A novel interdigitated capacitor based biosensor for detection of cardiovascular risk marker

C-reactive protein (CRP) is a potential biomarker whose elevated levels in humans determine cardiovascular disease risk and inflammation. In this study, we have developed a novel capacitive biosensor for detection of CRP-antigen using capacitor with interdigitated gold (GID) electrodes on nanocrystalline diamond (NCD) surface. The NCD surface served as a dielectric layer between the gold electrodes. GID-surface was functionalized by antibodies and the immobilization was confirmed by Fourier transform spectroscopy (FT-IR) and contact angle measurements. The CRP-antigen detection was performed by capacitive/dielectric-constant measurements. The relaxation time and polarizability constants were estimated using Cole-Cole model. Our results showed that the relaxation time constant (tau) of only CRP-antibody was within 10(-16)-10(-13) s, which was increased to 10(-11) s after the incubation with CRP-antigen, suggesting that the CRP-antigen was captured by the antibodies on GID-surface. In addition, polarizability constant(m) of CRP was also increased upon incubation with increasing concentration of CRP-antigen. Our results showed that the response of GID-NCD-based capacitive biosensor for CRP-antigen was dependent on both concentration (25-800 ng/ml) as well as frequency (50-350 MHz). Furthermore, using optimized conditions, the GID-NCD based capacitive biosensor developed in this study can potentially be used for detection of elevated levels of protein risk markers in suspected subjects for early diagnosis of disease

Nanocrystalline diamond film for biosensor applications

In this study, we have developed a novel capacitive biosensor based oil interdigitated gold nanodiamond (GID-NCD) electrode for detection of C-reactive protein (CRP) antigen. CRP is one of the plasma proteins known as acute-phase proteins and its levels rise dramatically during inflammatory processes occurring in the body. It has been reported that CRP in serum can be used for risk assessment of cardiovascular diseases. The antibodies immobilization were confirmed by Fourier transform spectroscopy (FTIR) and contact angle measurements. In this capacitive biosensor, nanocrystalline diamond acting as a dielectric layer between the electrodes. The CRP antigen detection was performed by capacitive/dielectric-constant measurements. Our results showed that the response of NCD-based capacitive-based biosensor for CRP antigen was dependent on both concentration (25-800 ng/ml) as well as frequency (50-350 MHz). Furthermore, using optimized conditions, the biosensors developed in this study can be potentially used for detection of elevated level of risk markers protein in suspected subjects for early diagnosis of disease

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

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

Diamond semiconductor technology for RF device applications

This paper presents a comprehensive review of diamond electronics from the RF perspective. Our aim was to find and present the potential, limitations and current status of diamond semiconductor devices as well as to investigate its suitability for RF device applications. While doing this, we briefly analysed the physics and chemistry of CVD diamond process for a better understanding of the reasons for the technological challenges of diamond material. This leads to Figure of Merit definitions which forms the basis for a technology choice in an RF device/system (such as transceiver or receiver) structure. Based on our literature survey, we concluded that, despite the technological challenges and few mentioned examples, diamond can seriously be considered as a base material for RF electronics, especially RF power circuits, where the important parameters are high speed, high power density, efficient thermal management and low signal loss in high power/frequencies. Simulation and experimental results are highly regarded for the surface acoustic wave (SAW) and field emission (FE) devices which already occupies space in the RF market and are likely to replace their conventional counterparts. Field effect transistors (FETs) are the most promising active devices and extremely high power densities are extracted (up to 30 W/mm). By the surface channel FET approach 81 GHz operation is developed. Bipolar devices are also promising if the deep doping problem can be solved for operation at room temperature. Pressure, thermal, chemical and acceleration sensors have already been demonstrated using micromachining/MEMS approach, but need more experimental results to better exploit thermal, physical/chemical and electronic properties of diamond

A new nanocrystalline diamond-based biosensor for the detection of cardiovascular risk markers

In this paper, a new method to probe associative interactions of C-reactive protein (CRP) antigen with CRP antibody immobilized on a gold-interdigitated diamond electrodes was investigated. The CRP antigen detection was performed by capacitive/dielectric-constant measurements. Our results showed that the dynamic detection range using optimized conditions for a given antibody concentration (100 μg/ml) was found to be in the range 25-800 ng/ml of CRP-antigen. Biosensor developed in this study can be potentially used for detection of elevated CRP levels in suspected subjects for early diagnosis

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders