Retention-aware zero-shifting technique for Tiki-Taka algorithm-based analog deep learning accelerator.

We present the fabrication of 4 K-scale electrochemical random-access memory (ECRAM) cross-point arrays for analog neural network training accelerator and an electrical characteristic of an 8 × 8 ECRAM array with a 100% yield, showing excellent switching characteristics, low cycle-to-cycle, and device-to-device variations. Leveraging the advances of the ECRAM array, we showcase its efficacy in neural network training using the Tiki-Taka version 2 algorithm (TTv2) tailored for non-ideal analog memory devices. Through an experimental study using ECRAM devices, we investigate the influence of retention characteristics on the training performance of TTv2, revealing that the relative location of the retention convergence point critically determines the available weight range and, consequently, affects the training accuracy. We propose a retention-aware zero-shifting technique designed to optimize neural network training performance, particularly in scenarios involving cross-point devices with limited retention times. This technique ensures robust and efficient analog neural network training despite the practical constraints posed by analog cross-point devices.

Public awareness of advance care planning and hospice palliative care: a nationwide cross-sectional study in Korea.

CONTEXT: Advance care planning (ACP) and hospice palliative care (HPC) have potential benefits for individuals and health systems. Public awareness of them might increase their acceptance. OBJECTIVES: To examine public awareness of ACP and HPC and related factors including individuals' experience of health care among Korean population. METHODS: A cross-sectional study based on a nationally representative sample was conducted. Data from participants aged 15 years or older were examined. Socio-demographic characteristics, health-related factors, health care experience in the past year, and awareness of ACP and HPC were analyzed. Subgroup analysis was conducted to determine associations between specific experiences during outpatient visit and awareness of ACP and HPC. RESULTS: Of a total of 13,546 subjects, 39.3% and 35.7% reported awareness of ACP and HPC, respectively. About half (48.6%) of participants reported that they were completely unaware of ACP or HPC. Recent outpatient visit was positively associated with HPC awareness. Participants were more likely to recognize ACP or HPC if they had experience in hospitalization and health checkup over the past year and had trust in the medical system. Conversely, participants who had inadequate health care access due to cost burden showed low awareness of ACP and HPC. CONCLUSION: There was a lack of public awareness of ACP and HPC. There were significant differences depending on various factors, especially individual health care experiences. Appropriate interventions are needed to facilitate discussion of ACP and HPC, thereby increasing public awareness.

Alignment properties of a ferroelectric nematic liquid crystal on the rubbed substrates.

The orientation characteristics of FNLC-919, a new material with a ferroelectric nematic phase at room temperature, were investigated. Its alignment characteristics varied greatly depending on the relative rubbing direction on both substrates of a liquid crystal cell. In a cell where the two substrates were rubbed in the same direction, they were arranged homogeneously along the rubbing direction without domains or defects in the ferroelectric nematic phase. In a cell where the two substrates were rubbed in the anti-parallel direction, the two domains were twisted in the opposite direction. We quantitatively obtained the twisted direction and angle by matching the experimental data and calculation results using Jones matrix calculations. From the electro-optical experiment, it was confirmed that the polarization direction was opposite to the rubbing direction. In addition, the wavelength and temperature dependence of birefringence was measured for FNLC-919. In a cell where the rubbing direction between two substrates was 90°, two domains of opposite directions were observed in the nematic phase. When it becomes a ferroelectric nematic phase on cooling, the twist is determined to be only in one direction. The twist direction and angle were quantitatively obtained in the nematic and ferroelectric nematic phases. It was twisted more in the ferroelectric nematic phase than in the nematic phase.

Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma.

