectivity against common interfering elemental ions in physiological samples, e.g., H+, Na+, and K+. Although the Na+-specific sensor is currently characterized by insufficient immunity to the interference by MB+, the root cause is identified and remedies generally applicable for hydrophobic molecular ions are discussed. River water experiments are also conducted to prove the efficacy of our sensors., Xi Chen and Qitao Hu contributed equally to this work

Silicon nanowires (SiNW) are in the spotlight for a few years in the research community as a good candidate for biosensing applications. This is attributed to their small dimensions in nanometer scale that offers high sensitivity, label-free detection and at the same time utilizing small amount of sample. While the recent research has concentrated predominantly on utilizing single or multiple SiNW for biosensing applications, very few attempts have been made to integrate SiNW with complementary-metal-oxide- semiconductor (CMOS) integration to arrive at a complete lab-on-chip (LOC) sensor. Further, the manufacturing methods reported thus far in the production of SiNW for biosensing applications have not fully exploited both the front-end-of-line (FEOL) as well as back-end-of-line (BEOL) methods in CMOS integration. Neither does the research community address CMOS integration based methods to realize multi and specific target detection that are important attributes for an ideal LOC biosensor. Integration of SiNW with CMOS circuitry will facilitate real time detection of the output signal and in addition provide a compact small sized sensor that is fully portable operating at high speed. In order to avail the benefits of CMOS circuits and develop a large scale production friendly LOC sensor, the scheme of SiNW fabrication has to facilitate either the FEOL or BEOL CMOS integration schemes. This thesis work is focused on revealing a novel FEOL as well as BEOL scheme for integration of SiNW with CMOS circuitry. The major part of the FEOL research work is concentrated on developing a high volume SiNW manufacturing method that is suitable for industrial production. Likewise, in the BEOL scheme, predominant focus was to develop a wafer scale scheme to integrate network of nanowires (nanonets) with CMOS circuitry to manufacture a monolithic 3D above-IC LOC biosensor. In the FEOL scheme, the SiNWs are fabricated using a revised pattern transfer technique called sidewall transf, Kiselnanotrådar har studerats de senaste åren för biosensortillämpningar på grund av deras dimensioner i nanometer skalan som potentiellt möjliggör hög känslighet, etikettfri detektering samt en liten provmängd. Forskningen har varit fokuserad främst på användandet av enskilda eller ett flertal parallella kiselnanotrådar för biosensor tillämpningar, men lite försök har gjorts att integrera kiselnanotrådar med komplementär CMOS teknologi för att erhålla en komplett ”lab-on-chip” (LOC) sensor. Dessutom har tillverkningsmetoderna för kiselnanotrådar som hittills använts för biosensortillämpningar inte fullt utnyttjat möjligheterna som finns med integration i processflödet där transistorn tillverkas (front-end of-line, FEOL) eller i processflödet där metall ledare tillverkas för att koppla ihop transistorerna sker (back-end-of-line, BEOL). Integration av kiselnanotrådar med CMOS kretsar kommer att underlätta realtidsdetektering av sensorns utsignal och också möjliggöra en kompakt sensor som är bärbar. För att utnyttja fördelarna med CMOS kretsar och utveckla en produktionsvänlig LOC sensor så är det fördelaktigt om kiselnanotrådar kan integreras och produceras på samma chip som CMOS kretsarna. Den här avhandlingen fokuserar på nya metoder att integrera kiselnanotrådar i CMOS teknologins FEOL och BEOL processflöden. Ett huvudmål har varit att utveckla en metod att tillverka kiselnanotrådar i stor skala i FEOL med konventionell utrustning för CMOS tillverkning samt att i BEOL utveckla en process för att tillverka en biosensor med ett nätverk av kiselnanotrådar på hela kiselskivor efter metalliseringen. I FEOL flödet har kiselnanotrådar tillverkats med en utvecklad mönsterteknik, kallad ”sidewall transfer” litografi, som utnyttjar konventionella material i CMOS tillverkning. Användandet optisk litografi och selektiva etstekniker möjligör kontroll av linjebredden hos de tillverkade kiselnanotrådarna. Ett fabrikationsflöde för att tillverka CMOS-kretsar med TiN gate elektrod, QC 20181001

Antigen-based sensing is recognized as a rapid and sensitive analysis among bioresearch groups. The potential of “on-site” analysis in such devices has been accompanied by some problems. Fabrication of silicon compatible and highly sensitive biosensors has been the center of excessive research within the past few years. In this paper, we report fabrication of two types of sensitive liquid oxide semiconductor (LOS) biosensors using nanostructures. These devices have been manufactured and characterized as immunosensors. These two types of sensors have been produced using different platforms for immobilization of proteins; one based on a functionalized silicon dioxide surface by 3-aminopropyltriethoxysilane (APTES) and another on the basis of using 50-nm amine-modified polystyrene nanobeads. The polystyrene platform not only benefits from its nanosize and high surface to volume ratio but also does not need any new protocol than what is already used for traditional immunosensing system. These sensors measure the change of threshold voltage of the semiconductor inversion inside the capacitor due to the bonding of antibodies to the linked peptides on the surface. Measurements showed that the sensitivity of 50-nm polystyrene-based sensor is much more than the oxide-based one. The nanobeads were then chosen to cover the gate of the ISFET for the amplified sensing. The ISFET devices were biased in a subthreshold region to demonstrate the maximum sensitivity to the accumulated charge on the gate. Repeatable results after different stress tests were obtained, which proves the suitability and reliability of the polystyrene nanobead platform for this application. Finally, a calibration curve has been derived that can be used for real sample measurements. The detection limit of 1.0152 μg/ml was calculated for the fabricated sensor. [Figure not available: see fulltext.]., Export Date: 22 October 2018; Article; Correspondence Address: Kolahdouz, M.; School of Electrical and Computer Engineering, University of TehranIran; email: kolahdouz@ut.ac.ir. QC 20181113

