Experimental results without PCM.
\r\n\t2) The divergence between the levels of reliability required (twelve-9’s are not uncommon requirements) and the ability to identify or test failure modes that are increasingly unknown and unknowable
\r\n\t3) The divergence between the vulnerability of critical systems and the amount of damage that an individual ‘bad actor’ is able to inflict.
\r\n\t
\r\n\tThe book examines pioneering work to address these challenges and to ensure the timely arrival of antifragile critical systems into a world that currently sees humanity at the edge of a precipice.
Cardiovascular diseases (CVDs) are the major causes of premature death and chronic disability worldwide [1]. Among CVD-related deaths, the occurrence of inherited lethal arrhythmias is the main reason for sudden cardiac death (SCD) in cardiac patients especially at young age [2]. Although many risk factors associated with SCD have been identified and understanding of pathogenesis of many cardiac diseases is progressing, the considerable number of cardiac patients still suffers SCD without warning, and we are still far from disease-specific treatment. Heterogeneous and multifactorial natures of genetic cardiac diseases are reasons for these complications. Furthermore, founder mutations causing cardiac disease have been reported in Finland [3], the Netherlands [4], and South Africa [5]. Not only disease phenotypes vary among different mutations, but also these vary among individuals carrying the same mutation. For example, long QT syndrome (LQTS) patients demonstrate a wide range of clinical phenotypes even among family members with the identical mutation [6]. Despite carrying the same gene variant resulting in cardiac disease, patients often demonstrate the wide spectrum of clinical outcomes ranging from the absence of distinct electrocardiogram (ECG) abnormalities and being lifelong asymptomatic to clear abnormalities in ECG (e.g., prolonged QT interval and arrhythmias) and premature SCD. In addition, SCD could also be the first manifestation of cardiac disease. These suggest that the type of genetic mutation cannot always be the sole factor that dictates the prognosis of disease and clinical phenotype in all individuals who carry it [7]. Thus, genetic cardiac diseases exhibit the incomplete penetrance and differ among genetic cardiac diseases. For example, Brugada syndrome (BrS) has a penetration range from 12.5 to 50%; mean penetrance of LQTS is ~40%, while overall penetrance of catecholaminergic polymorphic ventricular tachycardia (CPVT) is 78% [7]. Another convoluting factor that hinders the genotype-phenotype correlation is variable expressivity within one phenotype because some mutation carriers display all the phenotypic symptoms, whereas some only display part of mutation-specific phenotypes [8]. The clinical heterogeneity of genetic cardiac diseases suggests that ultimate disease severity (i.e., penetrance and expressivity) does not solely depend on one particular gene causing cardiac disease, but instead results from the combination of many modifying factors such as age, gender, and environmental and lifestyle factors, which either exacerbate or protect against disease [9]. In addition, patients carrying more than one disease-causing mutations (i.e., not polymorphisms) either in the same gene or different genes yield to more severe clinical disease including earlier onset of disease, early heart failure, and premature SCD [10]. Besides these, some of the cardiac diseases overlap their phenotypes with other cardiac diseases (Figure 1). For example, mutations in cardiac sodium (Na+) channel gene, SCN5A, are associated with type 3 long QT (LQT3), BrS, cardiac conduction diseases, and sinus node dysfunction [11]. These incomplete penetrance, variable expressivity, and phenotypic overlap impede the complete understanding of diseases’ mechanism as well as disease-specific treatment. Furthermore, the treatment therapies are mainly targeted for symptomatic patients to prevent and counteract the symptoms, but treatments in asymptomatic individuals are still of concern with variable opinions. Nevertheless, pharmacological therapies have been resulted in poor outcomes in the cardiac diseases [12]. So far, implantable cardioverter-defibrillator (ICD) is the only proven therapy for preventing detrimental consequences in cardiac patients with high risk of SCD [13]. However, ICD implantation is associated with its own complications and lower quality of life [14]. There are large groups of asymptomatic cardiac patients who do not have risk factors, which shift them into high-risk category as candidate for ICD implantation, but suffer SCD. Thus, the management for asymptomatic patients carrying pathogenic variant is the most challenging since SCD could be the first manifestation of disease [15, 16]. The clinical management of most cardiac diseases is suboptimal due to lack of comprehensive knowledge of mutations and possible mechanism involved. Thus, the mechanism of how mutation leads to modify the normal cardiac physiology and engender lethal arrhythmias should be deciphered so that the promising prevention and treatment could be established.
Heterogeneity of genetic cardiac diseases. (A) Overlapping genes causing channelopathies [27]. Brugada syndrome (BrS), long QT syndrome (LQTS), short QT syndrome (SQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) (ref). (B) Overlapping genes causing cardiomyopathies [72]. Arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), left ventricular non-compaction cardiomyopathy (LVNC).
The prior cardiovascular research and drug screening have mostly been performed in animal models through knock-in/knock-out approaches. Although animal models have provided some fundamental information and led to many discoveries in genetic cardiac disease, physiological and pharmacological results cannot directly extrapolate from animals to humans because of some fundamental differences that exist between animal and human cardiac physiology [17]. For example, the resting heart rate of human is 75 bpm, while that of rat is 300 bpm, and the animal (mice and rats) can tolerate 6–400-fold higher concentration of some drugs compared to human [18]. The animal models become even worse when studying human cardiomyopathies due to mutations in contractile proteins, which are not highly expressed in mouse or rat. Therefore, it is more complicated to extrapolate physiological and pharmacological results from animal to human [17, 18]. Furthermore, most of cardiovascular drug screening and toxicology studies were performed in non-cardiac cell lines or animals, which do not accurately represent human CMs. Thus, considerable amount of cardiovascular drugs were withdrawn from market due to off-target effects [19]. Therefore, human tissues are required to study the human cardiac diseases and drug testing. However, the human sample exhibits some of the major challenges: there is limited supply of human cardiac biopsies, and it involves complex procedures and ethical issues. In addition, these cardiac biopsies are typically obtained from the end stage of cardiac diseases; hence it is not possible to understand the mechanism of cardiac diseases [20, 21]. These obstacles are mostly overcome by the groundbreaking discovery of reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) [22, 23] which can be differentiated into cardiomyocytes (CMs) (hiPSC-CMs) [24, 25, 26]. The main advantages of hiPSC-CMs are iPSCs can be generated at any period of a patient’s life, they have unlimited supply, and these retain the same genetic information as the donor, i.e., hiPSC-CMs are patient specific (Figure 2). These are superior features of hiPSC-CMs to the conventional in vitro modeling of cardiac diseases. In addition, hiPSC-CMs can be cultured for several months, which enable us to study acute and chronic effect of mutation and drugs on CMs. Thus, hiPSC-CMs not only provide the platform to investigate the mutation-specific mechanism but also assist to anticipate drug response on an individual basis and guide us to personalized medicine in future.
hiPSC-CM-based modeling of human genetic cardiac diseases. Human-induced pluripotent stem cells (hiPSCs) can be differentiated into hiPSC-derived cardiomyocytes (hiPSC-CMs). There are at least three subtypes of hiPSC-CMs, namely, ventricular-like, atrial-like, and nodal-like hiPSC-CMs. hiPSC-CMs derived from cardiac patients carrying genetic mutation recapitulate calcium and electrical abnormalities (early afterdepolarization (EAD) and delayed afterdepolarization (DAD)). Newly emerging gene editing techniques were able to mitigate these abnormalities in hiPSC-CMs.
Channelopathy cardiac diseases are caused by mutations in cardiac ion channels located in the cellular membrane or organelles. Mutations in ion channels result in misbalance of fine-tuning ion exchange during excitation-contraction coupling (ECC), which could lead to cardiac arrhythmias and SCD in the worst case. The main cardiac channelopathies are CPVT, LQTS, BrS, and short QT syndromes (SQTS) [27]. These cardiac channelopathies have been extensively studied using hiPSC-CMs and described below.
CPVT is an inherited cardiac disease with the prevalence of about 1:5000/10,000. This disease is characterized by premature ventricular contraction and/or polymorphic ventricular tachycardia (VT) induced by adrenergic stimulation in response to emotional stress or physical exercise in structurally normal heart. Over 150 mutations in ryanodine receptor type 2 (RYR2 gene) are responsible for ~ 55% of CPVT type 1 cases (CPVT1), and mutation in calsequestrin 2 (CASQ2 gene) CPVT accounts for 3–5% CPVT type 2 (CPVT2) cases [28, 29]. In addition, mutations in calmodulin (CALM1) genes and in triadin (TRDN) have been reported causing CPVT. RYR2, CASQ2, CALM1, and TRDN are involved in ECC, and mutation in any of these genes results in elevated intracellular Ca2+, which leads to abnormal Ca2+ handling and arrhythmias [28, 29]. In consistency with clinical phenotype, many hiPSC-CM model had demonstrated the exacerbation of electrophysiological and Ca2+ handling abnormalities upon adrenergic stimulation [26, 30, 31, 32]. Furthermore, Zhang and colleagues had modeled hiPSC-CMs harboring CPVT1-associated F2483I mutation in RYR2 gene and demonstrated that CPVT1 hiPSC-CMs had longer and wandering Ca2+ sparks and smaller sarcoplasmic reticulum Ca2+ content [32]. Later on, the same group corrected this mutation using clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) gene editing technique and showed that this mutation is causative rather than associative to the disease [33]. hiPSC-CM model for CPVT has also been used in studying the efficacy of various drugs. Previously we had directly compared the clinical results from CPVT1 patients with dantrolene medication, and the clinical response of dantrolene was similar as in hiPSC-CMs from the same patients; dantrolene abolished or markedly reduced arrhythmias in patients and their hiPSC-CMs with certain mutation in RYR2, while it did not have any clinical effect with hiPSC-CMs or with other RYR2 mutations [31]. Furthermore, an antiarrhythmic drug, flecainide, used to treat CPVT1 patients [34] was able to reduce the Ca2+ irregularities under adrenergic stimulation in CPVT1 hiPSC-CMs [30, 35]. CPVT2 patients harboring homozygous CASQ2-G112 + 5X mutation in CASQ2 gene showed the rapid polymorphic VT under exercise stress test [36]. Adult rat ventricular myocytes were studied to understand the effect of CASQ2 mutation in ECC, demonstrating that mutated CMs exhibited spontaneous extrasystolic Ca2+ elevations and delayed afterdepolarization (DADs) upon adrenergic stimulation [36]. Later, hiPSC-CM model harboring CASQ2-G112 + 5X mutation emulated these phenotypic features of disease, and AAV9-based gene delivery effectively prevents the development of adrenergic-induced DADs and triggered arrhythmias in CPVT2 hiPSC-CMs [37].
LQT type 1 (LQT1) is caused by loss-of-function mutation in KCNQ1 gene encoding α subunit of potassium (K+) channel mediating slow delayed rectifier K+ current (IKs). LQT1 is responsible for 30–35% of all LQTS cases [38]. LQT1 is characterized by prolongation of QT interval in ECG, which could lead to SCD due to VT, typically torsades de pointes [39]. hiPSC-CMs derived from LQT1 patients faithfully recapitulated the clinical hallmark by showing prolonged action potential duration (APD) which is analogous to QT duration in ECG, and reduced IKs current densities are held responsible for abnormal repolarization [40, 41, 42]. ML277, an IKs activator, increased the IKs amplitude by enhancing the activation of IKs, thus resulting in shortening of APD in LQT1 hiPSC-CMs [40]. In addition, adrenergic stimulation in LQT1 hiPSC-CMs induced the early afterdepolarization (EAD) [42], which is similar to arrhythmias triggered in LQT1 patients by exercise or emotional stress [39]. Clinically, β-blockers were effective in minimizing the risk of cardiac events in LQT1 patients [43]. Similar antiarrhythmic effect of β-blockers has been observed in LQT1 hiPSC-CMs [42]. Furthermore, hypokalemia is the electrolyte disturbance caused by lower K+ level in blood serum, which aggravates the QT prolongation and facilitates the development of hypokalemia-induced torsades de pointes in LQT1 patients [39, 44]. We successfully developed and mimicked these disease phenotypes in LQT1 hiPSC-CMs carrying G589D or IVS7-2A > G mutation in KCNQ1 gene. Additionally, lowering the extracellular K+ concentration prolonged APDs and induced the formation of EADs in LQT1 hiPSC-CMs [45]. Both G589D- and IVS7-2A > G-specific LQT1 hiPSC-CMs displayed longer APD and higher Ca2+ abnormalities in baseline; G589D hiPSC-CMs demonstrated prolonged contraction, while IVS7-2A > G hiPSC-CMs showed impaired relaxation [46] observed in our video image-based software analysis [47].
LQT type 2 (LQT2) is an LQTS subtype, which is caused by loss-of-function mutations in KCNH2 gene also known as human ether-a-go-go-related gene (hERG) encoding K+ channel mediating rapid delayed rectifier K current (IKr). LQT2 is responsible for approximately 25–30% of all LQTS cases [38]. Similar to LQT1, LQT2 patients also exhibit the prolongation of QT interval and torsades de pointes. As in LQT1 hiPSC-CM model, LQT2 hiPSC-CMs also recapitulated clinical phenotypes by displaying longer APD resulted from reduced IKr current densities and enhanced EAD following the adrenergic stimulation [48, 49, 50]. Our early study of LQT2 hiPSC-CMs carrying R176W mutation in KCNH2 gene demonstrated the reduced IKr current densities, prolonged repolarization, and increased arrhythmogenicity although the donor is an asymptomatic carrier [50]. These results are in parallel with clinical findings that LQT2 patients usually display symptoms when heart rate is slow. In addition, this report illustrated that electrophysiological abnormalities can be detected in hiPSC-CMs, although iPSCs are derived from asymptomatic carriers of KCNH2 mutations. The application of IKr blockers (E4031 and sotalol) further prolonged the APD resulting in EADs, whereas Ca2+ channel blocker (nifedipine), IK,ATP channel opener (pinacidil and nicorandil), and IKr channel enhancer (PD-118057) reduced the APD and thus mitigated the formation of EAD in LQT2 hiPSC-CMs [48, 49]. Several novel pharmacological strategies including ICA-105574 (potent IKr activator) [51], chaperone modulator N-[N-(N-acetyl-L-leucyl)-L-leucyl]-L-norleucine (ALLN) [52], LUF7346 (hERG allosteric modulators) [53], as well as application of allele-specific RNA interference approach [54] have been attempts to rescue the LQT phenotype in LQT2 hiPSC-CMs. Correcting the mutation associated with LQT2 not only confirmed that mutation caused IKr reduction and APD prolongation but also suggested that trafficking defect as the pathological mechanism is responsible for the electrophysiological phenotype in LQT2 [51, 55].
