\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"d9159ce31733bf78cc2a79b18c225994",bookSignature:"Dr. Gabriel Cismaru",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11867.jpg",keywords:"Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Restrictive Cardiomyopathy, Transesophageal Echocardiography, Intracardiac Echocardiography, 3-Dimensional Echocardiography, Adult Congenital Heart Disease, Tetralogy of Fallot, Transposition of the Great Vessels, Coronary Artery Disease, Risk Stratification, Revascularization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 21st 2022",dateEndSecondStepPublish:"May 19th 2022",dateEndThirdStepPublish:"July 18th 2022",dateEndFourthStepPublish:"October 6th 2022",dateEndFifthStepPublish:"December 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Cismaru Gabriel is an Assistant Professor at the University of Medicine and Pharmacy Cluj-Napoca, certified in Cardiology. After completing his certification in cardiology, Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu. He has authored or co-authored peer-reviewed articles and book chapters in the field of cardiac pacing, defibrillation, electrophysiological study, and catheter ablation.",coeditorOneBiosketch:"Raluca Tomoaia is an MD, Ph.D. in novel techniques in Echocardiography at the University of Medicine and Pharmacy in Cluj-Napoca, Romania., assistant professor, and a researcher in echocardiography and cardiovascular imaging.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"191888",title:"Dr.",name:"Gabriel",middleName:null,surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru",profilePictureURL:"https://mts.intechopen.com/storage/users/191888/images/system/191888.png",biography:"Dr. Cismaru Gabriel is an assistant professor at the Cluj-Napoca University of Medicine and Pharmacy, Romania, where he has been qualified in cardiology since 2011. He obtained his Ph.D. in medicine with a research thesis on electrophysiology and pro-arrhythmic drugs in 2016. Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France, after finishing his cardiology certification with stages in Clermont-Ferrand and Dinan, France. He began working at the Rehabilitation Hospital\\'s Electrophysiology Laboratory in Cluj-Napoca in 2011. He is an experienced operator who can implant pacemakers, CRTs, and ICDs, as well as perform catheter ablation of supraventricular and ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation. He has been qualified in pediatric cardiology since 2022, and he regularly performs device implantation and catheter ablation in children. Dr. Cismaru has authored or co-authored peer-reviewed publications and book chapters on cardiac pacing, defibrillation, electrophysiological studies, and catheter ablation.",institutionString:"Iuliu Hațieganu University of Medicine and Pharmacy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"5970",title:"Bedside Procedures",subtitle:null,isOpenForSubmission:!1,hash:"ba56d3036ac823a7155f40e4a02c030d",slug:"bedside-procedures",bookSignature:"Gabriel Cismaru",coverURL:"https://cdn.intechopen.com/books/images_new/5970.jpg",editedByType:"Edited by",editors:[{id:"191888",title:"Dr.",name:"Gabriel",surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9064",title:"Epidemiology and Treatment of Atrial Fibrillation",subtitle:null,isOpenForSubmission:!1,hash:"1cd6bf2b3181eb82446347fbe478a2bc",slug:"epidemiology-and-treatment-of-atrial-fibrillation",bookSignature:"Gabriel Cismaru and Keith Andrew Chan",coverURL:"https://cdn.intechopen.com/books/images_new/9064.jpg",editedByType:"Edited by",editors:[{id:"191888",title:"Dr.",name:"Gabriel",surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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By the turn of the twentieth century, contemporary physiological and biochemical investigations had elucidated a few of these poisons’ mechanisms of action.
Additionally, neurochemical alterations should be regarded as harmful even if they are reversible and transient and cause dysfunction. Neurotoxicity can also arise due to indirect effects, such as harm to the cardiovascular or hepatic systems or changes in the endocrine system. Numerous compounds function in various ways and can directly or indirectly affect the neurological system [2].
The nervous tissue present in the brain, spinal cord, and periphery includes an extraordinarily complex biological system that generally describes many of the original traits of individuals. However, as with any profoundly complex system, even minor disturbances to its environment can result in significant functional disturbances. Factors leading to the vulnerability of nervous tissue include a large surface area of neurons, a high lipid content that retains lipophilic toxins, high blood flow to the brain inducing increased effective toxin exposure, and persistence of neurons through an individual’s lifetime, leading to the compounding of damages.
As the nervous system is more vulnerable to toxins, several mechanisms are designed to protect it from internal and external hazards, including the blood–brain barrier. The blood–brain barrier (BBB) and choroid plexus that provide a layer of protection against toxin absorption in the brain. The choroid plexuses are vascularized layers of tissue found in the brain’s third, fourth, and lateral ventricles, which through the function of their ependymal cells, are responsible for the synthesis of cerebrospinal fluid (CSF). Importantly, through the selective passage of ions and nutrients and trapping heavy metals such as lead [1, 2, 3].
Many neurotoxicants function by inhibiting the GABAA receptor, resulting in prolonged closure of the chloride channel and excess nerve excitation (Figure 1). Cyclodiene, the organochlorine insecticide lindane, and some pyrethroid insecticides prove acute neurotoxicity, at least partly through this mechanism. Symptoms of GABA inhibition include dizziness, headache, nausea, vomiting, tremors, convulsions, and death. Other some acts via Na channel inhibitors (tetrodotoxin), K channel inhibitors (tetraethylammonium), Cl channel inhibitors (chlorotoxin), Ca channel inhibitors (conotoxin), inhibitors of synaptic vesicle release (botulinum toxin, tetanus toxin), receptor inhibitors (bungarotoxin), blood–brain barrier inhibitors (aluminum mercury), Ca-mediated cytotoxicity (lead), and toxins with multiple effects (ethanol). In some cases, the hemostasis of energy can be affected [2].
The neurotoxins block the receptors, thus preventing the maintenance of proper physiological function.
Chemicals that disrupt the mammalian nervous system can occur naturally (neurotoxins) or be produced (neurotoxicants). While the term “neurotoxins” refers to substances with neurotoxic potential, this is not an inherent quality of the chemicals but rather a description of the effect that may occur when the tissue concentration surpasses a certain threshold. Neurotoxic biological substances usually demonstrate a high level of target selectivity and toxicity. Microorganisms, reptiles, and vertebrates exhibit direct or indirect neurotoxic effects that are well-understood mechanistically (Table 1) [3, 4].