Silicon nanowires (SiNW) are in the spotlight for a few years in the research community as a good candidate for biosensing applications. This is attributed to their small dimensions in nanometer scale that offers high sensitivity, label-free detection and at the same time utilizing small amount of sample. While the recent research has concentrated predominantly on utilizing single or multiple SiNW for biosensing applications, very few attempts have been made to integrate SiNW with complementary-metal-oxide- semiconductor (CMOS) integration to arrive at a complete lab-on-chip (LOC) sensor. Further, the manufacturing methods reported thus far in the production of SiNW for biosensing applications have not fully exploited both the front-end-of-line (FEOL) as well as back-end-of-line (BEOL) methods in CMOS integration. Neither does the research community address CMOS integration based methods to realize multi and specific target detection that are important attributes for an ideal LOC biosensor. Integration of SiNW with CMOS circuitry will facilitate real time detection of the output signal and in addition provide a compact small sized sensor that is fully portable operating at high speed. In order to avail the benefits of CMOS circuits and develop a large scale production friendly LOC sensor, the scheme of SiNW fabrication has to facilitate either the FEOL or BEOL CMOS integration schemes. This thesis work is focused on revealing a novel FEOL as well as BEOL scheme for integration of SiNW with CMOS circuitry. The major part of the FEOL research work is concentrated on developing a high volume SiNW manufacturing method that is suitable for industrial production. Likewise, in the BEOL scheme, predominant focus was to develop a wafer scale scheme to integrate network of nanowires (nanonets) with CMOS circuitry to manufacture a monolithic 3D above-IC LOC biosensor. In the FEOL scheme, the SiNWs are fabricated using a revised pattern transfer technique called sidewall transf, Kiselnanotrådar har studerats de senaste åren för biosensortillämpningar på grund av deras dimensioner i nanometer skalan som potentiellt möjliggör hög känslighet, etikettfri detektering samt en liten provmängd. Forskningen har varit fokuserad främst på användandet av enskilda eller ett flertal parallella kiselnanotrådar för biosensor tillämpningar, men lite försök har gjorts att integrera kiselnanotrådar med komplementär CMOS teknologi för att erhålla en komplett ”lab-on-chip” (LOC) sensor. Dessutom har tillverkningsmetoderna för kiselnanotrådar som hittills använts för biosensortillämpningar inte fullt utnyttjat möjligheterna som finns med integration i processflödet där transistorn tillverkas (front-end of-line, FEOL) eller i processflödet där metall ledare tillverkas för att koppla ihop transistorerna sker (back-end-of-line, BEOL). Integration av kiselnanotrådar med CMOS kretsar kommer att underlätta realtidsdetektering av sensorns utsignal och också möjliggöra en kompakt sensor som är bärbar. För att utnyttja fördelarna med CMOS kretsar och utveckla en produktionsvänlig LOC sensor så är det fördelaktigt om kiselnanotrådar kan integreras och produceras på samma chip som CMOS kretsarna. Den här avhandlingen fokuserar på nya metoder att integrera kiselnanotrådar i CMOS teknologins FEOL och BEOL processflöden. Ett huvudmål har varit att utveckla en metod att tillverka kiselnanotrådar i stor skala i FEOL med konventionell utrustning för CMOS tillverkning samt att i BEOL utveckla en process för att tillverka en biosensor med ett nätverk av kiselnanotrådar på hela kiselskivor efter metalliseringen. I FEOL flödet har kiselnanotrådar tillverkats med en utvecklad mönsterteknik, kallad ”sidewall transfer” litografi, som utnyttjar konventionella material i CMOS tillverkning. Användandet optisk litografi och selektiva etstekniker möjligör kontroll av linjebredden hos de tillverkade kiselnanotrådarna. Ett fabrikationsflöde för att tillverka CMOS-kretsar med TiN gate elektrod, QC 20181001