LQT type 3 (LQT3) is caused by gain-of-function mutations in SCN5A encoding α subunit of cardiac Na+ channels [56]. The gain-of-function SCN5A mutation results in augmented late or persistent Na+ current (INaL), which leads to prolongation of QT interval in ECG and proarrhythmia. LQT3 is the third most common LQTS accounting for 5–10% of all LQTS cases [56]. LQT3 patients exhibit longer QT duration at slower heart rate, thus LQT3 patients are at higher risk for cardiac events during rest or sleep [57]. LQT3 patients harboring V1763 M mutation in SCN5A [58] R1644H mutation in SCN5A [59] or F1473C mutation in SCN5A and a polymorphism (K897 T) in KCNH2 [60] had prolonged QT interval, and in vitro models using hiPSC-CMs derived from all those LQT3 patients demonstrated prolonged APD resulting in the larger INa,L and altered biophysical properties of Na+ channels [58, 59, 60]. Mexiletine, a Na+ channel inhibitor commonly used in LQT3 therapy, lowered the INa,L and thereby rescued the APD prolongation phenotype [58, 59] and suppressed the occurrence of EAD [59] and also corrected the altered Na+ channel inactivation [60]. Incorporating the biophysics of Na+ channel and pharmacological analysis illustrated that the improper functioning of Na+ channel was responsible for LQT3 phenotypes rather than KCNH2 polymorphism [60]. In addition to LQT3, mutation in SCN5A gene can cause BrS, and mixed phenotypes are often seen, which is also known as the “overlap syndrome.” Loss in function of Na+ channel is often seen in BrS. Liang and co-workers had generated hiPSCs from two BrS patients, one with double missense mutation (R620H and R811H) in SCN5A gene (BrS(p1)) and another with one-base pair deletion mutation in the SCN5A gene (BrS(p2)), and showed that BrS hiPSC-CMs derived from both patients had reduced Na+ current and increased triggered activity and abnormal Ca2+ handling [61]. These phenotypes were alleviated by correcting the mutation by CRISPR/Cas9 in hiPSCs derived from BrS (p2) [61]. Importantly, only BrS hiPSC-CMs harboring BrS-associated SCN5A-1795insD mutation displayed reduced Na+ current and upstroke velocity, but not with three sets of hiPSC-CMs derived from BrS patients who tested negative for mutations in the known BrS-associated genes suggesting the Na+ channel dysfunction may not be prerequisite for BrS [62]. In another study, Na+ current and upstroke velocity were reduced, but not the voltage-dependent inactivation in BrS hiPSC-CMs carrying the mutations R1638X and W156X [63].
LQT type 7 (LQT7) or Andersen-Tawil syndrome (ATS) is a rare inherited cardiac disease associated with mutation in KCNJ2 gene (ATS type 1) encoding inward rectifying K+ channel (Kir2.1) and accounts for ~70% of all ATS cases. However, the genetic cause of the remaining 30% of ATS (ATS type 2) remains unknown. In ATS patients, QT interval prolongation is not common, but prominent U wave and QU interval in ECG could be hallmarks of ATS, and they experienced cardiac arrhythmias including non-sustained VT and torsade de pointes [64]. Kuroda and co-workers generated hiPSCs from ATS patients carrying R218W, R67W, and R218Q mutations in KCNJ2 gene and showed strong arrhythmic events and higher incidence of irregular Ca2+ handling in ATS hiPSC-CMs, but flecainide and KB-R7943 (a reverse-mode Na+/Ca2+ exchanger inhibitor) were able to suppress those events [65].
2.6 LQT type 8 (LQT8) or Timothy syndrome (TS) is a very rare genetic cardiac disease which results from mutation in CACNA1C gene encoding Ca2+ channel (CaV1.2). LQT8 is the most severe type of LQTS, which is characterized by markedly prolonged QT interval, severe ventricular arrhythmia, and multiorgan dysfunction [66]. hiPSC-CMs derived from TS patients recapitulated the disease phenotypes, but roscovitine rescued those abnormalities such as altered Ca2+ channel inactivation, prolonged APD, higher incidences of arrhythmias, and abnormal Ca2+ handling [67].
SQT is a rare inherited cardiac disease characterized by QT internal shortening, which is in contrast to QT prolongation observed in LQTS. SQT is associated with mutations in genes associated with K+ channel or Ca2+ channels [68]. The prevalence of SQT is between 0.02–0.1% and 0.05% in adults and children, respectively [69]. Recently El-Battrawy and co-workers had generated hiPSCs from SQT type 1 patients carrying a mutation (N588K) in KCNH2, and hiPSC-CMs mimicked the clinical phenotype of SQT by showing a shortened APD as a result of increased IKr current densities [70]. In addition, SQT hiPSC-CMs exhibited abnormal Ca2+ transients and rhythmic activities, which are enhanced by carbachol, but quinidine alleviated those carbachol-induced arrhythmias and prolonged the APD [70].
Cardiomyopathies are diseases of cardiac muscle and associated with structural and/or functional abnormalities. The most common genetic cardiomyopathies are hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). These genetic cardiomyopathies have been also extensively studied using hiPSC-CMs [71, 72].
HCM is one of the most common genetic cardiac diseases with an estimate prevalence of 1 in 500. HCM is characterized by unexplained symmetrical or asymmetrical left ventricular hypertrophy. Mutations in sarcomeric proteins account for ~60% of all HCM cases including mutation in β-myosin heavy chain (MYH7), cardiac myosin-binding protein C (MYBPC3), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and tropomyosin (TPM1) [73]. Hypertrophy of myocytes and disarray of sarcomere are the histological hallmarks of HCM seen in cardiac biopsies from HCM patients [74], and these histological phenotypes are also observed in hiPSC-CM model of HCM [25, 75, 76, 77]. In addition, HCM hiPSC-CMs also demonstrated other hallmarks of HCM such as nuclear translocation of nuclear factor of activated T cells (NFAT) [75, 76, 77], elevation of β-myosin/α-myosin ratio, and calcineurin activation [75]. Furthermore, isolated CMs from HCM patients displayed the prolonged APDs, increased Ca2+ current densities, reduced transient outward K+ current densities, abnormal Ca2+ handling, and increased frequency of arrhythmias [21]. These electrophysiological and Ca2+ transient irregularity phenotypes have been faithfully recapitulated in HCM hiPSC-CMs [25, 75, 76, 78]. When HCM tissues carrying a mutation in MYBPC3 gene were compared with donor heart sample, no specific truncated MyBP-C peptides were detected, but the overall level of MyBP-C in myofibrils was significantly reduced [79]. Similar haploinsufficiency results were also shown in HCM hiPSC-CMs with mutation in MYBPC3 gene [25, 80], and gene replacement in HCM hiPSC-CMs partially improves the haploinsufficiency and reduces cellular hypertrophy [80]. Similar to higher myofilament Ca2+ sensitivity observed in isolated cardiac biopsies from HCM with E99K mutation in cardiac actin [81], in vitro model of HCM hiPSC-CMs carrying E99K mutation in cardiac actin demonstrated significantly stronger contraction and increased arrhythmogenic events [82] Furthermore, a study in HCM mice harboring I79N mutation in cTnT resulted in increased cardiac contractility, altered Ca2+ transients, and remodeling of action potential [83]. These phenotypes were faithfully recapitulated by HCM hiPSC-CMs carrying the same I79N mutation in cTnT [84]. These hypercontractility and increased arrhythmogenicity phenotypes were reversed in HCM hiPSC-CMs when the E99K mutation in cardiac actin [82] and I79N mutation in cTnT [84] were corrected using CRISPR/Cas9 gene editing technique. Recently, we have shown that HCM hiPSC-CMs carrying TPM1-Asp175Asn mutation exhibited VT type of arrhythmias [78], and this observation is in line with earlier clinical observation of HCM patients with TPM1-Asp175Asn mutation being at increased risk of fatal arrhythmias [85]. Currently, there is no specific pharmacological therapy for HCM patients, and drugs are prescribed mainly based on symptoms and personal history. However, drug therapy has also resulted in poor outcomes in HCM patients [12]. We reported the similar poor antiarrhythmic efficiency of β-blocker in preventing lethal arrhythmias in HCM hiPSC-CMs [78]. In another HCM report, several environmental factors were investigated with hiPSC-CMs to study their effect on disease progression [77]. They found that endothelin (ET)-1 was able to induce HCM phenotypes such as cellular hypertrophy and myofibrillar disarray in hiPSC-CMs, which are inhibited by ET receptor type A blocker [77]. HCM patients exhibited defects in mitochondrial functions and ultrastructure and abnormal energy metabolism [74]. These structural and functional phenotypes were recapitulated in hiPSC-CMs carrying m.2336 T > C mutation in mitochondrial genome causing HCM [86]. They reported that HCM hiPSC-CMs expressed reduced levels of mitochondrial proteins, ATP/ADP ratio, and mitochondrial membrane potential [86].