Life form | Substances with neurotoxic potential |
---|---|
Bacterium | Diphtheria, a toxin |
Fungus | 3-Nitropropionic acid |
Plant | L-BOAA |
Insect | Apamin |
Reptile | Dendrotoxin |
Bird | Batrachotoxin |
Other naturally occurring compounds with less strong qualities have been shown to cause neurotoxicity when administered in high concentrations for a sustained length of time. Metals (arsenic, lead, and mercury) and other elements and compounds, such as selenium and vitamin B6, come into this category. While these chemicals are neurotoxic in high concentrations, they are required in trace levels to maintain proper physiological function, particularly in the nervous system. Natural enzymes (thiaminase) that metabolize necessary chemicals (thiamine) are also associated with neurological disorders in both animals and humans. Synthetic chemicals with neurotoxic potential are most frequently obtained through a prescription (vincristine, ethambutol, isoniazid) and over-the-counter (bismuth preparations) pharmaceutical aisles; (pyridethione) products used in antidandruff shampoos; (2,6-dinitro-3-methoxy-4-tet-butyltoluene) fragrance raw materials; and (acrylamide) pyrolysis products used in broiled, baked. Others are associated with particular applications, such as chemical warfare in military and civilian settings (sarin). Directly neurotoxic substances are supplemented by medications that change neurological function due to their effects on another organ system on which the brain relies for proper operation. This class of medications includes those that target the lung, kidney, and liver particularly, as well as drugs that disrupt the nervous system’s constant supply of oxygen (cyanide, azide) and glucose (glucose) (6-chloro-6-deoxyglucose). Chronic liver failure and manganese toxicity are associated with increased signal abnormalities in the basal ganglia on T1-weighted magnetic resonance images, implying that the metal accumulates due to the liver’s general inability to eliminate it (Table 2) [3, 4].
Substance | Primary neurotoxic effects |
---|---|
Organophosphorus compounds (pesticides and warfare agents) | Cholinergic syndrome (certain compounds), peripheral neuropathy (certain compounds only), acetylcholinesterase İnhibition |
Lead, inorganic | Peripheral neuropathy acute encephalopathy |
Arsenic | Acute encephalopathy peripheral neuropathy |
Mercury, inorganic | Cerebellar syndrome and psychological reactions (anxiety, personality changes, memory loss) |
Methanol | Optic neuropathy extrapyramidal syndrome, retinopathy |
Carbon monoxide | Encephalopathy/ parkinsonism(delayed), neuronal and tissue necrosis secondary to hypoxia |
Phenytoin | Fetal phenytoin syndrome, cerebellar syndrome, chronic encephalopathy (cognitive dysfunction), extrapyramidal syndrome (chorea, dyskinesia), peripheral neuropathy |
Arsenic | Acute severe encephalopathy, peripheral neuropathy |
Tricyclic antidepressants | Seizure disorder (myoclonus), psychobiological reaction (serotonin syndrome, anticholinergic syndrome), tremor, extrapyramidal syndrome (dyskinesia) |
These manifestations include signs and symptoms in multiple parts of the central nervous system, including the central, peripheral, and autonomic nervous systems and skeletal muscle. They are typically accompanied by discomfort, altered sensations, such as taste and smell, decreased visual acuity, and hearing loss [5, 6].
Acute encephalopathies are a common occurrence. The majority are insignificant and dissipate within a few days. Headache, weariness, disorientation, loss of attention and short-term memory, lack of motor coordination, and the resulting gait irregularity, nausea, and dizziness are the most common indications and symptoms. Schaumburg identified several compounds (about 100) as possible causative factors, including aluminum, cannabis, cocaine, domoic acid, lead, organic solvents, and trimethyltin. While acute symptoms commonly resolve rapidly, chronic issues can significantly debilitating influence on job performance and productivity. There is a significant need for long-term follow-up and mental and psychological disorders assessment. Acute (moderate) encephalopathy rarely progresses to chronic (severe) encephalopathy with progressive cognitive and psychomotor impairment [5, 6, 7].
Cerebellar dysfunction, manifested by ataxia, intention tremor, and lack of coordination, is well documented due to chronic mercury exposure; however, overdose with various potentially lethal medications and substances, including 5-fluorouracil, lithium, and acrylamide, has also been reported. Cerebellar dysfunction is notoriously challenging to diagnose. Extrapyramidal syndromes such as parkinsonism, dystonias, dyskinesias, and tics are relatively well-defined toxic syndromes. While the destructive processes are unknown, they are frequently reversible, although symptoms can return years after the condition begins. Parkinsonism is arguably the most well-known form of Parkinson’s disease, owing to an epidemic involving people exposed to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a contaminant found in certain illicit substances. Most syndromes are induced by excessive medication use, particularly phenothiazines, rather than by exposure to non-therapeutic drugs [6, 7, 8, 9].
Loss of taste and smell and changes in smell and taste are common complaints that are difficult to quantify accurately, and quantitative procedures are not always practical. Despite the frequent involvement of organic solvents, this illness lacks a well-defined pathophysiological basis. Among the problems inherent in quantifying taste is that olfaction plays a significant role in detecting food’s “flavor” and “perfume,” even though many of us would categorize these as tastes. Changes in taste perception are frequently connected with administering a variety of therapeutic medicines. However, they are typically reversible. Although hearing loss has been associated with using organic solvents, particularly toluene, it is more usually associated with well-known ototoxic drugs such as aminoglycosides [6, 7].
Typically, vision loss occurs as a direct result of a toxic or corrosive material striking the cornea and conjunctiva or because the lens loses its transparency due to cataract formation. Direct attacks on the neuronal components of the visual system are less common than indirect attacks. Mydriasis and miosis are two distinct symptoms caused by exposure to or use of parasympathomimetic medications, anticholinesterase inhibitors, and parasympatholytics such as atropine. Nystagmus can develop as a side effect of certain medications, including phenytoin and antibiotics (aminoglycoside). Neurotoxic exposure is rarely associated with direct retinal injury despite a possible association with specific therapeutic medications. Both toluene (which induces demyelination) and hexachlorophene can cause optic nerve injury (leading to deformation of myelin). Alcohol addiction (methanol or ethanol) is also associated with widespread damage of the neuronal components of the visual system. Nonetheless, the etiology is suspected to be compounded by many chronic alcoholics’ nutritional deficiencies [6, 7].