Silicon nanowires (SiNW) are in the spotlight for a few years in the research community as a good candidate for biosensing applications. This is attributed to their small dimensions in nanometer scale that offers high sensitivity, label-free detection and at the same time utilizing small amount of sample. While the recent research has concentrated predominantly on utilizing single or multiple SiNW for biosensing applications, very few attempts have been made to integrate SiNW with complementary-metal-oxide- semiconductor (CMOS) integration to arrive at a complete lab-on-chip (LOC) sensor. Further, the manufacturing methods reported thus far in the production of SiNW for biosensing applications have not fully exploited both the front-end-of-line (FEOL) as well as back-end-of-line (BEOL) methods in CMOS integration. Neither does the research community address CMOS integration based methods to realize multi and specific target detection that are important attributes for an ideal LOC biosensor. Integration of SiNW with CMOS circuitry will facilitate real time detection of the output signal and in addition provide a compact small sized sensor that is fully portable operating at high speed. In order to avail the benefits of CMOS circuits and develop a large scale production friendly LOC sensor, the scheme of SiNW fabrication has to facilitate either the FEOL or BEOL CMOS integration schemes. This thesis work is focused on revealing a novel FEOL as well as BEOL scheme for integration of SiNW with CMOS circuitry. The major part of the FEOL research work is concentrated on developing a high volume SiNW manufacturing method that is suitable for industrial production. Likewise, in the BEOL scheme, predominant focus was to develop a wafer scale scheme to integrate network of nanowires (nanonets) with CMOS circuitry to manufacture a monolithic 3D above-IC LOC biosensor. In the FEOL scheme, the SiNWs are fabricated using a revised pattern transfer technique called sidewall transf, Kiselnanotrådar har studerats de senaste åren för biosensortillämpningar på grund av deras dimensioner i nanometer skalan som potentiellt möjliggör hög känslighet, etikettfri detektering samt en liten provmängd. Forskningen har varit fokuserad främst på användandet av enskilda eller ett flertal parallella kiselnanotrådar för biosensor tillämpningar, men lite försök har gjorts att integrera kiselnanotrådar med komplementär CMOS teknologi för att erhålla en komplett ”lab-on-chip” (LOC) sensor. Dessutom har tillverkningsmetoderna för kiselnanotrådar som hittills använts för biosensortillämpningar inte fullt utnyttjat möjligheterna som finns med integration i processflödet där transistorn tillverkas (front-end of-line, FEOL) eller i processflödet där metall ledare tillverkas för att koppla ihop transistorerna sker (back-end-of-line, BEOL). Integration av kiselnanotrådar med CMOS kretsar kommer att underlätta realtidsdetektering av sensorns utsignal och också möjliggöra en kompakt sensor som är bärbar. För att utnyttja fördelarna med CMOS kretsar och utveckla en produktionsvänlig LOC sensor så är det fördelaktigt om kiselnanotrådar kan integreras och produceras på samma chip som CMOS kretsarna. Den här avhandlingen fokuserar på nya metoder att integrera kiselnanotrådar i CMOS teknologins FEOL och BEOL processflöden. Ett huvudmål har varit att utveckla en metod att tillverka kiselnanotrådar i stor skala i FEOL med konventionell utrustning för CMOS tillverkning samt att i BEOL utveckla en process för att tillverka en biosensor med ett nätverk av kiselnanotrådar på hela kiselskivor efter metalliseringen. I FEOL flödet har kiselnanotrådar tillverkats med en utvecklad mönsterteknik, kallad ”sidewall transfer” litografi, som utnyttjar konventionella material i CMOS tillverkning. Användandet optisk litografi och selektiva etstekniker möjligör kontroll av linjebredden hos de tillverkade kiselnanotrådarna. Ett fabrikationsflöde för att tillverka CMOS-kretsar med TiN gate elektrod, QC 20181001

Silicon nanowires (SiNW) are in the spotlight for a few years in the research community as a good candidate for biosensing applications. This is attributed to their small dimensions in nanometer scale that offers high sensitivity, label-free detection and at the same time utilizing small amount of sample. While the recent research has concentrated predominantly on utilizing single or multiple SiNW for biosensing applications, very few attempts have been made to integrate SiNW with complementary-metal-oxide- semiconductor (CMOS) integration to arrive at a complete lab-on-chip (LOC) sensor. Further, the manufacturing methods reported thus far in the production of SiNW for biosensing applications have not fully exploited both the front-end-of-line (FEOL) as well as back-end-of-line (BEOL) methods in CMOS integration. Neither does the research community address CMOS integration based methods to realize multi and specific target detection that are important attributes for an ideal LOC biosensor. Integration of SiNW with CMOS circuitry will facilitate real time detection of the output signal and in addition provide a compact small sized sensor that is fully portable operating at high speed. In order to avail the benefits of CMOS circuits and develop a large scale production friendly LOC sensor, the scheme of SiNW fabrication has to facilitate either the FEOL or BEOL CMOS integration schemes. This thesis work is focused on revealing a novel FEOL as well as BEOL scheme for integration of SiNW with CMOS circuitry. The major part of the FEOL research work is concentrated on developing a high volume SiNW manufacturing method that is suitable for industrial production. Likewise, in the BEOL scheme, predominant focus was to develop a wafer scale scheme to integrate network of nanowires (nanonets) with CMOS circuitry to manufacture a monolithic 3D above-IC LOC biosensor. In the FEOL scheme, the SiNWs are fabricated using a revised pattern transfer technique called sidewall transf, Kiselnanotrådar har studerats de senaste åren för biosensortillämpningar på grund av deras dimensioner i nanometer skalan som potentiellt möjliggör hög känslighet, etikettfri detektering samt en liten provmängd. Forskningen har varit fokuserad främst på användandet av enskilda eller ett flertal parallella kiselnanotrådar för biosensor tillämpningar, men lite försök har gjorts att integrera kiselnanotrådar med komplementär CMOS teknologi för att erhålla en komplett ”lab-on-chip” (LOC) sensor. Dessutom har tillverkningsmetoderna för kiselnanotrådar som hittills använts för biosensortillämpningar inte fullt utnyttjat möjligheterna som finns med integration i processflödet där transistorn tillverkas (front-end of-line, FEOL) eller i processflödet där metall ledare tillverkas för att koppla ihop transistorerna sker (back-end-of-line, BEOL). Integration av kiselnanotrådar med CMOS kretsar kommer att underlätta realtidsdetektering av sensorns utsignal och också möjliggöra en kompakt sensor som är bärbar. För att utnyttja fördelarna med CMOS kretsar och utveckla en produktionsvänlig LOC sensor så är det fördelaktigt om kiselnanotrådar kan integreras och produceras på samma chip som CMOS kretsarna. Den här avhandlingen fokuserar på nya metoder att integrera kiselnanotrådar i CMOS teknologins FEOL och BEOL processflöden. Ett huvudmål har varit att utveckla en metod att tillverka kiselnanotrådar i stor skala i FEOL med konventionell utrustning för CMOS tillverkning samt att i BEOL utveckla en process för att tillverka en biosensor med ett nätverk av kiselnanotrådar på hela kiselskivor efter metalliseringen. I FEOL flödet har kiselnanotrådar tillverkats med en utvecklad mönsterteknik, kallad ”sidewall transfer” litografi, som utnyttjar konventionella material i CMOS tillverkning. Användandet optisk litografi och selektiva etstekniker möjligör kontroll av linjebredden hos de tillverkade kiselnanotrådarna. Ett fabrikationsflöde för att tillverka CMOS-kretsar med TiN gate elektrod, QC 20181001