DCM is a myocardial disease characterized by ventricular chamber enlargement and systolic dysfunction and progressive heart failure without significant change in ventricular wall thickness. Mutations in >30 genes encoding proteins of cytoskeleton, sarcomere, and nuclear lamina are found in 30–35% of DCM patients [87]. DCM patients with mutations in RBM20, encoding RNA binding motif protein 20 (RBM20), have an early onset of disease phenotype [88]. Isolated CMs from DCM patients carrying mutation in RBM20 displayed elongated and thinner sarcomere structure [88], and such disorganized sarcomeric structure phenotypes were recapitulated in DCM hiPSC-CMs carrying mutation in RBM20 [89, 90]. RBM20 is the main regulator of the heart-specific titin splicing, and N2BA isoform is predominantly expressed in CMs from DCM patient carrying mutation in the RBM20 gene [91]. In vitro model of RBM20 hiPSC-CMs successfully mirrored the altered titin isoform expression (titin isoform switch) [89, 90]. Furthermore, RBM20 hiPSC-CMs showed delayed Ca2+ extrusion and reuptake and more Ca2+ being released during each ECC, which resulted into deficient muscle contraction, the hallmark of cardiac dysfunction of DCM patients [89, 90]. In addition, a three-dimensional engineered heart muscle generated from RBM20 hiPSC-CMs showed an impaired force of contraction, and passive stress was decreased in response to stepwise increase in strain, suggesting higher viscoelasticity caused by mutation in RBM20 [89]. Besides HCM, mutation in cTnT also caused DCM and resulted in shifts in Ca2+ sensitivity and force of contraction [92]. Sun and co-workers generated iPSCs from DCM patients carrying R173W mutation in cTnT and reported that DCM hiPSC-CMs exhibited altered Ca2+ handling, decreased contractility, and abnormal sarcomeric α–actinin distribution [93]. DCM patients with lamin A/C (LMNA) mutations show a highly variable phenotype. Cardiac biopsies from DCM patients harboring LMNA mutations exhibit reduced LMNA in nuclei with nuclear membrane damage such as focal disruption and nuclear pore clustering [94]. Nonsense mutation (R225X) in exon 4 of the LMNA gene causing DCM was associated with accelerated nuclear senescence and apoptosis of DCM hiPSC-CMs under electrical stimulation [95]. In another in vitro modeling of DCM, harboring A285V mutation in desmin (DES) using hiPSC-CMs displayed the pathogenic phenotypes of DCM such as diffuse abnormal DES aggregation, poor co-localization of DES with cTnT, and Z-disk streaming with accumulation of granulofilamentous materials or pleomorphic dense structures adjacent to the Z-disk or between the myofibrils [96]. DCM patients harboring R14del mutation in phospholamban (PLN) result in ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias [97]. Similarly, hiPSC-CMs carrying R14del mutation in PLN induced the Ca2+ handling abnormalities, irregular electrical activity, and abnormal intracellular distribution of PLN in DCM hiPSC-CMs [98]. These PLN R14del-associated disease phenotypes were mitigated upon correction of PLN R14del mutation by transcription activator-like effector nuclease (TALENs) gene editing technique [98]. Furthermore, genetic correction of PLN R14del mutation by TALENs improved the force development and restored the contractile function in three-dimensional human engineered cardiac tissue derived from R14del-iPSCs [99].
ARVC is rare genetic cardiac disease with the prevalence ranging from 1:000 to 1:5000 worldwide. The histopathological hallmark of ARVC is the substitution of the cardiac myocytes with fibro-fatty deposits, particularly within the free wall of the right ventricle. The consequent results from the disruption of normal myocardial architecture can lead to right ventricular dysfunction, life-threatening arrhythmias, and SCD [100]. ARVC is caused by mutations in genes encoding desmosomal proteins such as plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmocollin-2 (DSC2) [100]. Similar to immunohistological results from the biopsy sample from ARVC patients [101], ARVC hiPSC-CMs harboring a plakophilin 2 (PKP2) gene mutation mimicked the reduced PKP2 immunosignal [102, 103]. In addition, clusters of lipid droplets accumulating within the cytoplasm were identified in ARVC-hiPSC-CMs associated with structural distortion of desmosomes [103]. Another study showed that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor gamma (PPARγ) activation underlie the pathogenesis of ARVC [104]. It has been observed that male ARVC patients develop earlier and more severe phenotype than female ARVC patients [105]. To understand whether sex hormones in serum may contribute to the major arrhythmic cardiovascular events in ARVC, Akdis and co-workers combined a clinical study and in vitro hiPSC-CM model and showed that increased levels of testosterone accelerate ARVC pathologies, while premenopausal female estradiol levels slow down exaggerated apoptosis and lipid accumulation in ARVC hiPSC-CMs [106].
The reprogramming of somatic cells into pluripotent stems cells and subsequent differentiation into specific cell types is a newly emerging technique and is certainly not free from limitation.
One of the most questionable issues of hiPSC-CMs is their maturity. Despite expressing relevant ion channels [107] and structural genes [25, 26, 75, 76, 89, 108], hiPSC-CMs lack t-tubules and exhibit lower expression of Kir2.1 and weaker contractility; thus they do not fully resemble adult CMs. In order to improve the maturity of hiPSC-CMs and consequently upgrade the functionality of hiPSC-CMs, various techniques have been investigated in different groups. Three-dimensional construction of engineered heart tissue is a rapidly growing technique for structural and functional maturations of hiPSC-CMs [109], which resulted in higher Na+ current density and upstroke velocity [110], and enhances the metabolic maturation [111] comparable to adult CMs. Furthermore, Shadrin and co-workers introduced the “Cardiopatch” platform for three-dimensional culture and maturation of hiPSC-CMs; this platform produces robust electromechanical coupling, consistent H-zone and I bands, and evidence of t-tubules and M-bands [112].
Another issue of hiPSC-CMs is the purity of differentiated CMs. The CMs differentiated from hiPSCs yield in heterogeneous population of CMs. There are at least three subtypes of CMs such as ventricular, atrial, and nodal CMs; among them the majority (~70%) of CMs are ventricular-like, and only a minority of CMs are atrial-like (~20%) and nodal-like (~10%) [40, 58, 93, 107]. Although many molecular and functional characteristics are shared among these CMs subtypes, they also exhibit their own unique features. For example, ventricular CMs have prominent plateau phase (phase 2) in action potential profile, atrial CMs exclusively exhibit IKur channels, and nodal CMs lack strong upstroke velocity [113]. Most of the published methods of differentiation protocol yield in a lower amount of atrial-like and nodal-like CMs [40, 58, 93, 107], but sufficient numbers of subtype-specific CMs are needed to understand the subtype-related disease mechanism and development of specific therapeutic approaches. Atrial fibrillation (AF) is one of the most common cardiac arrhythmias; however, current antiarrhythmic drugs for treatment of AF are not atrial-specific and could cause unacceptable ventricular events [114]. Thus, sufficient supply of atrial CMs is crucial for investigating the AF cellular mechanism. hiPSCs have been differentiated into high-purity atrial-specific CMs by using retinoic acid signaling at the mesoderm stage of development [115]. These patient-specific atrial CMs allow us to investigate in detail mechanisms of AF and to develop atrial-specific therapeutic drugs. Furthermore, sinoatrial node (SAN) dysfunction can manifest bradycardia and asystolic pauses, but its pathophysiology is not completely understood [116]. SAN pacemaker cells from hiPSCs would facilitate the study of the disease mechanism and provide a cell source for developing a biological pacemaker. Protze and co-workers had reported the transgene-independent method for the generation of pacemaker cells (nodal-like CMs) from human pluripotent stem cells by stage-specific manipulation of developmental signaling pathways [117]. Besides CMs, the heart also consists of many other cell types such as fibroblast, endothelial and vascular smooth muscle cells, and also extracellular matrix. Importantly, the origin of cardiac diseases may not always exclusively originate from CMs, but might involve non-CMs. Thus, incorporating the fibroblasts [118], endothelial cells [119], and vascular smooth muscle cells [120] into CMs from the same hiPSCs could offer new insight of disease mechanism.
The establishment of appropriate control is another challenge in disease modeling using hiPSC-CMs. It is generally argued/suggested that when comparing the results between control and mutated hiPSC-CMs, both should have the same genetic background. This objective is achieved in somehow by using healthy family members as control [58, 93]. However, only ~50% of genome is shared between siblings, and phenotypic difference could result from DNA variants in the rest of genome besides disease-associated mutation [121]. Mutated genes can be corrected with the help of newly growing gene editing technology such as TALENs [98] and CRISPR/Cas9 [33, 51, 84], thus establishing the so-called isogenic lines. This isogenic line would be the most appropriate control for comparison as it differs only in the presence and absence of mutation. Therefore, advance genome engineering will not only provide more reliable control lines but also guide us to understand how mutation modifies the normal functioning of cells. However, for diseased CMs without known mutation, healthy family members or otherwise controls are still the best.
While animal models fail to recapitulate human cardiac disease phenotype properly, hiPSC-CMs have been successful in recapitulating crucial phenotypes of many genetic cardiac diseases in terms of morphology, contractility, Ca2+ handling, ion channel biophysics, cell signaling, and metabolism. Most strikingly, hiPSC-CMs provide the patient-specific platform to study the disease mechanism and drug response individually, which the traditional disease modeling technique would never offer. In addition, cardiac subtype-specific arrhythmias and drug screening could be performed with the help of unlimited supply of hiPSC-CMs; thus chamber-specific treatment modalities could be identified. Certainly, by improving the current weaknesses of hiPSC-CMs and incorporating with new gene editing techniques, complex cardiac disease mechanism could be deciphered, and novel effective treatment therapies could be identified to improve the life of cardiac patients.
We would like to thank funders for our research group: Tekes–Finnish Funding Agency for Innovation, Academy of Finland, and Finnish Cardiovascular Research Foundation.
No conflict of interest.
AF | atrial fibrillation |
ARVC/D | arrhythmogenic right ventricular cardiomyopathy/dysplasia |
APD | action potential duration |
ATS | Andersen-Tawil syndrome |
BrS | Brugada syndrome |
Ca2+ | calcium ion |
CPVT | catecholaminergic polymorphic ventricular tachycardia |
CRISPR | clustered regularly interspaced short palindromic repeats |
cTnT | cardiac troponin T |
CVDs | cardiovascular diseases |
DADs | delayed afterdepolarization |
DCM | dilated cardiomyopathy |
DSC2 | desmocollin-2 |
DSG2 | desmoglein-2 |
DSP | desmoplakin |
EAD | early afterdepolarization |
ECC | excitation-contraction coupling |
ECG | electrocardiogram |
ET | endothelin |
hiPSC-CMs | human-induced pluripotent stem cell-derived cardiomyocytes |
ICD | implantable cardioverter-defibrillator |
iPSCs | induced pluripotent stem cells |
K+ | potassium ion |
LMNA | lamin A/C |
LQTS | long QT syndromes |
MYBPC3 | cardiac myosin-binding protein C |
MYH7 | myosin heavy chain |
Na+ | sodium ion |
PKP2 | plakophilin-2 |
PLN | phospholamban |
SAN | sinoatrial node |
SCD | sudden cardiac death |
SQTS | short QT syndromes |
TALENs | transcription activator-like effector nucleases |
TS | Timothy syndrome |
VT | ventricular tachycardia |
In recent years the energy shortage and water pollution have been rising around the world. With the rapid increase in the level of greenhouse gas emissions, the discovery of alternative sources of energy is increasingly gaining importance for the development of a sustainable world. The rising oil price and environmental regulations have dramatically increased the demand for utilizing alternative power sources [1]. In 2015 WHO and UNICEF reported that around 663 million people still use non-potable drinking water. During the emergency conditions, the need for developing efficient and portable techniques to obtain a clean source of water is paramount. One such method is solar distillation using phase change material.
In the twenty-first century, the impact of energy and water on the socioeconomic development of developed and developing nations is significant [1]. Solar energy is one of many renewable energy sources to obtain stable thermal energy future generations [2]. The process of distillation can be used to get fresh water from brackish or contaminated water. Water is available in different forms, such as seawater, underground water, surface water, and atmospheric water. Clean water is essential for good health. These current conditions serve as a motivational factor for the research conducted, to effectively use Phase Change Material for optimum solar distillation to desalinate the water, abundant in situ around Udupi (near the Indian Ocean) [3].
Single/double-slope solar still is a popular solar device used for converting available brackish or wastewater into potable water. Solar still absorbs the thermal energy solar radiation to distillate polluted water into potable water in an enclosed space—still. The principles of heat transfer and energy balance were the governing equations for the operation of single-slope solar still. Because of its lower productivity, it is not popularly used. Numbers of works are undertaken to improve the productivity and efficiency of the solar still [2, 4].
Several PCMs melt and solidify at an array of temperatures, thus creating a focus on various possible applications. These PCMs are applied for numerous thermal storage systems utilizing latent heat, applications in heat pumps, engineering using solar radiation, and space travel. PCMs have been used for heating and cooling for many years, and the study in this regard has been attracting attention since the past decade. The pragmatic results reckoned in the field of water distillation process with the help of solar energy in the presence of energy storage materials like water and MOFs [2, 5].
Solar still is a latent heat storage system, which uses phase change materials (PCMs). Using PCM is an impactful way of storing thermal energy and has benefits in terms of high-energy storage density and the isothermal nature of the storage process. PCMs have been widely used in latent heat thermal-storage systems for heat pumps, solar engineering, and spacecraft thermal control applications. There are large numbers of PCMs that melt and solidify at a wide range of temperatures, making them attractive in a number of applications [6].