These are frequently mistaken with axonopathies. However, the terms do not refer to the same thing. Peripheral neuropathy can develop within the neuron, resulting in the death or dysfunction of cells (in which case we call a neuronopathy). Axon degeneration (axonopathy) or loss of neuronal or axonal function may occur when the myelin sheath is disrupted. Channelopathy may develop from a change in the function of ion channels, or the toxin may target nerve terminals (leading to a neuromuscular transmission syndrome). Neuronopathies are easily recognized since they are much more likely to be sensory in origin and affect areas supplied by the injured neurons. The mechanisms by which they cause harm are not well understood. Methyl mercury is the neurotoxin most frequently connected with this illness. Proprioception may be compromised before or more severely than subsequent pain, whereas nerve conduction velocity and muscular strength are preserved. Healing is unpredictable, as neurons may survive or perish as a result of the toxic insult. Demyelinating neuropathies affect the peripheral nervous system when the Schwann cell or internode’s myelin sheath is damaged. Diphtheria toxin can cause segmental demyelination by damaging the Schwann cell. Hexachlorophene and perhexiline have also been associated with myelin disturbance. Recovery is dependant upon the activation and replication of surviving Schwann cells. Regenerated internodes are slightly shorter than typical in length, myelin sheaths are thinner, and nodes can be somewhat longer than usual. Remyelinated axons conduct at a slower pace in general. Axonopathies are lesions of the peripheral nervous system produced by axon destruction. The presenting signs and symptoms typically manifest gradually and initially impact the long axons and distant locations. Sensory symptoms predominate over motor problems, and ankle reflexes degrade fast. The signs and symptoms then spread proximally for the duration of the axon’s “regeneration.” Healing occurs as a result of damaged axon regrowth. Recovery is often slow due to the 0.5–3.0 mm per day rate of axonal development. Numerous industrial chemicals, such as acrylamide, arsenic, carbon disulfide, n-hexane, lead, organic mercury, and thallium, have been shown to cause axon damage. While recovery is often uncomplicated, chronic ataxia, stiffness, and hyperreflexia can occur following severe poisoning. Axonal channelopathies are caused by aberrant ion channel activity and manifest as faulty axonal conduction. These are typically made up of natural toxins. The motor nerve terminal is a major target for a range of natural neurotoxins (clostridial toxins, cone snail toxins, snake, spider, and scorpion venoms), all of which induce harm to the nerve terminal. What is unknown is the involvement of the nerve terminal in the expression of toxic insult induced by a variety of harmful substances, including organophosphates and acrylamide, both of which have been shown to cause considerable nerve terminal damage. It is unsurprising that most axonopathies that die back originate at the nerve terminal [6, 7, 9].
Skeletal muscle injury is rather infrequent. The bulk of toxicological problems in skeletal muscle is the result of genuine denervation. Several myotoxic substances, including clofibrate and related compounds such as insecticides and organophosphates, can cause substantial muscle loss by rhabdomyolysis. Diazacholesterols and herbicides containing chlorophenoxyisobutyric acid stimulate myotonic activity, whereas licorice, diuretics, and excessive alcohol use induce hypokalemic paralysis. Skeletal muscle regenerates rapidly following the removal of the causative factor. Rhabdomyolysis’s most important acute clinical consequence is a significant risk of acute renal failure [6, 7, 8, 9].
Depression is the most frequently reported symptom of neurotoxic diseases in patients. These individuals frequently express feelings of depression, anxiety, and forgetfulness. While the psychological signs of aluminum toxicity are normally mild, they can progress to severe dementia and parkinsonism/dementia syndrome. Lithium overdose with lysergic acid diethylamide may result in cerebellar ataxia, dementia, and severe psychotic illnesses (LSD). Due to widespread disdain for psychiatric/psychological disorders, there is a dearth of reliable knowledge regarding the diagnosis, management, and prognosis of mental health complaints associated with such intoxication. Additional study on the acute and chronic effects of neurotoxic drugs on cognitive function is necessary [6, 7].
While substances that lead to neurotoxic effects can be found by routine toxicity screening testings (e.g., chronic, acute, developmental/reproductive toxicity), specific standards exist to further evaluate compounds’ potential neurotoxicity. The requirements established by the USEPA (the United States Environmental Protection Agency) are based on a functional observational battery, motor health assessments, and neuropathological examinations. Similarly, the OECD (Organization for Economic Cooperation and Development) criteria emphasize clinical results, practical test findings (e.g., motor activity, sensory response to stimuli), and neuropathology. These batteries are intended to provide a Tier 1 screening for neurotoxicity, with positive findings necessitating additional testing (Tier 2), which may involve specialized behavioral tests in addition to electrophysiological and neurochemical data. Examples include memory and learning tests, nerve conduction velocity measurements, and biochemical tests linked to neurotransmission or indices of cell integrity or function. Specific recommendations for developmental neurotoxicity (DNT) testing have also been created in the United States of America and Europe. The mother is exposed to the test drugs from prenatal day 6 to postnatal day 10 or 21, ensuring exposure both in utero and via maternal milk. The examinations cover developmental milestones and reflexes, motor activity, hearing testing, learning and memory tests, and neuropathology. DNT has been demonstrated to be exceedingly practical and beneficial in detecting substances and agents that have the potential to cause developmental neurotoxicity during neurotoxicity testing. However, additional effort is needed to improve these tests, either because they are susceptible and generate a significant proportion of false positives or because they are insufficiently sensitive and thorough [8, 9, 10, 11].
Additionally, concerns have been expressed about historical control data, toxicokinetic parameters, toxicity mediated by the mother versus direct effects, test selection, and their analysis and interpretation. Toxicologists have increasingly recognized the need for acceptable and accurate alternatives to conventional animal testing in recent years, highlighting the issues associated with rising costs and time requirements for toxicity assessment tests, the growing number of chemicals being developed, and commercializing the demand in response to recent legislation and efforts to reduce the number of animals used in toxicity testing. This, combined with efforts in the field of developmental neurotoxicity, has resulted in the development of alternative models, either using mammalian cells
Neurotoxic effects linked with developmental exposure during pregnancy, nursing, early childhood, and adolescence are frequently documented following a brief period of exposure. Nonetheless, evidence indicates that the insalubrious effects of toxicants may take months, if not years, to manifest clinically. The “silent” phase refers to the time period during which an individual may display no signs or symptoms of poisoning. Silent toxicity is a term that refers to continuing morphological or biochemical damage that is clinically undetected unless concealed by special techniques. Silent toxicity is comparable to carcinogenesis, in which cellular and molecular damage develop years, if not decades before clinical symptoms show. This area contains numerous instances of silent poisoning. Parkinsonism-dementia, frequently referred to as Guam’s disease, is the most widespread kind, with a latency of several decades between supposed yet-undefined exposures and clinical manifestations. Another case of bovine spongiform encephalopathy (mad cow disease) is a form of Creutzfeld–Jacob disease with a documented latency of decades [8, 15, 16, 17, 18, 19]. The time interval between the onset of clinical symptoms and exposure to a neurotoxic event can be explained by a number of factors. For example, while a specific population of neurons may be injured, the brain’s plasticity may compensate for this loss temporarily. Exogenous stressors (stress, illness, chemical exposure) or the normal aging process, on the other hand, may disclose the silent toxicity. Alternatively, an organism may be capable of compensating for a specific defect. Nevertheless, persistent loss of function may eventually exhaust the brain’s functional reserve and plasticity. The likelihood of such a latent period occurring between exposure and clinical manifestation occurring throughout the development stage is significantly greater. David Barker was a pioneer in establishing the possibility that many adult disorders have fetal origins. The “Barker hypothesis” is the name given to this concept. Toxic substance exposure has the potential to directly destroy or modify developmental programming, resulting in later-life functional impairments [8, 9, 19, 20, 21, 22]. Diethylstilbestrol is the most prominent example, which may contribute to an increase in vaginal adenocarcinoma around puberty as a result of in utero exposure. Perinatal exposure of rats to the Gram (−) bacteriotoxin lipopolysaccharide causes a 30% loss in dopaminergic neurons in the substantia nigra and persistent injury to the dopaminergic system, implying that, in humans, prenatal infections occurring at a specific gestational age may result in the birth of an individual with significantly fewer dopaminergic neurons. This could be an example of developmental neurotoxicity. This may seem minor, given that Parkinson’s disease does not manifest clinically until around 80% of dopaminergic neurons are lost completely. When the aging process culminates in the typical progressive loss of dopaminergic neurons, this early-life lesion may play a substantial role in an individual’s development of Parkinson’s disease. Exposure to some pesticides during development, such as the herbicide paraquat and the fungicide maneb, both of which act on dopaminergic neurons, has also been related to the development of Parkinson’s disease later in life. Similarly, developmental exposure to the now-banned organochlorine insecticide dieldrin has been found to cause significant and long-lasting alterations in the dopaminergic system, as well as a silent dopaminergic dysfunction. Rarely, modest and mild injuries may worsen as an individual develops and ages. In this manner, the neurotoxic effects of embryonic MeHg exposure do not manifest themselves for years. Microencephaly produced by uterine exposure to methyl azoxy methanol resulted in an early loss of cognitive abilities, and the neurotoxic consequences of neonatal exposure to triethyltin, a glial neurotoxicant, were increased with age. This cannot be the case in all other situations. Nonetheless, developmental exposure appears to have irreversible neurotoxic effects, and even if they do not deteriorate with age, they have long-term ramifications, as evidenced by perinatal lead exposure [23, 24, 25, 26, 27, 28].
The treatment of neurotoxicity involves terminating, eliminating, or reducing dangerous chemicals and commencing therapy to reduce symptoms and offer necessary support [2, 3].
The difficulty is that if biotoxicity or neurotoxicity is the underlying cause of the pain or sickness and the treatment plan does not include a detoxification regimen, the overall recovery will almost certainly be incomplete and take longer than necessary [2, 3].
Biotoxicity/neurotoxicity treatment protocol can also include acupuncture, herbal remedies & nutritional supplements, nutritional counseling, and prescription of medication. For example, the key factors in the initial management of acute arsenic intoxication are gut decontamination and hemodynamic stabilization in patients with suspected acute arsenic poisoning. Generally, in such neurotoxicity, rapid stabilization with fluid and electrolyte replacement in an intensive care setting is very important. Aggressive intravenous fluid replacement therapy maybe even life-saving in serious poisoning. Gastric lavage may also be useful soon after acute ingestion to prevent any further absorption. The efficacy of activated charcoal is controversial, but its administration together with a cathartic (such as sorbitol) is frequently recommended, but if profound diarrhea is present, cathartics must be withheld. Hemodialysis may be beneficial in a patient with concomitant renal failure. Chelating agents administered within hours of arsenic absorption can successfully prevent the full effects of arsenic toxicity. If patients are treated within several hours after arsenic ingestion, chelation is likely to be beneficial. Therefore, even if arsenic ingestion is only suspected but not confirmed, consultation with a clinical specialist with expertise in the treatment and management of arsenic poisoning is essential [29].
Generally, neurotoxicity has a prognosis and outcome that are determined by the extent and duration of toxic substance exposure and the extent of brain damage. In some cases, individuals die due to neurotoxins exposure, while others live but do not fully recover. The patient may recover entirely following the necessary treatment [2].
The potential threats to human health posed by hazardous chemicals in the surrounding environment have become a significant public health concern. It is critical to have the necessary abilities, tools, and facilities to study neurotoxicity in an individual. Treatment for patients exposed to environmental neurotoxins is not yet defined, and multidisciplinary teams will be necessary to manage the most severe cases. Diagnostic indicators for neurotoxic diseases based on rapid-response biomarkers should be identified and developed more efficiently to be used by all centers. Two essential variables should be considered—the severe effect on the developing fetus and newborn, the long-term health consequences of chronic exposure to low levels of environmental neurotoxins, and the long-term health consequences of severe acute poisoning in patients.
Additionally, a conclusive study is needed to address the frequent allegation that putative neurotoxins lack a “safe” limit, owing to our inadequate understanding of the lethal synergy that can occur when multiple toxins are exposed concurrently. Additionally, significant progress is anticipated in elucidating the relationship of harmful environmental chemicals and susceptibility risk factors in progressive neurodegenerative diseases such as motor neurons, Parkinson’s disease, and Alzheimer’s disease [2, 3, 4].
Neurotoxicity refers to the direct or indirect effect of chemicals that disrupt the nervous system. Neurotoxins can be found naturally in the environment, and they could be synthetic. Some neurotoxins act directly on neural cells; others interfere with metabolic processes on which the nervous system is primarily dependent— The effects of neurotoxicity can appear and disappear rapidly, evolve slowly over days or weeks, regress over months or years, or cause permanent deficits. Neurotoxicity is usually self-limiting after exposure ceases and rarely progressive in the absence of continued exposure. The treatment is terminating the toxins exposure and providing symptomatic treatment.
Active matrix OLED (AMOLED) displays are today’s mainstream consumer displays available in various form factors, such as smart watches, mobile displays, and large area television. They are highly appealing because of their wide viewing angles, nice color saturation and great potential for curved, flexible and/or rollable format. There are several options for (flexible) backplane technologies based on thin-film transistors (TFTs), namely, metal-oxide TFTs (such as indium gallium zinc oxide or IGZO), low-temperature polycrystalline silicon (LTPS) TFTs, or a combination of IGZO and LTPS, more precisely LTPO or low-temperature polycrystalline silicon and metal oxide. All these technologies have their pros and cons. Among others, IGZO semiconductors are n-type only which is sufficient for a backplane driving an OLED but is less adequate for peripheral circuits. Another key important asset of IGZO is the ultralow source-drain leakage current due to the large bandgap of the semiconductor, enabling long retention times of data storing, i.e., pixels are not leaking. In contrary, LTPS has both n- and p-type devices and thus the capability of CMOS circuits. LTPS transistors can drive larger currents due to the intrinsically higher mobility, enabling complex in-pixel compensation schemes and peripheral circuits. However, with LTPS transistors the leakage will be larger. This is a key reason why LTPO has been developed: this technology combines the ultralow leakage current of IGZO and a p-type LTPS transistor resulting in a hybrid complementary technology. An OLED is an organic LED emitting light directly proportional to its forward current. Therefore it requires a current source as driver in the pixel. In many cases, this is achieved by placing a TFT in series with the OLED and driving it in saturation.