Peptidyl arginine deiminases (PAD) enzymes have been investigated in various cancers. Recently, PAD enzyme, in particular PAD2, has been further implicated in cancers. Although the expression of PAD2 was significantly higher in hepatocellular carcinoma (HCC) tissue, its diagnostic or prognostic role of PAD2 in HCC patients is unknown. This study investigated whether the expression of PAD2 affects recurrence and survival in HCC patients who underwent hepatic resection. One hundred and twenty-two HCC patients after hepatic resection were enrolled. The median follow-up was 41 months (range 1-213 months) in enrolled patients. To investigate an association between PAD2 expression level and the clinical characteristics of enrolled patients, the recurrence of HCC following surgical resection and survival of the patients were examined. Ninety-eight cases (80.3%) of HCC demonstrated a higher expression of PAD2. The expression of PAD2 was correlated with age, hepatitis B virus positivity, hypertension, and higher alpha-fetoprotein level. There was no association between PAD2 expression and sex, diabetes mellitus, Child-Pugh class, major portal vein invasion, HCC size or number. The recurrence rates in patients with lower PAD2 expression were higher than those with higher PAD2 expression. The cumulative survival rates of patients with higher PAD2 expression were better than those of patients with lower PAD2 expression, but it was not statistically significant. In conclusion, PAD2 expression is closely associated with recurrence of HCC patients following surgical resection.

Anisotropic viscous effects of local flow by a rotating microparticle in nematic liquid crystal.

The presented study opens a perspective to investigate the effects of local flow on nematic liquid crystals. A particle rotated in nematic fluids typically generates a rotationally symmetric local flow, which causes a change in the director orientation. The director above the threshold velocity has a particular angle determined by the ratio of Leslie coefficients, α_{2}/α_{3}. In 5CB liquid crystals, this director angle with respect to the flow is approximately 13^{∘}. The angle is calculated through Ericksen-Leslie theory. The angle is not dependent on rotation frequency or particle size but temperature. The area of the influenced region increases with the rotation frequency and particle size. The changes in radius of the influenced region are calculated theoretically using Ericksen number. Further, an interference pattern appears at the edge of the influenced region by the refractive indexes mismatch between the influenced region and the rest. We experimentally obtain the thickness of the influenced region analyzing intervals of the pattern.

Fiber-Optic Temperature Sensor Using Cholesteric Liquid Crystals on the Optical Fiber Ferrules.

Cholesteric liquid crystals (CLCs) can be applied to various physical and chemical sensors because their alignment structures are changed by external stimuli. Here, we propose a CLC device fabricated by vertically forming the helical axis of the CLC between the cross-sections of two optical fiber ferrules. An optical fiber temperature sensor was successfully implemented using the proposed optical fiber ferrule-based CLC device. A wideband wavelength-swept laser with a center wavelength of 1073 nm and scanning range of 220 nm was used as a light source to measure the variations in the reflection spectrum band according to the temperature change in the CLC cell. The wavelength variation of the reflection spectrum band according to the temperature applied to the CLC cell was reversible and changed linearly with a change in the temperature, and the long-wavelength edge variation rate according to the temperature change was -5.0 nm/°C. Additionally, as the temperature applied to the CLC cell increased, the reflection spectrum bandwidth gradually decreased; the reflection spectrum bandwidth varied at a rate of -1.89 nm/°C. The variations in the refractive indices with temperature were calculated from the band wavelengths of the reflection spectrum. The pitch at each temperature was calculated based on the refractive indices and it gradually decreased as the temperature increased.

Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma.

The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1-213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child-Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection.

Tuning photoluminescence spectra of MoS2 with liquid crystals.

The photoluminescence (PL) and Raman spectra of molybdenum disulfide (MoS2) can be tuned with liquid crystals. A nematic liquid crystal, 5CB, was aligned in a zigzag direction on an MoS2 monolayer flake. The PL and A1g Raman mode peaks of the MoS2 monolayer were shifted by 46 meV and 2 cm-1, respectively, owing to the interaction between MoS2 and the liquid crystal. Based on Lorentzian fitting analysis, it was confirmed that the peak positions and intensity ratios of the trion PL and exciton PL varied with the phase transition of the liquid crystal. This phenomenon was possibly caused by the transfer of electrons from MoS2 to the liquid crystal. This electron transfer varies with the temperature-dependent change in the liquid crystal phase. Therefore, the PL spectra of MoS2 can be tuned simply by controlling the phase, without changing the type of added material.