The desalination can provide a 24-hour supply of heat and water in greenhouse-based agricultural projects [7]. In another unsteady state modeling and simulation approach, El-Sebaii and his co-authors presented the transient mathematical models for a single-slope single-basin solar still with and without phase change material under the basin liner [3, 8]. They used stearic acid as PCM and used a computer-based simulation procedure to obtain a better insight of temperatures of the still elements and the PCM. The data were correlated using summer and winter day’s temperature data in Jeddah, Saudi Arabia. It was observed that during phase change (liquid to stable) of PCM, the convective heat transfer coefficient from the basin liner to basin water is doubled; thus, the evaporative heat transfer coefficient is increased by 27% upon using 3.3-cm layer of stearic acid beneath the basin liner. Dashtban [9] used paraffin wax as PCM in their theoretical study of PCM-based weir-type cascade solar still. It was expected to obtain enhanced productivity by using PCM, which helps in keeping the temperature of basin high enough to produce the distilled water without interruption, especially after sunset [10]. In this study, water desalination and hot water production using solar still involving PCM are theoretically investigated. The numerical approach is presented to study the performance of desalination units—with and—without phase change materials. The effect of the PCM on the productivity expressed as the amount of water produced is theoretically studied. The following parameters and their effects were theoretically investigated: the type of the PCM, melting point of PCM, solar irradiation. It is hoped to determine the optimum parameter that will result in higher unit productivity. The purpose of a solar distillation system is to clean or purify water within the permissible limit [11, 12]. Besides the problem of water shortage, process energy constitutes another problem area. Due to the high cost of conventional energy sources, which are also environmentally harmful, renewable energy sources have gained more attraction since their use in distillation plants will save conventional energy for other applications, reduce environmental pollution and provide a free, continuous, and low maintenance energy source [13].
The objective of this thesis is to study how solar distillation is used by nature to produce rain, which is the primary source of freshwater supply and replicate the process using knowledge of engineering. Solar radiation falling on the surface of the sea is absorbed as heat and causes evaporation of the water. The vapor rises above the surface and is moved by winds [7]. When this vapor cools down to its dew point, condensation occurs, and freshwater precipitates as rain. All available artificial distillation systems are small-scale duplications of this natural process.
Solar distillation differs from other forms of desalination that are more energy-intensive, such as methods such as reverse osmosis, or simply boiling water due to its use of free energy. A very common and, by far, the most significant example of solar distillation is the natural water cycle that the Earth experiences [4].
The novelty of the present study is an in-depth and multifaceted comparison of two solar distillation methods, that is, one utilizing PCM to discover an effective way to bring about solar distillation and another technique reflecting the natural phenomenon of distillation. Two methods can accompany the distillation of water using solar energy. The first method utilizes the so-called greenhouse effect to evaporate saltwater enclosed in a simple solar still (direct collection). A typical basin type containing the saline water is covered with a transparent airtight top. The top is mounted sloping downward toward sweet water collecting troughs. Solar energy is absorbed by the basin, causing the water to evaporate and condense on the inside of the cover and slides down into the collecting trough. The second method or indirect collection system often involves more than one subsystem, one for collecting and another for energy storage and the third system for energy utilization in the distillation process, multi-stage flash evaporation mar offer good potential when utilized in a solar distillation system [6].
To emphasize the scope of this research, consider rural areas in and around Udupi district and several such underdeveloped regions around the tropic of cancer. In these areas, the solar distillation process yields drinking water tantamount to the process of rain generation in the water cycle. The solar radiation causes water to evaporate, segregating the water vapor from salt or impurities. The vapor formed from the process of evaporation condenses on the still for collection [14]. The fundamental operation is evaporation. As the temperature of water increases, vaporization starts at the surface of the liquid. The vapor then rises from the surface of the water and gets condensed on the top cover. The condensed vapor is free from minerals and impurities and thus separated through some distillate channel [15]. The application of finding from this thesis encompasses solar energy applications, primarily supported by government initiatives in the countries along tropic of cancer, including India, Mexico, and UAE.
We are choosing two heights—5 and 7 cm— of PCM to understand and relate this distillation over real application in salt pans. The average height of human-made salt pans near the coast of Karnataka is in the range of 25 cm. Since the height of PCM is less than the height of the salt pan, its implementation is possible. If implemented, this method of distillation can obtain not only potable water but also residue salt [16]. The 2-cm increment is to study the effect.
Figure 1 below represents the solar still to be designed as intended, upon which experimental work has been performed to yield the results as presented below. Figure 2 represents the schematic of that implementation. The angle of Glass Cover is kept at 32° following the laws of reflection and refraction, to explain that let us consider Snell’s law of refraction and law of reflection.
Schematic of glass cover and sunrays.
Solar distillation still with PCM: schematic [4].
Figure 1 schematic is a focused view of glass cover in Figure 2, say μ2 = 1.003 and μ1 = 1.517 are refractive indices of air and glass cover [17];
we have,
And so assuming all rays are incoming perpendicular, thus,
we get
which is the ultimate critical angle of the glass cover, and the angle we chose is 32° signifying maximum refraction [4].
Giving as of Figure 1, say we have θ1 = 32° and θ2 = 58°
Figure 3 shows PCM classified according to their commonalities as per the melting point and the enthalpy of fusion. It follows that the two vital characteristics of phase change material, relating to their semantics “phase” and “change,” are derivates of temperature and heat released during the phenomenon of phase change [18, 19].
Classes of materials that can be used as PCM and their typical range of melting temperature and melting enthalpy [15].
In this pragmatic study, the experimental setup is similar to the one described in Figure 1, and the following phase change material was used:
Water and water solutions with eutectic compositions are used below the triple point [5].
Phenol.
As we can observe in Figure 2, both of these compounds are on the left corner of the graph with melting temperature near zero or below zero and enthalpy of fusion around 300 MJ/m3. Hence, the comparison is rather challenging owning to the similarities between the two compounds [20].
As far as the solar distillation goes, the following Figure 4 summarizes the various substances used for an optimized solar distillation setup. Each material novel and being researched upon [14].
Various materials used for solar distillation [3].
Double-slope solar still shown schematically in Figure 5 was used to conduct the experiments [21]. Concerning Figures 1 and 2, we have designed this schematic with lines of varying strokes and measurements of solar still that we implemented for real-time experiments.
Schematic of double-slope solar still measurements in cm.
As shown in Figure 5, the base or basin of double-slope solar still was made using an 18-mm-thick waterproof plywood obtained from a local vendor marking the instance of the in situ experimental setup. The side walls were constructed using the same 6-mm thick plywood. The solar basin had an approximate active area (A) of 0.9 m2. The inside of still was coated with waterproofing M-Seal an epoxy compound with a resin and a hardener. The compound prevents leakage through joints of sidewalls and the base of the still [22].
Since solar radiation has three components for the receiving surface namely, absorption, reflection, or transmission.
To account for these characteristics, we introduce additional properties:
Absorptivity, α, as the fraction of incident radiation absorbed.
Reflectivity, ρ, the fraction of incident radiation reflected.
Transmissivity, τ, the fraction of incident radiation transmitted.
We see, from conservation of energy:
Since the solar still includes opaque surfaces, as we are painted the walls with black,
τ = 0, so that: α + ρ = 1
The basin of the still was also painted black. Owning the height (h) of 0.2 m and area (A) of 0.9 m2 basin has the capacity of
Through the sidewalls, the distillate was collected via streamline channels. In an enclosed basin tank that was subjected to the solar radiation was filled with tap water via the inlet valve. Temperatures of water, glass cover, and water-vapor mixture were noted every hour using thermocouples of k-type, which have an accuracy of ±0.2°C and a least count of
Distillate collected was also measured during temperature recording. Solar intensity falling on solar still was taken from the reading measured by Pyranometer. We had statistical knowledge from SynergyEnvio-Engineerings that around Udupi, Karnataka (Latitude: 13.35, Longitude: 74.75). Annual average of solar irradiation (E) is 5.44 kWh/m2/day.
For approximately 90 bright sunny days in summer, this translates to (90 × 4.895) or 440.55 kWh.
440.55 kWh energy per still, considering a rooftop has room for 10 stills (maximum space needed is 13 m2), this energy is equivalent to 4405.5 kWh [18].
Water was the sole element in the still influencing the heat released and the rate of interphase mass transfer. So we studied the water up to two depths 0.05 and 0.07 m and calculated relevant parameters [20].
The PCM material was evenly distributed and covered by a 5-mm thick metal plate. The sides of the metal plate were sealed using M-Seal chemical to avoid leakage or contact of PCM and water. The same solar distillation experiments were conducted with a fixed amount of different PCM, and the distillate collected was recorded on an hourly basis; 5 kg of phenol as PCM was used to perform the experiments at 0.05 and 0.07 m.
We have used single-basin, double-slope solar distillation still for the study and hence the results have signified the need for multi-slope and multi-basin for improved performance. Observations were made for water temperature (
Tables 1 and 2 describes the variation of water temperature recorded from 8:30 am until 5:30 pm in 9 hours, each with different heights of water—5 and 7 cm respectively. Water and condensing surface temperature are averaged and recorded in a separate column, which is correlated with distillate collected, Figures 6 and 7 show variation of temperatures Tw, Tg, and Tv with increasing time in hours. As the day progresses till noon, the water temperature increases faster as compared to the condensate temperature due to exposure of the glass surface to the ambient atmosphere. Alteration in condensate and water temperature can be attributed to unstable climatic conditions. However, in all cases, the pattern followed by the hourly variation shows a constant rise and fall in all line plots (Figure 8).
S. No. | Time (h) | Tw (°C) | Tg (°C) | Tv (°C) | Distillate (mL) |
---|---|---|---|---|---|
1 | 9 | 30.3 | 28.3 | 30.01 | 0 |
2 | 10 | 39.3 | 32.7 | 36.3 | 23 |
3 | 11 | 45.6 | 37.2 | 421.4 | 106 |
4 | 12 | 52.2 | 44.1 | 47.15 | 204 |
5 | 13 | 54.3 | 52.7 | 52.5 | 287 |
6 | 14 | 56.1 | 53.3 | 55.7 | 348 |
7 | 15 | 55.2 | 48.3 | 53.55 | 273 |
8 | 16 | 49.1 | 45.7 | 48.2 | 217 |
9 | 17 | 48.7 | 38.5 | 42.65 | 149 |
Experimental results without PCM.
Water depth = 0.05 m.
S. No. | Time (h) | Tw (°C) | Tg (°C) | Tv (°C) | Distillate (mL) |
---|---|---|---|---|---|
1 | 9 | 30 | 27.8 | 29.95 | 0 |
2 | 10 | 35.3 | 32.8 | 36 | 5 |
3 | 11 | 41.2 | 37.6 | 41.4 | 9 |
4 | 12 | 48.7 | 43.8 | 48.15 | 109 |
5 | 13 | 51.3 | 47.4 | 53.5 | 201 |
6 | 14 | 54.8 | 50.8 | 54.7 | 330 |
7 | 15 | 52.3 | 45.3 | 52.55 | 292 |
8 | 16 | 48.7 | 39.1 | 47.2 | 215 |
9 | 17 | 45 | 34.2 | 41.65 | 157 |
Experimental results without PCM.
Water depth (d) = 0.07 m.
Hourly variation of temperature at water depth-1.
Hourly variation of distillate yield at water depth-1.
Temperature variation at water depth-2.
It can be inferred from the above implications and Figures 7 and 9 that the yield of distillate and the pattern of rising and falling of the curve is similar indicating no variation upon water depth change. The temperature of the condensing surface temperature is rising since morning till past noon and decreases after maxima. We can notice that the temperature variation of water basin coupled with PCM, as shown in Figures 10 and 11 show similar and broader variation when compared to the curves of water in Figure 8 and 9 [26, 27]. In the early hours of the day, the inner glass temperature is close to that of water basin temperature. However, as the day, progresses the difference broadens because water can absorb some of the incident solar energy, whereas glass transmits most of the incident solar intensity. From figures about PCM phenol, we can see how phenol is retaining the solar energy, which decreases the slope of the line, which indicates declining temperature with an increase in hours.
Hourly variation of distillate yield at water depth-2.
Hourly variation of distillate with phenol as PCM-1.
Hourly variation of distillate yield with phenol as PCM-2.
Five kilograms of phenol was covering the 5-mm metal plate in the solar still basin while the experiment was being conducted, there was no mixing of water and PCM. The reading of these experiments was taken on an hourly basis till 5.00 pm and the cumulative distillate of the next 2 h was taken the next day at 9.00 am [8].
In Figures 12 and 13, it can be seen that the highest temperature attained by the water basin decreases with an increase in depth of water as in the case of PCM with and without PCM too (Tables 1 and 2). However, the standard deviation when Phenol as PCM is comparatively larger (Tables 3 and 4). In Figures 10 and 11, it can also be observed that for phenol, there has been a 4.1% drop in the maximum condensate surface temperature when the water depth has been increased from 5 cm to 7 cm. The decrease in water basin temperature with an increase in depth of water can be attributed to an increase in the volume of water. After sunset, due to a lack of solar radiation, the temperature of water in the basin decreases at a slower rate due to the use of stored heat energy from the PCM. The variation between water basin temperatures in two cases without phenol and with phenol at different water depths is subject to environmental conditions like fluctuation in solar radiation, wind speed, ambient temperature, and spatial wind barriers.
Hourly variation of temperature with phenol-1.
Hourly variation of temperature with phenol-2.
S. No. | Time (h) | Tw (°C) | Tg (°C) | Tv (°C) | Distillate (mL) |
---|---|---|---|---|---|
1 | 9 | 31.8 | 29.5 | 30.35 | 0 |
2 | 10 | 38.6 | 33.5 | 36.05 | 28 |
3 | 11 | 43.8 | 38.4 | 41.1 | 95 |
4 | 12 | 51.6 | 45.6 | 48.6 | 193 |
5 | 13 | 54.7 | 52.1 | 53.4 | 286 |
6 | 14 | 57.1 | 52.5 | 54.8 | 370 |
7 | 15 | 55.4 | 49.6 | 52.5 | 297 |
8 | 16 | 49.5 | 45.1 | 47.3 | 268 |
9 | 17 | 45.2 | 39.8 | 42.5 | 1760 |
10 | 18 + 19 | — | — | — | 84 |
Experimental results with phenol as PCM.
Water depth = 0.05 m.
S. No. | Time (h) | Tw (°C) | Tg (°C) | Tv (°C) | Distillate (mL) |
---|---|---|---|---|---|
1 | 9 | 30.2 | 27.8 | 29 | 0 |
2 | 10 | 35.1 | 32.6 | 33.85 | 5 |
3 | 11 | 42.8 | 37.4 | 39.5 | 8 |
4 | 12 | 47.4 | 44 | 45.7 | 115 |
5 | 13 | 51.6 | 47.7 | 49.65 | 195 |
6 | 14 | 54.6 | 50.7 | 56.78 | 323 |
7 | 15 | 52.2 | 45.3 | 48.75 | 313 |
8 | 16 | 48.6 | 39.2 | 43.9 | 242 |
9 | 17 | 45 | 34.3 | 39.65 | 189 |
Experimental results with phenol as PCM-2.
Water depth = 0.07 m.