Silicon nanowires (SiNW) are in the spotlight for a few years in the research community as a good candidate for biosensing applications. This is attributed to their small dimensions in nanometer scale that offers high sensitivity, label-free detection and at the same time utilizing small amount of sample. While the recent research has concentrated predominantly on utilizing single or multiple SiNW for biosensing applications, very few attempts have been made to integrate SiNW with complementary-metal-oxide- semiconductor (CMOS) integration to arrive at a complete lab-on-chip (LOC) sensor. Further, the manufacturing methods reported thus far in the production of SiNW for biosensing applications have not fully exploited both the front-end-of-line (FEOL) as well as back-end-of-line (BEOL) methods in CMOS integration. Neither does the research community address CMOS integration based methods to realize multi and specific target detection that are important attributes for an ideal LOC biosensor. Integration of SiNW with CMOS circuitry will facilitate real time detection of the output signal and in addition provide a compact small sized sensor that is fully portable operating at high speed. In order to avail the benefits of CMOS circuits and develop a large scale production friendly LOC sensor, the scheme of SiNW fabrication has to facilitate either the FEOL or BEOL CMOS integration schemes. This thesis work is focused on revealing a novel FEOL as well as BEOL scheme for integration of SiNW with CMOS circuitry. The major part of the FEOL research work is concentrated on developing a high volume SiNW manufacturing method that is suitable for industrial production. Likewise, in the BEOL scheme, predominant focus was to develop a wafer scale scheme to integrate network of nanowires (nanonets) with CMOS circuitry to manufacture a monolithic 3D above-IC LOC biosensor. In the FEOL scheme, the SiNWs are fabricated using a revised pattern transfer technique called sidewall transf, Kiselnanotrådar har studerats de senaste åren för biosensortillämpningar på grund av deras dimensioner i nanometer skalan som potentiellt möjliggör hög känslighet, etikettfri detektering samt en liten provmängd. Forskningen har varit fokuserad främst på användandet av enskilda eller ett flertal parallella kiselnanotrådar för biosensor tillämpningar, men lite försök har gjorts att integrera kiselnanotrådar med komplementär CMOS teknologi för att erhålla en komplett ”lab-on-chip” (LOC) sensor. Dessutom har tillverkningsmetoderna för kiselnanotrådar som hittills använts för biosensortillämpningar inte fullt utnyttjat möjligheterna som finns med integration i processflödet där transistorn tillverkas (front-end of-line, FEOL) eller i processflödet där metall ledare tillverkas för att koppla ihop transistorerna sker (back-end-of-line, BEOL). Integration av kiselnanotrådar med CMOS kretsar kommer att underlätta realtidsdetektering av sensorns utsignal och också möjliggöra en kompakt sensor som är bärbar. För att utnyttja fördelarna med CMOS kretsar och utveckla en produktionsvänlig LOC sensor så är det fördelaktigt om kiselnanotrådar kan integreras och produceras på samma chip som CMOS kretsarna. Den här avhandlingen fokuserar på nya metoder att integrera kiselnanotrådar i CMOS teknologins FEOL och BEOL processflöden. Ett huvudmål har varit att utveckla en metod att tillverka kiselnanotrådar i stor skala i FEOL med konventionell utrustning för CMOS tillverkning samt att i BEOL utveckla en process för att tillverka en biosensor med ett nätverk av kiselnanotrådar på hela kiselskivor efter metalliseringen. I FEOL flödet har kiselnanotrådar tillverkats med en utvecklad mönsterteknik, kallad ”sidewall transfer” litografi, som utnyttjar konventionella material i CMOS tillverkning. Användandet optisk litografi och selektiva etstekniker möjligör kontroll av linjebredden hos de tillverkade kiselnanotrådarna. Ett fabrikationsflöde för att tillverka CMOS-kretsar med TiN gate elektrod, QC 20181001