Cooling Capacity of Transpulmonary Cooling and Cold-Water Immersion After Exercise-Induced Hyperthermia.

CONTEXT: Cold-water immersion (CWI) may not be feasible in some remote settings, prompting the identification of alternative cooling methods as adjunct treatment modalities for exertional heat stroke (EHS). OBJECTIVE: To determine the differences in cooling capacities between CWI and the inhalation of cooled air. DESIGN: Randomized controlled clinical trial. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 12 recreationally active participants (7 men, 5 women; age = 26 ± 4 years, height = 170.6 ± 10.1 cm, mass = 76.0 ± 18.0 kg, body fat = 18.5% ± 9.7%, peak oxygen uptake = 42.7 ± 8.9 mL·kg-1·min-1). INTERVENTION(S): After exercise in a hot environment (40°C and 40% relative humidity), participants were randomized to 3 cooling conditions: cooling during passive rest (PASS; control), CWI, and the Polar Breeze thermal rehabilitation machine (PB) with which participants inspired cooled air (22.2°C ± 1.0°C). MAIN OUTCOME MEASURE(S): Rectal temperature (TREC) and heart rate were continuously measured throughout cooling until TREC reached 38.25°C. RESULTS: Cooling rates during CWI (0.18°C·min-1 ± 0.06°C·min-1) were greater than those during PASS (mean difference [95% CI] of 0.16°C·min-1 [0.13°C·min-1, 0.19°C·min-1]; P < .001) and PB (0.15°C·min-1 [0.12°C·min-1, 0.16°C·min-1]; P < .001). Elapsed time to reach a TREC of 38.25°C was also faster with CWI (9.71 ± 3.30 minutes) than PASS (-58.1 minutes [-77.1, -39.9 minutes]; P < .001) and PB (-46.8 minutes [-65.5, -28.2 minutes]; P < .001). Differences in cooling rates and time to reach a TREC of 38.25°C between PASS and PB were not different (P > .05). CONCLUSIONS: Transpulmonary cooling via cooled-air inhalation did not promote an optimal cooling rate (>0.15°C·min-1) for the successful treatment of EHS. In remote settings where EHS is a risk, access and use of treatment methods via CWI or cold-water dousing are imperative to ensuring survival. TRIAL REGISTRY: ClinicalTrials.gov (NCT0419026).

Bidirectional rotation control of a carbon fiber in nematic liquid crystal using AC electric field.

Colloidal particles dispersed in nematic liquid crystals are aligned along the orientation that minimizes the elastic free energy. Through applying an electric field to a nematic colloidal system, the orientation of the director can change. Consequently, colloidal particles realign to minimize the total free energy, which is the sum of the elastic and electric free energies. Herein, we demonstrate that if the preferred rotation directions given by the electric and elastic free energies are different during realignment, the rotation direction of the particle can be controlled by how we apply the electric field. When the strength of the electric field gradually increases, the particles rotate in the same direction as the rotation of the director. However, when a sufficiently high electric field is suddenly applied, the particles rotate in the opposite direction. In this study, we analyzed the effect of free energy on the bidirectional rotation behavior of the particles using a theoretical model. This study provides an effective approach to control the rotational behavior of colloidal particles over a wide-angle range between two orientational local minima.

Long-term Renal Outcome of Biopsy-proven Acute Tubular Necrosis and Acute Interstitial Nephritis.

BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.

Analogue Orientation Control of a Carbon Fibre in a Nematic Liquid Crystal.