\nIn this chapter, we will investigate the potential to embed additional functionalities in the display. Therefore, several strategies will be discussed focusing on improving the resolution of the current displays, by technology optimization introducing photolithography patterning of the OLED and by design evaluating external compensation vs. internal compensation. The extra space in the pixel, due to the combination of photolithography and simple pixel circuit, provides opportunities to include extra functions at the same original area. The focus in this book chapter is to add a photosensitive detector for fingerprint and palmprint readout.
\nResolution (number of pixels) and pixel pitch (size and spacing of pixels) are two main parameters defining the architecture of the display arrays. The first, expressed typically in megapixels, is standardized by the content type, resulting in different generations of TVs: VGA, full HD, 4K, and, most recently, 8K. The latter, expressed typically in pixels per inch (ppi) or pixels per degree (ppd), is used as a benchmark for smartphones, with high-end models featuring densities in the range of 600 ppi. This is a value that gives a good enough image quality for hand-held devices, with the viewing distance of approximately 30 cm (1 foot). At the same time, future near-to-eye augmented reality/virtual reality (AR/VR) displays impose ultrahigh definition, as the pixel density needs to be beyond the pattern resolving capabilities of the human retina (30 cycles per degree) [1, 2]. The resolution should be maximized to provide the highest possible output within the eye box in any given point of the 180° field of view (FOV), also to enable foveated rendering. An aperture ratio close to unity will eliminate the screen door effect and ensure natural experience. Transparency is necessary to avoid sense of isolation from the real-world view and to diversify from the virtual reality (VR) headsets (Figure 1). To realize all of the above, we need both the microdisplay-like pixel pitch down-scaling [3] and the flat-panel-display-like (FPD) backplane size up-scaling [4, 5]. Switching to advanced nodes in flat panel backplane manufacturing can result in ultrahigh-definition, direct-view AR displays fabricated in a cost-effective way.
\nColor-by-white vs. RGB OLED frontplane can be fabricated on top of CMOS or TFT backplane. Each combination is suitable for different applications.
In order to realize an ultrahigh resolution display, all elements of the system (backplane, frontplane, and driving) need to provide appropriate pixel density. On the frontplane side, several options for the light source can be chosen (Figure 2). OLED technology currently dominates the smartphone display industry not only with performance but also with the cost structure. In this case, the colors are defined by depositing separate device stacks for each color, which is typically referred to as side-by-side, red-green-blue (RGB) array. In OLED TVs, one common white OLED stack is combined with a color filter array (CFA). The limitation of the side-by-side RGB array is the pixel density, limited by the fine metal masking (FMM) technology, which uses deposition through a metal mesh. The white OLED array can achieve very small pixel pitch, which is only limited by the backplane and CFA resolution but imposes brightness loss due to CF transmission. Patterning multicolor OLEDs by photolithography can address the needs of ultralow pixel pitch for the future AR displays by realizing side-by-side OLED stacks with extreme density.
\nVarious display configuration options.
Patterning OLEDs by photolithography is an emerging, disruptive fabrication technique. The main challenge is the extreme chemical sensitivity of OLED materials with solvent, moisture, air, and temperature exposure responsible for performance degradation. The choice of appropriate photolithography chemistry is crucial, with fluorinated [6] or non-fluorinated systems [7] as the dominant options. Figure 3 shows the concept of using a negative-type photoresist to define patterns on top of OLED in a subtractive approach. First, the OLED stack is deposited as a plain layer over the entire substrate, on top of a pixel definition layer (PDL). This defines the active area of the light emitter. Second, photoresist is deposited on top of the entire substrate. Then, it is exposed through a lithography mask and developed to obtain the required pattern. Afterwards, the OLED layers that are not covered by the photoresist are etched away (typically with dry etching, such as reactive ion etch). In the end, the photoresist is stripped to achieve patterned OLED islands.
\nProcess flow for photolithography patterning of OLED stacks.
Photolithography allows pattern transfer beyond 1 μm resolution, enabling high-density lines and spaces. Transfer of small islands means that, with appropriate alignment (e.g., with an i-line stepper), a pixel density of a few thousand pixels per inch (ppi) can be realized. Transfer of openings means that pixel spacing can be minimized, resulting in a high aspect ratio. This is applicable for both TFT-based flat panel displays and CMOS-based microdisplays. Tests on patterning the OLED emission layer have shown that it is possible to achieve 1 μm pitch lines and spaces (Figure 4). Furthermore, the photoluminescence signal of the EML is maintained proving compatibility of this process with OLED material. 1 μm presented here is not a fundamental limit of the approach but rather a limit of the lithography mask design used in the experiment.
\nOLED patterns of 1, 2, 3 and 4 μm: optical and corresponding photoluminescence pictures of red EML patterned as lines (left) and spaces (right).
The achievable pixel density of the frontplane is limited not only by the photoresist used but also by the critical dimension (CD) and alignment/overlay accuracy of the litho tools used. In the i-line steppers typical for flat panel manufacturing, the achievable CD is 1.5 μm with an overlay between 0.25 and 0.5 μm. In contrast, CMOS fabs used for microdisplay manufacturing feature more advanced semiconductor nodes, with 248 nm KrF or 193 nm ArF light sources. Assuming a minimum PDL opening (defining the active area) of 500 nm, a 1.5 μm node imposes a density limit of 3500 ppi (for RGB) with an aperture ratio below 5%. Going to KrF steppers, the achievable density increases to 10,000 ppi while keeping the aperture ratio above 35%. This demonstrates the need of a tooling upgrade for future AR displays, both for the frontplane and the backplane. Denser and more efficient packing of pixels requires scaling down of the technology node, especially in FPD manufacturing.
\nOLED patterning by photolithography means that the deposition of the stack is interrupted (vacuum break) and the photoresist interacts with the organic materials. In the most simple case, the photolithography process is performed in a clean room in ambient atmosphere. The devices are loaded back into the glove box after the etch step for each color and after the photoresist strip when all colors are finished. This raises a serious challenge for the device lifetime. If the process is not optimized for compatibility with the stack, the current-voltage-luminance (IVL) curve shifts to the right (increased turn-on voltage) and to the bottom (reduced luminance). As a consequence, the brightness of the patterned OLED drops very fast and disappears even after a few minutes (Figure 5). Optimization of the photoresist system, of the OLED stack [8] and of the fabrication process, is needed to achieve OLED performance enabling implementation into devices. At imec, we demonstrated phosphorescent green OLED with T90 lifetime of >150 h at the starting brightness of 1000 nit. Efficiency remained above 85 cd/A before and after patterning. Current performance is considered an important step on the path to industrial technology readiness level, estimated to be T97 of at least 1000 h (for the green stack) [8].