Ion sensing represents a grand research challenge. It finds a vast variety of applications in, e.g., gas sensing for domestic gases and ion detection in electrolytes for chemical-biological-medical monitoring. Semiconductor genome sequencing exemplifies a revolutionary application of the latter. For such sensing applications, the signal mostly spans in the low frequency regime. Therefore, low-frequency noise (LFN) present in the same frequency domain places a limit on the minimum detectable variation of the sensing signal and constitutes a major research and development objective of ion sensing devices. This thesis focuses on understanding LFN in ion sensing based on both experimental and theoretical studies. The thesis starts with demonstrating a novel device concept, i.e., ion-gated bipolar amplifier (IGBA), aiming at boosting the signal for mitigating the interference by external noise. An IGBA device consists of a modified ion-sensitive field-effect transistors (ISFET) intimately integrated with a bipolar junction transistor as the internal current amplifier with an achieved internal amplification of 70. The efficacy of IGBA in suppressing the external interference is clearly demonstrated by comparing its noise performance to that of the ISFET counterpart. Among the various noise sources of an ISFET, the solid/liquid interfacial noise is poorly studied. A differential microelectrode cell is developed for characterizing this noise component by employing potentiometry and electrochemical impedance spectroscopy. With the cell, the measured noise of the TiN/electrolyte interface is found to be of thermal nature. The interfacial noise is further found to be comparable or larger than that of the state-of-the-art MOSFETs. Therefore, its influence cannot be overlooked for design of future ion sensors. To understand the solid/liquid interfacial noise, an electrochemical impedance model is developed based on the dynamic site-binding reactions of surface hydrogen ions with

Ion sensing represents a grand research challenge. It finds a vast variety of applications in, e.g., gas sensing for domestic gases and ion detection in electrolytes for chemical-biological-medical monitoring. Semiconductor genome sequencing exemplifies a revolutionary application of the latter. For such sensing applications, the signal mostly spans in the low frequency regime. Therefore, low-frequency noise (LFN) present in the same frequency domain places a limit on the minimum detectable variation of the sensing signal and constitutes a major research and development objective of ion sensing devices. This thesis focuses on understanding LFN in ion sensing based on both experimental and theoretical studies. The thesis starts with demonstrating a novel device concept, i.e., ion-gated bipolar amplifier (IGBA), aiming at boosting the signal for mitigating the interference by external noise. An IGBA device consists of a modified ion-sensitive field-effect transistors (ISFET) intimately integrated with a bipolar junction transistor as the internal current amplifier with an achieved internal amplification of 70. The efficacy of IGBA in suppressing the external interference is clearly demonstrated by comparing its noise performance to that of the ISFET counterpart. Among the various noise sources of an ISFET, the solid/liquid interfacial noise is poorly studied. A differential microelectrode cell is developed for characterizing this noise component by employing potentiometry and electrochemical impedance spectroscopy. With the cell, the measured noise of the TiN/electrolyte interface is found to be of thermal nature. The interfacial noise is further found to be comparable or larger than that of the state-of-the-art MOSFETs. Therefore, its influence cannot be overlooked for design of future ion sensors. To understand the solid/liquid interfacial noise, an electrochemical impedance model is developed based on the dynamic site-binding reactions of surface hydrogen ions with

Ion sensing represents a grand research challenge. It finds a vast variety of applications in, e.g., gas sensing for domestic gases and ion detection in electrolytes for chemical-biological-medical monitoring. Semiconductor genome sequencing exemplifies a revolutionary application of the latter. For such sensing applications, the signal mostly spans in the low frequency regime. Therefore, low-frequency noise (LFN) present in the same frequency domain places a limit on the minimum detectable variation of the sensing signal and constitutes a major research and development objective of ion sensing devices. This thesis focuses on understanding LFN in ion sensing based on both experimental and theoretical studies. The thesis starts with demonstrating a novel device concept, i.e., ion-gated bipolar amplifier (IGBA), aiming at boosting the signal for mitigating the interference by external noise. An IGBA device consists of a modified ion-sensitive field-effect transistors (ISFET) intimately integrated with a bipolar junction transistor as the internal current amplifier with an achieved internal amplification of 70. The efficacy of IGBA in suppressing the external interference is clearly demonstrated by comparing its noise performance to that of the ISFET counterpart. Among the various noise sources of an ISFET, the solid/liquid interfacial noise is poorly studied. A differential microelectrode cell is developed for characterizing this noise component by employing potentiometry and electrochemical impedance spectroscopy. With the cell, the measured noise of the TiN/electrolyte interface is found to be of thermal nature. The interfacial noise is further found to be comparable or larger than that of the state-of-the-art MOSFETs. Therefore, its influence cannot be overlooked for design of future ion sensors. To understand the solid/liquid interfacial noise, an electrochemical impedance model is developed based on the dynamic site-binding reactions of surface hydrogen ions with

Ion sensing represents a grand research challenge. It finds a vast variety of applications in, e.g., gas sensing for domestic gases and ion detection in electrolytes for chemical-biological-medical monitoring. Semiconductor genome sequencing exemplifies a revolutionary application of the latter. For such sensing applications, the signal mostly spans in the low frequency regime. Therefore, low-frequency noise (LFN) present in the same frequency domain places a limit on the minimum detectable variation of the sensing signal and constitutes a major research and development objective of ion sensing devices. This thesis focuses on understanding LFN in ion sensing based on both experimental and theoretical studies. The thesis starts with demonstrating a novel device concept, i.e., ion-gated bipolar amplifier (IGBA), aiming at boosting the signal for mitigating the interference by external noise. An IGBA device consists of a modified ion-sensitive field-effect transistors (ISFET) intimately integrated with a bipolar junction transistor as the internal current amplifier with an achieved internal amplification of 70. The efficacy of IGBA in suppressing the external interference is clearly demonstrated by comparing its noise performance to that of the ISFET counterpart. Among the various noise sources of an ISFET, the solid/liquid interfacial noise is poorly studied. A differential microelectrode cell is developed for characterizing this noise component by employing potentiometry and electrochemical impedance spectroscopy. With the cell, the measured noise of the TiN/electrolyte interface is found to be of thermal nature. The interfacial noise is further found to be comparable or larger than that of the state-of-the-art MOSFETs. Therefore, its influence cannot be overlooked for design of future ion sensors. To understand the solid/liquid interfacial noise, an electrochemical impedance model is developed based on the dynamic site-binding reactions of surface hydrogen ions with