A carbon fibre is a rod-like microstructure, the longitudinal axis of which is aligned with the orientation of the director in a nematic liquid crystal. A nematic liquid crystal with negative dielectric anisotropy is mixed with carbon fibres. By applying an electric field perpendicular to the director, the carbon fibres tend to rotate in response to the electric field, and the directors around the carbon fibres tends to suppress the rotation. We control individual carbon fibres to obtain an expected orientation by handling the competition of two actions. The carbon fibre barely reacts in a small electric field. Meanwhile, when the threshold electric field is exceeded, the carbon fibre rotates with a steep gradient in the direction of the electric field. The change in the rotation shows little hysteresis. As the length of the carbon fibre is increased, the threshold electric field decreases. We analysed the above process with a theoretical model considering the response of the carbon fibre and liquid crystal. This study shows the possibility of accurate analogue orientation control of individual rod-like microstructures.

Combination of Glomerular C4d and Morphologic Glomerular Lesions as a Possible Indicator in the Diagnosis of Acute or Chronic Active Antibody-Mediated Rejection.

BACKGROUND: Linear C4d staining in the peritubular capillaries is considered a sensitive and useful marker of active or chronic active antibody-mediated rejection (ABMR) in transplanted kidneys. However, the diagnostic significance of glomerular C4d deposits (gC4d) is still undetermined. The aim of this study is to evaluate the association of gC4d with clinicopathologic features and to assess its diagnostic value. METHODS: From 2013 to 2018, a total of 158 cases of allograft kidney biopsy specimens were obtained from the Korea University Anam Hospital. The histologic features were evaluated according to the Banff classification. The gC4d were determined through immunohistochemical analyses and classified based on scores of 0 to 3 according to the extent of gC4d. RESULTS: A total of 73 cases (46.2%) showed gC4d, and 37 cases (23.4%), 23 cases (14.6%), and 13 cases (8.2%) were classified with a score of 1+, 2+, and 3+, respectively. The gC4d showed a significant correlation with antibody-associated histologic lesions, including peritubular capillaritis, glomerulitis, and transplant glomerulopathy (P < .001). However, gC4d showed no significant association with cell-mediated injuries such as tubulitis, interstitial inflammation, acute tubular necrosis, and thrombotic microangiopathy. Although positive gC4d alone was associated with nonspecific findings without ABMR, most cases of gC4d combined with glomerulitis or transplant glomerulopathy showed typical histologic features of ABMR, clinically with higher antibody titers and severe functional deterioration. CONCLUSIONS: Glomerular C4d deposits may be an alternate useful marker in the diagnosis of active or chronic active ABMR when combined with histologic features of glomerular lesions.

The role of senescence of bone marrow cells in acute kidney injury.

BACKGROUND: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response. METHODS: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined. RESULTS: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI. CONCLUSION: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.

The influence of family adaptability and cohesion on anxiety and depression of terminally ill cancer patients.

PURPOSE: This study investigated the effect of family members on terminally ill cancer patients by measuring the relationship of the presence of the family caregivers, visiting time by family and friends, and family adaptability and cohesion with patient's anxiety and depression. METHODS: From June, 2016 to March, 2017, 100 terminally ill cancer patients who were admitted to a palliative care unit in Seoul, South Korea, were surveyed, and their medical records were reviewed. The Korean version of the Family Adaptability and Cohesion Evaluation Scales III and Hospital Anxiety-Depression Scale was used. Chi-square and multiple logistic regression analyses were used. RESULTS: The results of the chi-square analysis showed that the presence of family caregivers and family visit times did not have statistically significant effects on anxiety and depression in terminally ill cancer patients. In multiple logistic regression, when adjusted for age, sex, ECOG PS, and the monthly average income, the odds ratios (ORs) of the low family adaptability to anxiety and depression were 2.4 (1.03-5.83) and 5.4 (1.10-26.87), respectively. The OR of low family cohesion for depression was 5.4 (1.10-27.20) when adjusted for age, sex, ECOG PS, and monthly average household income. CONCLUSIONS: A higher family adaptability resulted in a lower degree of anxiety and depression in terminally ill cancer patients. The higher the family cohesion, the lower the degree of depression in the patient. The presence of the family caregiver and the visiting time by family and friends did not affect the patient's anxiety and depression.