\nIVL and lifetime curves for reference OLED and the possible effects of degradation by patterning.
\nFigure 6 shows an example comparison of unpatterned and patterned OLED lifetime curve at initial brightness of 1000 nit. The performance improvement can bring the two curves closer together.
\nLifetime curves of a phosphorescent green OLED at 1000 nit starting brightness for unpatterned and patterned stack.
OLED photolithography was used to fabricate passive displays with a 1400 × 1400 pixel array (almost 2 megapixels). 6 μm metal lines and 10 μm line pitch with SiN pixel definition layer (PDL) were used on glass substrate. Green and red OLED stacks were deposited by thermal evaporation in ultrahigh vacuum. After deposition of the first color (until above emission layer), photoresist was spin-coated, baked, exposed, and developed. Then, the OLED stack not covered by the photoresist was removed by dry etching. After that, the sample went back to the ultrahigh vacuum chamber for second color deposition, and the patterning process was repeated, this time finishing with stripping the photoresist. A semitransparent top contact stack was subsequently deposited, and the display was encapsulated with cavity glass. Both colors can be driven separately, and the PDL design allows for emission of a fixed image specified for each color (Figure 7). Subpixel pitch of 10 μm resulted in smooth edges and excellent feature representation. The device was tested for tens of hours with both colors on. No drop of brightness nor appearance of defects could be observed [9].
\nPassive 1250 ppi patterned OLED display with 1400 × 1400 pixels, 10 μm subpixel pitch, and independent color driving: general view (left) and detailed view for different color drivings (right).
This fabrication process is compatible with both CMOS backplanes and flexible TFT backplanes. The frontplane can thus be implemented in an active matrix display. Of course, photolithography can be used several times to realize more colors for a full-color display.
\nTo increase the display resolution, not only the technology (backplane and frontplane) but also the pixel driving techniques should be optimized. The OLED light output is dependent on the drain current of the driving TFTs of the AMOLED displays. Due to inherent variations in AMOLED displays, some compensation methods to the drain current of the TFTs are required to achieve uniform brightness. This can be implemented through either in-pixel compensation [10] or external compensation [11, 12]. Since in-pixel compensation schemes typically require more transistors inside the pixel, external compensation methods are preferred for high-resolution applications. Figure 8 shows pixel circuits and a possible layout for in-pixel compensation, using an 8T1C [10] pixel, and external compensation using a 3T2C [11] and, respectively, a 2T1C [12] pixel. For all these layouts, the same design rules were used. It is clear from this figure that a display with external compensation, especially the 2T1C pixel circuit, can achieve a much higher pixel density.
\nPixel circuits and corresponding layouts for (left) 8T1C, (middle) 3T2C, and (right) 2T1C pixels.
The achievable pixel density depends on both the pixel circuit and the design rules imposed by the technology, such as the critical dimension (CD) of the lithography tool. Figure 9 compares the achievable resolutions for different CDs for the 8T1C, the 3T2C, and the 2T1C pixel circuit. Although the CD of 1.5 μm, as currently achievable with typical i-line steppers, only yields a maximum pixel density of 565 ppi for the 8T1C pixel circuit, the same CD already yields a significant improvement for the pixel circuits using external compensation, namely, 847 ppi for the 3T2C pixel circuit and 1210 ppi for the 2T1C pixel circuit, respectively. Furthermore, improvements in technology allowing smaller CD will even further increase the achievable pixel density, up to 9070 ppi for the 2T1C pixel circuit, when using a CD of 0.2 μm.
\nPixel resolution vs. critical dimension (CD) for various pixel schemes.
The compensation principle for the 3T2C pixel circuit relies on the fact that applying a voltage on the backgate of a transistor will shift the threshold voltage (VT) of that transistor. By applying the correct compensation voltage to the backgate of the drive transistor of each pixel, all VT variations can be eliminated, resulting in a more uniform display. This compensation method uses three different modes of operation for the display. The first mode of operation is the calibration mode. In this mode, the correct compensation voltage is determined for each pixel by applying a certain reference voltage to the frontgate and measuring the current through the pixel while varying the backgate. When the measured current matches a predetermined reference current, the voltage on the backgate is the correct compensation voltage, which will be stored both on the capacitor connected to the backgate and in external memory. Once the correct backgate voltage is set for every pixel, the display can be switched to normal operation. In this mode, the display is driven with the normal video data, which is written to the frontgate of each pixel. Since the CAL signal is low in this mode, the charge on the capacitor will remain, and hence the backgate voltage will be the compensated voltage. However, due to leakage, this charge will slowly change over time. Therefore, a third mode of operation is added, namely, the calibration refresh. In this mode, the SEL signal is kept low, but the CAL signal is running through the display, while the compensation data is applied to the data lines. This way the compensation voltage is restored on the backgate, to ensure the VT uniformity remains over time. This compensation method shows a significant improvement in current variation, as demonstrated in Figure 10.
\nCurrent variation of a 3T2C display before and after compensation.
The current through the drive TFT (IDS), and thus through the OLED, when operating in saturation regime can be calculated for a certain data voltage (VGS) by using Eq. (1):
\nCompensating only for VT can eliminate variations in current for one gray level; however, if the β-factor is different for each pixel, the current will still vary for different gray values, even after VT compensation. This is shown in Figure 11 for the 3T2C pixel. As a consequence, we propose a new compensation method to compensate for both β and VT variations. Similarly as the previous described compensation method, we will first characterize the current through each pixel for multiple data voltages, whereafter the measurements are fitted to Eq. (1).
\nCurrent variation of a 3T2C and 2T1C display before and after compensation.
For each pixel, the extracted β and VT values are stored. Based on these values, the VGS voltages can be calculated for each pixel by the driver IC for each desired gray level by using Eq. (2):
\nThis calculation is relative simple and straightforward, as it only requires a multiplication, a subtraction, and a square root calculation, which enables to display real-time video content by using this methodology. Figure 11 shows the current variation improvements directly obtained from our AMOLED displays, by utilizing the VT-only compensation method and comparing it to the VT and β compensation method. As mentioned above, the simple VT compensation method provides good variation results for a small range, whereas the combined parameter method improves the variation across all desired gray levels.
\nFingerprint sensor arrays (Figure 5.1) [13] are becoming a mainstream security mechanism for mobile devices and are today available as autonomous silicon-based component. The integration of the fingerprint sensor array together with AMOLED displays [14, 15, 16] would benefit the footprint of the mobile device and the functionality, enabling detection of multiple fingers at once or even a palmprint.