Ion sensing represents a grand research challenge. It finds a vast variety of applications in, e.g., gas sensing for domestic gases and ion detection in electrolytes for chemical-biological-medical monitoring. Semiconductor genome sequencing exemplifies a revolutionary application of the latter. For such sensing applications, the signal mostly spans in the low frequency regime. Therefore, low-frequency noise (LFN) present in the same frequency domain places a limit on the minimum detectable variation of the sensing signal and constitutes a major research and development objective of ion sensing devices. This thesis focuses on understanding LFN in ion sensing based on both experimental and theoretical studies. The thesis starts with demonstrating a novel device concept, i.e., ion-gated bipolar amplifier (IGBA), aiming at boosting the signal for mitigating the interference by external noise. An IGBA device consists of a modified ion-sensitive field-effect transistors (ISFET) intimately integrated with a bipolar junction transistor as the internal current amplifier with an achieved internal amplification of 70. The efficacy of IGBA in suppressing the external interference is clearly demonstrated by comparing its noise performance to that of the ISFET counterpart. Among the various noise sources of an ISFET, the solid/liquid interfacial noise is poorly studied. A differential microelectrode cell is developed for characterizing this noise component by employing potentiometry and electrochemical impedance spectroscopy. With the cell, the measured noise of the TiN/electrolyte interface is found to be of thermal nature. The interfacial noise is further found to be comparable or larger than that of the state-of-the-art MOSFETs. Therefore, its influence cannot be overlooked for design of future ion sensors. To understand the solid/liquid interfacial noise, an electrochemical impedance model is developed based on the dynamic site-binding reactions of surface hydrogen ions with

Over the past 15 years, biologically sensitive field-effect-transistors (bioFETs) employing a nanowire as their active element have become very popular. Each year, many experiments are reported that use nanowire bioFETs to detect and quantify new clinically relevant biomolecules.This thesis aims to enhance our understanding of bioFETs in order to answer important practical questions regarding the operation and optimization of them.We discuss the proper biasing of a bioFET in order to maximize sensitivity. Using electrostatic arguments and MATLAB simulations, we offer a recipe for biasing that applies to biomolecule detection using SOI-based FETs, including nanowire and nanoribbon bioFETs. In contrast to previous works, we take into account the two degree of freedom afforded by a solution-gate and a back-gate. We find that such a bioFET is best operated when the channel is fully depleted. This is in line with the findings of others regarding the biasing of bioFETs using a single gate. We also discuss the opportunity to tune an extra degree-of-freedom: the electric charge on the surface of bioFETs that could be brought by other chemical species, such as linker molecules, probe molecules, or surface groups. We show that an optimum value exists for this surface charge. The optimum amount of charge is that which minimizes the electric field at the solution/bioFET interface prior to analyte capture. We show that this optimum is a result of a minimum in Debye screening strength.We study the electrostatics of a nanowire bioFET as we change the geometry of the nanowire. It is commonly accepted that nanowires with small diameters are more sensitive than larger nanowires because their surface-area-to-volume ratio is larger. We use analytical arguments to show that this analysis is incorrect. Using simulations, we show that analytes captured in concave regions and corners produce a stronger signal due to reduced Debye screening. All structures have such corners, but in small na

Over the past 15 years, biologically sensitive field-effect-transistors (bioFETs) employing a nanowire as their active element have become very popular. Each year, many experiments are reported that use nanowire bioFETs to detect and quantify new clinically relevant biomolecules.This thesis aims to enhance our understanding of bioFETs in order to answer important practical questions regarding the operation and optimization of them.We discuss the proper biasing of a bioFET in order to maximize sensitivity. Using electrostatic arguments and MATLAB simulations, we offer a recipe for biasing that applies to biomolecule detection using SOI-based FETs, including nanowire and nanoribbon bioFETs. In contrast to previous works, we take into account the two degree of freedom afforded by a solution-gate and a back-gate. We find that such a bioFET is best operated when the channel is fully depleted. This is in line with the findings of others regarding the biasing of bioFETs using a single gate. We also discuss the opportunity to tune an extra degree-of-freedom: the electric charge on the surface of bioFETs that could be brought by other chemical species, such as linker molecules, probe molecules, or surface groups. We show that an optimum value exists for this surface charge. The optimum amount of charge is that which minimizes the electric field at the solution/bioFET interface prior to analyte capture. We show that this optimum is a result of a minimum in Debye screening strength.We study the electrostatics of a nanowire bioFET as we change the geometry of the nanowire. It is commonly accepted that nanowires with small diameters are more sensitive than larger nanowires because their surface-area-to-volume ratio is larger. We use analytical arguments to show that this analysis is incorrect. Using simulations, we show that analytes captured in concave regions and corners produce a stronger signal due to reduced Debye screening. All structures have such corners, but in small na