Structural characteristics of the brain reward circuit regions in patients with bipolar I disorder: A voxel-based morphometric study.

Bipolar I disorder (BD-I) is often misdiagnosed, leading to inadequate treatment and significant disability along with reduced quality of life. Recent neural models suggest that the reward circuitry is affected in bipolar disorder. The purpose of the present study was to identify structural abnormalities in the brain reward-processing neural circuitry among patients with BD-I. 21 patients with BD-I and 21 healthy controls (HC) participated in this study. Structural magnetic resonance imaging was performed. Region-of-interest (ROI) voxel-based morphometry analysis was applied to assess the presence of structural changes between the BD-I patient group and the control group. The results of the reward circuitry ROI analysis revealed lower gray matter volumes in the left ventromedial prefrontal cortex (VMPFC), left dorsomedial prefrontal cortex (DMPFC), and left ventrolateral prefrontal cortex (VLPFC) in patients with BD-I compared to HC. Our results suggest that abnormalities in the brain reward-processing neural circuitry, especially those in the left VMPFC, left DMPFC, and left VLPFC, may play an important role in the pathophysiology of BD-I.

Secondhand Smoking Is Associated with Poor Mental Health in Korean Adolescents.

In Korea, the prevalence of depression is increasing in adolescents and the most common cause of death of adolescents has been reported as suicide. At a time of increasing predicament of mental health of adolescents, there are few studies on whether secondhand smoking is associated with mental health in adolescents. The objective of this study was to determine whether exposure to secondhand smoke is associated with mental health-related variables, such as depression, stress, and suicide, in Korean adolescents. Data from the eleventh Korea youth risk behavior web-based survey, a nationally representative survey of 62,708 participants (30,964 males and 31,744 females), were analyzed. For students of aged 12 to 18 years, extensive data including secondhand smoking, mental health, sociodemographic variables, and physical health were collected. Chi-square analysis, multiple logistic regression analysis and ordered logistic regression analysis were performed to estimate the association and dose-response relation between secondhand smoking and mental health. Compared with the non-exposed group, the odds ratios (OR) of depression, stress, suicidal ideation, suicidal planning and suicidal attempt in the secondhand smoking exposed group were 1.339, 1.192, 1.303, 1.437 and 1.505, respectively (all P < 0.001). When subjects were classified into two secondhand smoke exposure groups, with increasing secondhand smoking experience, higher was the OR for each mental health related variable, in a dose-response relation. Our findings suggest that secondhand smoking is associated with poor mental health such as depression, stress, and suicide, showing a dose-response relation in Korean adolescents.

Poor-quality sleep is associated with metabolic syndrome in Korean adults.

Sleep disorder and metabolic syndrome (MetS) are important health-related problems. Recently, sleep duration has decreased among Korean adults. In this study, we examined whether sleep quality is associated with MetS by analyzing 301 subjects, aged 20 years or over, without acute and severe illness who visited three primary care clinics. Sleep duration, sleep quality and the risk of sleep-related breathing disorder (SRBD) were assessed with a standardized sleeping-estimating instrument. MetS was defined according to the modified diagnostic criteria of the National Cholesterol Education Program Adult Treatment Panel-III using the Korean abdominal obesity definition. In the multiple logistic regression analysis, compared with the 7-hour sleep group, the adjusted odds ratios (ORs) of the ≤ 5- and ≥ 9-hour sleep groups for MetS were 4.89 and 5.98, respectively. Compared with the good-sleep quality and low-SRBD risk groups, the adjusted ORs of the poor-quality sleep and high-SRBD risk groups were 3.83 and 1.92, respectively (p < 0.05). In the ≤ 5- and ≥ 9-hour sleep groups, the prevalence of elevated triglyceride and high HOMA-IR was higher (p = 0.069). In the poor-quality sleep group, the prevalence of abdominal obesity, elevated triglyceride, low HDL cholesterol, high fasting insulin and high HOMA-IR were higher. In the high-SRBD risk group, the prevalence of abdominal obesity, obesity and elevated triglyceride were higher (p < 0.05). Overall, the ≤ 5- or ≥ 9-hour sleep duration, poor-quality sleep and high-SRBD risk are related with the high prevalence of MetS, perhaps through elevated insulin-resistance resulting from adiposity.