\nFingerprint sensors combined with AMOLED displays can be realized in three different configurations for the sensor pixels: (1) in the same plane of the display pixels and (2) under and (3) over the display pixels (Figure 12). With sensors in the same plane, the display module gains optical sensing capability by incorporating photodetector pixels between OLED pixels. Sensors, under or above the display, require a separate fingerprint module. A fingerprint module under the display would need a semitransparent display and light scattering management. A fingerprint module over the display requires a transparent imager to avoid changes in display emission. In the previous section, we have demonstrated that a higher resolution backplane can be achieved at the same critical dimension by introducing external compensation methods. This combined with the photolitho-based patterning method of OPD and OLED will the crucial enablers for such a configuration as analyzed in Paragraph 3.
\nFingerprint integration configurations in AMOLED displays.
The pixel circuit architecture of the sensor array can be either passive or active [17]. The passive pixel is depicted in Figure 13 and is comprised by the photoelement, a capacitor, and a select TFT. The main difference of the active pixel is that it requires an extra TFT acting as a local amplifier. For high-resolution applications, the active pixel is not recommended, since its footprint is larger than the footprint of passive pixels.
\nBlock diagram of the proposed in-panel fingerprint sensor array with integrated CSA for each line, multiplexer (MUX), and ADC. Power and driving electronics remain off-panel.
The integration of peripheral readout circuitry in panel side-by-side with the display peripherals is beneficial for resolution, connectivity, and potential lower system cost of the device. In this paragraph TFT-based integrated readout is demonstrated by using our IGZO n-type only TFTs.
\nThe necessary blocks to implement an in-panel readout system are a charge sense amplifier (CSA), a multiplexer (MUX), and an analog to digital converter (ADC). The CSA is reading out the charge stored in each pixel of the array. The MUX is multiplexing the CSA outputs directly to the ADC, decreasing the number of the required ADC converters. The ADC is converting the analog voltage received from the CSA to a digital code. Various TFT-based analog blocks have been demonstrated in the literature [18, 19, 20, 21, 22, 23, 24]. Metal-oxide TFT technologies are preferable due to uniformity over large areas, very low leakage currents, and lower cost over area. In the following section, fast and small footprint ADCs and charge sense amplifiers (CSA) are discussed to meet the specifications of an in-panel fingerprint array.
\nIn Figure 13, the high-level block diagram of the in-panel readout system is shown. The five main blocks are detailed: a two-dimensional (2-D) image sensor array, the CSAs connect on each row of the array, a multiplexer connects four or more rows (MUX), and ADC connects to every MUX and off-panel power and driving electronics. Each column of the 2D image sensor array is readout from the corresponding row by a CSA. The pixels are readout subsequently enabled by the “SELECT” signals from the columns and converted to digital code through the MUX and an ADC. The MUX enables a larger footprint for the ADC, up to 4 to 8 times larger compared to a single line (50 μm). Hence, the ADC and MUX needs to be 4 to 8 times faster than the CSA. A 1–2 fps readout of 1M pixel imager (1000 × 1000 pixels) sets a readout speed of 1–2 kS/s per line for each CSA. This translates to 4–8 kS/s for the ADC if a 4:1 MUX is used or 8–16 kS/s for a 8:1 MUX. The slower ADC configuration sets the specification limitation to the width of the ADC to 200 μm, whereby the faster allows a width of 400 μm.
\n\nFigure 14 (a) depicts the cross section of the dual-gate self-aligned metal-oxide (MO) technology on a 15-μm-thick polyimide film [25, 26]. The metal-oxide (IGZO or ITZO) TFTs are fabricated with two metal gates (M0, M1) and source-drain metal contacts (M2). An additional metal layer (M3), not shown in the cross section, is beneficial for footprint but also for performance and noise. The CSA experimental results shown in the following sections are designed with an extra metal layer, also used as anode layer.
\n(a) Cross section of dual-gate self-aligned metal-oxide technology on flexible polyimide substrate and (b) extracted on-current (ION) from experimental data of 480/20 (μm/μm) dual-gate self-aligned ITZO (red) and IGZO (orange) TFTs.
\nFigure 14(b) shows the distribution of the extracted on-current (ION) from the measured transfer characteristics of 480/20 (μm/μm) IGZO (red) and ITZO (orange) dual-gate TFTs. The IGZO TFTs exhibits a median ION of 54.4 μA, whereas the ITZO dual-gate TFT exhibits a median of 250.4 μA. Although the ION of the ITZO TFT is 5 times larger, the normalized spread of ION to the median over the wafer is double (15.4% for ITZO and 8.8% for IGZO). Threshold voltage is also extracted from the same measurements, yielding 1.16 V (and σVt = 242 mV) for ITZO and 1.77 V (and σVt = 94 mV) for IGZO TFTs. The 480/20 TFT is the largest footprint TFT used in the implemented designs. In Figure 15, microphotos of the (a) ADC and (b) the L = 3 μm CSA are shown.
\nMicrophotos of the (a) ADC and (b) L = 3 μm CSA on flexible substrate.
The schematic of the CSA is shown in the Figure 16(a). The schematic of the operational amplifier (OPAMP) used in the CSA is shown in Figure 16(b). The OPAMP comprises a differential pair and a load that is driven by a two-stage buffer, initiated by a start-up circuit. The driver consists of two diode-connected load inverters as input and output stages. The output stage is driven by a start-up circuit to initialize the operation and provide ~1 loop gain positive feedback bias to the n-type load of the differential amplifier such that gate voltage follows source voltage. A buffer is also included at the output nodes A and B to increase the speed of the amplifier.
\nSchematic of (a) charge sense amplifier (CSA) and (b) the OPAMP schematic using dual-gate self-aligned TFTs used in the CSA in (a).
The experimental results of open-loop experiments of the OPAMP are shown in Figure 17 for dual-gate self-aligned IGZO TFTs of minimum channel length of L = 5 μm. The maximum gain for the 5 μm design is 43.2 dB with a phase margin of 52°. Both parameters are critical for stable closed-loop operation of an OPAMP. The obtained bandwidth (BW) is 1.4 kHz, and gain-bandwidth reaches 205 kHz. These specs are compared to other publications in the state-of-the-art Table 1 using TFTs. The footprint of the CSA is 0.28 mm2 with the capacitors. The footprint of the CSA can be decreased to 0.07 mm2 if 3 μm design is implemented. These footprints will result in a bezel width of 5.5 mm (L = 5 μm) and 1.3 mm (L = 3 μm) [27] for a 50 μm pixel size.
\nExperimental bode plots of the OPAMP using dual-gate self-aligned IGZO technology for L = 5 μm.