Point-of-care (POC) diagnostics presents a giant market opportunity with profound societal impact. In particular, specific detection of DNA and protein markers can be essential for early diagnosis of e.g. cancer, cardiovascular disease, infections or allergies. Today, identification of these markers often requires extensive laboratory work and hence is expensive and time consuming. Current methods for recognition and detection of specific biomolecules are mostly optics based and thus impose severe limitations as to convenience, specificity, sensitivity, parallel processing and cost reduction. Electronic sensors based on silicon nanowire field-effect transistors have been reported to be able to detect biomolecules with concentrations down to femtomolar (fM) level with high specificity. Although the reported capability needs further confirmation, the CMOS-compatible fabrication process of such sensors allows for low cost production and high density integration, which are favorable for POC applications. This thesis mainly focuses on the development of a multiplex detection platform based on silicon nanowire field-effect sensors integrated with a microfluidic system for liquid sample delivery. Extensive work was dedicated to developing a top-down fabrication process of the sensors as well as an effective passivation scheme. The operation mechanism and coupling efficiencies of different gate configurations were studied experimentally with the assistance of numerical simulation and equivalent circuits. Using pH sensing as a model system, large effort was devoted to identifying sources for false responses resulting from the instability of the inert-metal gate electrode. In addition, the drift mechanism of the sensor operating in electrolyte was addressed and a calibration model was proposed. Furthermore, protein detection experiments were performed using small-sized Affibody molecules as receptors on the gate insulator to tackle the Debye screening issue. Preliminary resul

Point-of-care (POC) diagnostics presents a giant market opportunity with profound societal impact. In particular, specific detection of DNA and protein markers can be essential for early diagnosis of e.g. cancer, cardiovascular disease, infections or allergies. Today, identification of these markers often requires extensive laboratory work and hence is expensive and time consuming. Current methods for recognition and detection of specific biomolecules are mostly optics based and thus impose severe limitations as to convenience, specificity, sensitivity, parallel processing and cost reduction. Electronic sensors based on silicon nanowire field-effect transistors have been reported to be able to detect biomolecules with concentrations down to femtomolar (fM) level with high specificity. Although the reported capability needs further confirmation, the CMOS-compatible fabrication process of such sensors allows for low cost production and high density integration, which are favorable for POC applications. This thesis mainly focuses on the development of a multiplex detection platform based on silicon nanowire field-effect sensors integrated with a microfluidic system for liquid sample delivery. Extensive work was dedicated to developing a top-down fabrication process of the sensors as well as an effective passivation scheme. The operation mechanism and coupling efficiencies of different gate configurations were studied experimentally with the assistance of numerical simulation and equivalent circuits. Using pH sensing as a model system, large effort was devoted to identifying sources for false responses resulting from the instability of the inert-metal gate electrode. In addition, the drift mechanism of the sensor operating in electrolyte was addressed and a calibration model was proposed. Furthermore, protein detection experiments were performed using small-sized Affibody molecules as receptors on the gate insulator to tackle the Debye screening issue. Preliminary resul

Point-of-care (POC) diagnostics presents a giant market opportunity with profound societal impact. In particular, specific detection of DNA and protein markers can be essential for early diagnosis of e.g. cancer, cardiovascular disease, infections or allergies. Today, identification of these markers often requires extensive laboratory work and hence is expensive and time consuming. Current methods for recognition and detection of specific biomolecules are mostly optics based and thus impose severe limitations as to convenience, specificity, sensitivity, parallel processing and cost reduction. Electronic sensors based on silicon nanowire field-effect transistors have been reported to be able to detect biomolecules with concentrations down to femtomolar (fM) level with high specificity. Although the reported capability needs further confirmation, the CMOS-compatible fabrication process of such sensors allows for low cost production and high density integration, which are favorable for POC applications. This thesis mainly focuses on the development of a multiplex detection platform based on silicon nanowire field-effect sensors integrated with a microfluidic system for liquid sample delivery. Extensive work was dedicated to developing a top-down fabrication process of the sensors as well as an effective passivation scheme. The operation mechanism and coupling efficiencies of different gate configurations were studied experimentally with the assistance of numerical simulation and equivalent circuits. Using pH sensing as a model system, large effort was devoted to identifying sources for false responses resulting from the instability of the inert-metal gate electrode. In addition, the drift mechanism of the sensor operating in electrolyte was addressed and a calibration model was proposed. Furthermore, protein detection experiments were performed using small-sized Affibody molecules as receptors on the gate insulator to tackle the Debye screening issue. Preliminary resul

Point-of-care (POC) diagnostics presents a giant market opportunity with profound societal impact. In particular, specific detection of DNA and protein markers can be essential for early diagnosis of e.g. cancer, cardiovascular disease, infections or allergies. Today, identification of these markers often requires extensive laboratory work and hence is expensive and time consuming. Current methods for recognition and detection of specific biomolecules are mostly optics based and thus impose severe limitations as to convenience, specificity, sensitivity, parallel processing and cost reduction. Electronic sensors based on silicon nanowire field-effect transistors have been reported to be able to detect biomolecules with concentrations down to femtomolar (fM) level with high specificity. Although the reported capability needs further confirmation, the CMOS-compatible fabrication process of such sensors allows for low cost production and high density integration, which are favorable for POC applications. This thesis mainly focuses on the development of a multiplex detection platform based on silicon nanowire field-effect sensors integrated with a microfluidic system for liquid sample delivery. Extensive work was dedicated to developing a top-down fabrication process of the sensors as well as an effective passivation scheme. The operation mechanism and coupling efficiencies of different gate configurations were studied experimentally with the assistance of numerical simulation and equivalent circuits. Using pH sensing as a model system, large effort was devoted to identifying sources for false responses resulting from the instability of the inert-metal gate electrode. In addition, the drift mechanism of the sensor operating in electrolyte was addressed and a calibration model was proposed. Furthermore, protein detection experiments were performed using small-sized Affibody molecules as receptors on the gate insulator to tackle the Debye screening issue. Preliminary resul