Covalent attachment of biomacromolecules to plasma-patterned and functionalized carbon nanotube-based devices for electrochemical biosensing.

The interface between biomacromolecules and carbon nanotubes (CNTs) is of critical importance in developing effective techniques that provide CNTs with both biomolecular recognition and signal transduction through immobilization. However, the chemical inertness of CNT surfaces poses an obstacle to wider implementation of CNTs in bioanalytical applications. In this paper, we present a review of our recent research activities related to the covalent attachment of biomacromolecules to plasma-patterned and functionalized carbon nanotube films and their application to the fabrication of electrochemical biosensing devices. The SWCNT films were spray-deposited onto a miniaturized three-electrode system on a glass substrate and activated using highly purified atomic oxygen generated in radiofrequency plasma; this introduced oxygen-containing functional groups into the SWCNT surface without fatal loss of the original physicochemical properties of the CNTs. The carboxylated SWCNT electrodes were then selectively modified via amidation or esterification for covalent immobilization of the biomacromolecules. The plasma-treated SWCNT-based sensing electrode had an approximately six times larger effective area than the untreated SWCNT-based electrode, which significantly amplified the amperometric electrochemical signal. Finally, the efficacy of plasma-functionalized SWCNT (pf-SWCNT) as a biointerface was examined by immobilizing glucose oxidase, Legionella pneumophila ( L. pneumophila)-specific antibodies, L. pneumophila-originated DNAs, and thrombin-specific aptamers on the pf-SWCNT-based three-electrode devices. The pf-SWCNT films were found to support direct covalent immobilization of the above-listed biomacromolecules on the films and to thereby overcome the many drawbacks typically associated with simple physisorption. Thus, pf-SWCNT sensing electrodes on which biomacromolecules were covalently immobilized were found to be chemically stable and have a long lifetime.

A fully microfabricated carbon nanotube three-electrode system on glass substrate for miniaturized electrochemical biosensors.

We present an integration process to fabricate single-walled carbon nanotube (SWCNT) three-electrode systems on glass substrate for electrochemical biosensors. Key issues involve optimization of the SWCNT working electrode to achieve high sensitivity, developing an optimal Ag/AgCl reference electrode with good stability, and process development to integrate these electrodes. Multiple spray coatings of the SWCNT film on glass substrate enabled easier integration of the SWCNT film into an electrochemical three-electrode system. O2 plasma etching and subsequent activation of spray-coated SWCNT films were needed to pattern and functionalize the SWCNT working electrode films without serious damage to the SWCNTs, and to remove organic residues. The microfabricated three-electrode systems were characterized by microscopic and spectroscopic techniques, and the electrochemical properties were investigated using cyclic voltammetry and chrono-amperometry. The fully-integrated CNT three-electrode system showed an effective working electrode area about three times larger than its geometric surface area and an improved electrochemical activity for hydrogen peroxide decomposition. Finally, the effectiveness of miniaturized pf-SWCNT electrodes as biointerfaces was examined by applying them to immunosensors to detect Legionella(L) pneumophila, based on a direct sandwich enzyme-linked immunosorbent assay (ELISA) format with 3,3',5,5'-tetramethylbenzidine dihydrochloride/hydrogen peroxide(TMB/H2O2) as the substrate/mediator system. The lower detection limit of the pf-SWCNT-based immunosensors to L. pneumophila is about 1500 times lower than that of the standard ELISA assay.