Circuit | \nThis work | \n2018 [11] | \n2012 [8] | \n2013 [10] | \n2014 [9] | \n
---|---|---|---|---|---|
Supply (V) | \n15 | \n10.5 | \n5 | \n50 | \n|
Gain (dB) | \n32 | \n~21 | \n18.7 | \n19.2 | \n|
GBW (kHz) | \n140 | \n2 | \n472 | \n100\n*\n\n | \n|
pm (o) | \n53 | \n50\n*\n\n | \nneg | \n46 | \n|
Area (mm2) | \n0.3 | \n\n | \n2.08 | \n— | \n|
Substrate | \nPI | \n\n | PI | \nGlass | \n|
L (μm) | \n5 | \n10 | \n6 | \n10 | \n
In-Ga-Zn-O-TFT differential amplifier comparison.
Estimated.
The successive approximation C-2C architecture is selected as ADC architecture, due to the low power dissipation and the 0.1% uniformity of metal-insulator-metal capacitors across large-area thin-film wafers. The schematic of the ADC is shown in Figure 18. The comparator is the most critical building block of the ADC for speed and accuracy. To improve the accuracy of the comparator, open-loop offset cancelation [28] is used. The response of a L = 5 μm dual-gate self-aligned TFT-based comparator at 10 kHz for two inputs ΔVin = 0 and 10 mV is shown in Figure 19. The offset of the comparator is minimized to less than 10 mV using open-loop cancelation, even though the Vt variation of the TFTs is one order larger.
\nThe implemented SADG TFT ADC block diagram driven with offset compensation.
Measured comparator output with auto-zero offset cancelation for designs using TFTs of minimum L = 5 μm at 10 kHz.
The experimental results of the reconstructed samples from a sinusoidal analog wave applied at the input of the IGZO ADC are shown in Figure 20(a). The IGZO ADC achieves 6-bit resolution at a sampling speed of 133 S/s at 15 V power supply using a L = 20 μm comparator. The clock speed of the IGZO ADC is at 2 kHz matching the bandwidth of the comparator, and 15 clocks are required to complete the conversion. Two options are available to increase the sampling speed of the ADC as set by the specification for 1–2 fps fingerprint readout: channel length downscaling and/or change of TFT technology or change of ADC architecture to flash but then for 6-bit the area might increase dramatically due to the multiple resistors needed and 64 comparators.
\n(a) The applied analog input of 2.061 Hz sinewave signal to the ADC and the reconstructed output points from the digital output of the ADC at a clock frequency of 2 kHz for IGZO and (b) the applied analog input of 15.625 Hz sinewave to the 15 kHz clocked ITZO ADC and the reconstructed output.
The minimum length of the TFTs of the measured ADC is L = 20 μm. The length of the TFT of the comparator of the ADC defines the speed of the circuit. In Figure 19 the response of the L = 5 μm comparator is shown validating 10 kHz operation, 5 times faster compared to the 20 μm comparator used in the ADC. This indicates that 5 μm comparator can increase the sampling speed by 5 times.
\nAnother option to enable a larger increase of the ADC speed is to introduce ITZO TFT for the ADC. ITZO TFT exhibits 5 times larger ION which leads to faster responses [Figure 20(b)]. The ITZO ADC achieves a similar bit resolution of the applied sinusoidal wave at 1 kS/s sampling speed and at 10 V supply voltage. Combining both ITZO and downscaling of the length of the TFTs of the comparator will lead to sampling speeds above 4 kS/s as required for the in-panel readout system of 1 fps. The power dissipation of the ITZO ADC is at 550 μW at 10 V power supply and at 110 μW at 15 V power supply for the IGZO implementation.
\nIn conclusion, TFT-based in-panel analog circuits for 1 fps readout of a fingerprint or palmprints array is presented in this paragraph. The circuit blocks can be integrated side-by-side to the flat panel display with integrated sensor array. Two analog blocks are discussed, being an analog to digital converter and charge sense amplifier. ADCs and CSA downscaling to 5 μm including a 500% ION boost of the ITZO TFTs enable the 4 kS/s operation specifications for the in-panel readout circuits. The use of complementary technologies such as LTPS or LTPO would result an increased performance for important parameters such as the gain-bandwidth and the resolution and speed of the ADC. This will enable a better optimized system for this application.
\nIn this book chapter, we have discussed a roadmap to include additional functionalities on displays by adding a fourth pixel to the display. The purpose of the fourth pixel in this work was a photodetector pixel to realize an in-panel fingerprint or palmprinting function. Several options have been discussed to enable this roadmap. At first, we have elaborated several techniques to realize higher-resolution frontplane (OLED) and TFT backplanes. For the frontplanes, photolitho patterning of the OLED was introduced as a disruptive technology impacting significantly the frontplane resolution. External compensation techniques for the backplane when driving OLEDs are proposed in this book chapter, resulting in a uniform and higher-resolution display by using only 2T1C schemes. As photodetector pixel, we proposed a passive 1 T pixel, with included peripheral circuits to enable a lower system cost.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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\n\nIntechOpen's advisors are professionals and scholars with broad knowledge and understanding of different aspects of the scientific publishing process: editorial, authorship, and reviewing roles; publication ethics, copyright, and general legal issues; as well as bibliographic and technical standards.
\n\nIn order to provide us with unbiased insights, without compromising the privacy of third parties, IntechOpen presents problematic cases to its advisors in an anonymized format.
\n\nIntechOpen publishes books in the English language. If you are interested in the translation of Book Chapters, please check IntechOpen's Translation Policy.
\n\n\n\nIn line with the Principles of Transparency and Best Practice in Scholarly Publishing, you can access a more detailed description of IntechOpen's Advertising Policy.
\n\n\n\nAt IntechOpen we realize that exceptional circumstances can occur, resulting in a request for a refund. We will honor all justified requests in the specific instances outlined in our Refund Policy.
\n\n\n\nAll chapters will be published via IntechOpen's 'Online First' service meaning chapters will be published individually, immediately after review and before the entire book is ready for publication, allowing content to be shared, searched and cited straightaway, thereby generating early stage interest and momentum for your research
\n\nOnline First Chapters are considered published on the day they are posted and are citable from that date.
\n\nChapters will remain listed as Online First until the final versions of the books are published online. Following publication of the full monograph, Chapters will be redirected from the Online First version and will be available only through the final link of the official published page.
\n\nYou are invited to download, use, reproduce, make derivative works of, display, distribute and cite the Online First works. You can find "How to Cite and Reference" by following the link at the end of each online book chapter. Please be aware that it is possible that further editing and changes might be made before the final release of the book.
\n\nIf there are supplemental materials to the chapter, these will be published at the time the final book is published online.
\n\nReaders and Authors can notify us if they find any errors in the works published under Online First. All major errors will be accompanied by a separate correction notice, erratum or corrigendum (Retraction and Correction Policy.)
\n\nIntechOpen books are available online by accessing all published content on a chapter level.
\n\n\n\nIntechOpen publishes different types of publications.
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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). 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