Point-of-care (POC) diagnostics presents a giant market opportunity with profound societal impact. In particular, specific detection of DNA and protein markers can be essential for early diagnosis of e.g. cancer, cardiovascular disease, infections or allergies. Today, identification of these markers often requires extensive laboratory work and hence is expensive and time consuming. Current methods for recognition and detection of specific biomolecules are mostly optics based and thus impose severe limitations as to convenience, specificity, sensitivity, parallel processing and cost reduction. Electronic sensors based on silicon nanowire field-effect transistors have been reported to be able to detect biomolecules with concentrations down to femtomolar (fM) level with high specificity. Although the reported capability needs further confirmation, the CMOS-compatible fabrication process of such sensors allows for low cost production and high density integration, which are favorable for POC applications. This thesis mainly focuses on the development of a multiplex detection platform based on silicon nanowire field-effect sensors integrated with a microfluidic system for liquid sample delivery. Extensive work was dedicated to developing a top-down fabrication process of the sensors as well as an effective passivation scheme. The operation mechanism and coupling efficiencies of different gate configurations were studied experimentally with the assistance of numerical simulation and equivalent circuits. Using pH sensing as a model system, large effort was devoted to identifying sources for false responses resulting from the instability of the inert-metal gate electrode. In addition, the drift mechanism of the sensor operating in electrolyte was addressed and a calibration model was proposed. Furthermore, protein detection experiments were performed using small-sized Affibody molecules as receptors on the gate insulator to tackle the Debye screening issue. Preliminary resul

Розробляються та вдосконалюються сенсори на основі іон-селективних польових транзисторів(ІСПТ) для дослідження іонного складу розчинів. Для проектування та вдосконалення схем управління сенсорами необхідно визначати порогову напругу ІСПТ за даними технологічного процесу. У статті наведено аналітичний розрахунок порогової напруги p-канального ІСПТ.

Ion-selective field-effect transistors (ISFET) are being developed and improved to study ion solution composition. It is necessary to determine threshold ISFET voltage on the basis of process data for design and improvement of sensor control circuit. The threshold voltage analytical calculation for p-channel ISFET is presented in this article.

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Elemental technologies have been studied to establish the healthcare chip which is an intelligent micro analytical system to detect human health markers from a trail of blood. A two steps process for deep quartz dry-etching was discussed in order to overcome the issues of concave-shaped defects at the bottom of grooves. A coating with 2-methacryloyloxyethylphosphorylcholine (MPC) polymer was studied to suppress the adsorption of bio-substance onto the inner wall of the flow channel on chip and good bio-compatibility was achieved for suppression of protein adsorption and blood cell adhesion. A prototype of healthcare chip was fabricated on polyethylene terephthalate (PET) plate using a micro molding technique. Using this chip, the ion concentrations of pH, Na^+, K^+, Ca^<++> were successfully measured with embedded ion sensitive field effect transistors (ISFET's).

Closed soilless growing systems are introduced on a large scale in horticultural production, to decrease environmental pollution and to increase efficiency and product quality. Applying closed growing systems needs precise knowledge of the composition of the recirculating nutrient solution. This paper presents basic principles of a measur-ing system, which can monitor continuously the concentration of nutrients in water. The sensor system is based on the chemically modified field effect transistor (CHEMFET) that replaces current methods of discontinuous sampling followed by analysis in the laboratory. For obtaining sensors of high durability, polysiloxane membranes have been developed which contain different side groups to tune their intrinsic properties. These polysiloxane membranes show good performance in lifetime experiments. The ion selectivity has been tuned by incorporation of various novel ion receptor molecules, yielding sensors with high selectivity’s for sodium, potassium, calcium, nitrate, phos-phate and dihydrogen phosphate.

The fabrication of pH-sensitive ISFET devices in an unmodified two-metal commercial CMOS technology (1.0 um from Atmel-ES2) is reported. The ISFET devices have a gate structure compatible with the CMOS process, with an electrically floating electrode consisting on polysilicon plus the two metals. The passivation oxynitride layer acts as the pH-sensitive material in contact with the liquid solution. The devices have shown good operating characteristics, with a 47 mV/pH response. The use of a commercial CMOS process allows the straightforward integration of signal-processing circuitry. An ISFET amplifier circuit has been integrated with the ISFET sensors.

In this work an alternative, very simple, high-yield and low-cost technology for the fabrication of backside contacts ISFET sensors is presented. This new technological approach is based on the use of a nickel electroless plating technique for the selective metallization of the silicon electrical contacts. The need of any photolithographic step after the silicon anisotropic etch is avoided in this way and, therefore, the yield and the reliability of the whole fabrication process remains unaffected. The fabricated backside contacts ISFET devices has been tested successfully in a prototype of a whole chemical analysis system dedicated to the monitoring of the environment.