The rationale behind conducting this study was to establish a clear relationship between incident solar radiation and the amount of fresh water produced. After developing the relationship and analyzing statistical information, we concur with the results from confirming data with two different depths [28, 29]. Then PCM was introduced, we chose phenol having attributions of economic availability and versatile properties. Phenol was also varied between two heights, and data was contrasted with that of water. Underlying factors were calculated as follows related to the heat and mass transfer [15].
We know from Dunkle [30], the hourly evaporation per m2 from solar still is given by:
where,
C and n are constants.
Also, the heat produced or
which is approximately (Ta − Tw) as basin and water temperature is almost the same, basin being assumed a black body.
Above gives a model to find Q and A for the required basin the fraction Q/A yields the power in kWh/m2.
For a fixed amount of water, the cumulative amount of freshwater produced had a steep rise as the sun goes higher until sunsets (Table 5). PCM, however, continue to heat the water even after the sunset giving the effect of evaporation a boost. We are assuming this as a unit operation under steady-state conditions because we are assuming that the feed water equals the sum of the rate of freshwater produced and the rate of hot water leaving the unit. Accordingly, the productivity of the unit decreases since the vapor pressure decreases. One also can notice (Figure 11) that the rate of production is significant during the day time and gets lower after sunset. The outcome of variation of height is that the amount of distillate collected reduced with the increase in the height of water in the solar still (Figure 14) [31, 32].
S. No. | Height (m) | PCM | Distillate collected (mL) |
---|---|---|---|
1 | 0.05 | No PCM | 1595 |
2 | 0.05 | Phenol | 1788 |
3 | 0.07 | No PCM | 1333 |
4 | 0.07 | Phenol | 1478 |
Cumulative distillate collected results.
Cumulative distillate collected at two heights.
The potential advantages of solar still with PCM (phenol) are numerous, including flexibility, processability, low material cost, and independence on scarce resources. The flexibility as an advantage is shared with solar cells and solar energy storage panels and is a feature allowing the solar stills with PCM to be incorporated into applications where flexibility is an advantage. Such solar stills that can be rolled out onto a roof or other surfaces are one option. Processability is another major selling point of PCM infused solar stills. Both solar stills with and without PCM depend on distillation methods wherein sunrays are concentrated by glass requiring massive amounts of energy; with PCM based solar cells, on the other hand, energy is stored and for distillation, which yields distillate of desalinated water and complete setup are have a possibility of implementation on a larger platform. Flexibility and more energy storage capacity allows for up-scaling the production and thus reducing the cost per area of PCM solar stills. The promise of low material cost and minimal use of scarce materials can be realized with optimized PCM solar stills.
The rationale behind this research work is to apply and analyze the thermal energy engendered by the PCM using the incident solar radiation. The practical work conducted at two water depths concludes the inverse proportionality between the water level and heat released by water; we relate this to the volume occupied by the water in the still. It also follows that, as the water depth decreases, the distance between the top condensing cover and surface of the water also increases, affecting the distillate production.
The cumulative distillate yield at 0.05 m in the double-slope solar still was 1595 mL, and 1788 mL when the experimented with no PCM, phenol as PCM.
The cumulative distillate yield at 0.07 m in the double-slope solar still was 1333 mL, and 1478 mL, when the experimented with no PCM and phenol as PCM,
The effectiveness of PCM to be used to enhance solar distillation intersected with the depth of water in solar still as the efficiency of still changed.
Phenol gave an increase of distillate yield of nearly ~11.5%.
The data available could be used to prepare the theoretical model to predict the performance of solar stills for solar distillation under the climatic condition in the parts of the world (where the intensity of solar irradiation is around 5.44 kWh/m2/day). Efficient and optimized stills and solar distillation systems are projected as replacing wood with carbon fiber or a more effective insulator. As we can observe in the world map, near the tropic of cancer where solar radiation is potent, and seashore is close, solar distillation is a viable option in case of water shortage. Solar stills are subject to further analysis to separate dirt particles and impurities. Stills can also be used in groundwater as well as tap water to improve the quality of water by removing dirt and unwanted particles. In essence, solar distillation would play a vital role in meeting world freshwater supply demands. The data obtained could be used to investigate the scope of solar distillation further. From this investigation, we discovered that for domestic application, double-basin single-slope cascade solar still is a suitable and economical design.
C | constant |
b | average spacing between water and glass surface (m) |
d | the depth of the water (m) |
Gr | Grashoff number (dimensionless) |
A | area of the basin (m2) |
hcw | convective heat transfer coefficient from water surface to glass (W/m2 °C) |
k | thermal conductivity (W/m °C) |
L | latent heat of vaporization (J/kg) |
mw | yield of still per unit area per hour (kg/m2/h) |
Pg | partial vapor pressure at glass temperature (N/m2) |
E | energy of incident radiation |
Pw | partial vapor pressure at water temperature (N/m2) |
Ta | ambient air temperature (°C) |
Tb | basin temperature (°C) |
Tg | average glass temperature (θ°C) |
Tw | average water temperature (°C) |
Tw0 | temperature of basin water (°C) |
UL | overall heat transfer coefficient (W/m2 °C) |
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
",metaTitle:"IntechOpen Women in Science Program",metaDescription:"Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"At IntechOpen, we’re laying the foundations for the future by publishing the best research by women in STEM – Open Access and available to all. Our Women in Science program already includes six books in progress by award-winning women scientists on topics ranging from physics to robotics, medicine to environmental science. Our editors come from all over the globe and include L’Oreal–UNESCO For Women in Science award-winners and National Science Foundation and European Commission grant recipients.
\\n\\nWe aim to publish 100 books in our Women in Science program over the next three years. We are looking for books written, edited, or co-edited by women. Contributing chapters by men are welcome. As always, the quality of the research we publish is paramount.
\\n\\nAll project proposals go through a two-stage peer review process and are selected based on the following criteria:
\\n\\nPlus, we want this project to have an impact beyond scientific circles. We will publicize the research in the Women in Science program for a wider general audience through:
\\n\\nInterested? If you have an idea for an edited volume or a monograph, we’d love to hear from you! Contact Ana Pantar at book.idea@intechopen.com.
\\n\\n“My scientific path has given me the opportunity to work with colleagues all over Europe, including Germany, France, and Norway. Editing the book Graph Theory: Advanced Algorithms and Applications with IntechOpen emphasized for me the importance of providing valuable, Open Access literature to our scientific colleagues around the world. So I am highly enthusiastic about the Women in Science book collection, which will highlight the outstanding accomplishments of women scientists and encourage others to walk the challenging path to becoming a recognized scientist." Beril Sirmacek, TU Delft, The Netherlands
\\n\\nAdvantages of Publishing with IntechOpen
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\n\nWe aim to publish 100 books in our Women in Science program over the next three years. We are looking for books written, edited, or co-edited by women. Contributing chapters by men are welcome. As always, the quality of the research we publish is paramount.
\n\nAll project proposals go through a two-stage peer review process and are selected based on the following criteria:
\n\nPlus, we want this project to have an impact beyond scientific circles. We will publicize the research in the Women in Science program for a wider general audience through:
\n\nInterested? If you have an idea for an edited volume or a monograph, we’d love to hear from you! Contact Ana Pantar at book.idea@intechopen.com.
\n\n“My scientific path has given me the opportunity to work with colleagues all over Europe, including Germany, France, and Norway. Editing the book Graph Theory: Advanced Algorithms and Applications with IntechOpen emphasized for me the importance of providing valuable, Open Access literature to our scientific colleagues around the world. So I am highly enthusiastic about the Women in Science book collection, which will highlight the outstanding accomplishments of women scientists and encourage others to walk the challenging path to becoming a recognized scientist." Beril Sirmacek, TU Delft, The Netherlands
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