Pushing Pressure Detection Sensitivity to New Limits by Modulus-Tunable Mechanism.

Only microstructures are used to improve the sensitivity of iontronic pressure sensors. By modulating the compressive modulus, a breakthrough in the sensitivity of the iontronic pressure sensor is achieved. Furthermore, it allows for programmatic tailoring of sensor performance according to the requirements of different applications. Such a new strategy pushes the sensitivity up to a record-high of 25 548.24 kPa-1 and expands the linear pressure range from 15 to 127 kPa. Additionally, the sensor demonstrates excellent mechanical stability over 10 000 compression-release cycles. Based on this, a well-controlled robotic hand that precisely tracks the pressure behavior inside a balloon to autonomously regulate the gripping angle is developed. This paves the way for the application of iontronic pressure sensors in precise sensing scenarios.

Overcoming the challenge of potent endogenous interferences in limaprost quantification: An innovative methodology combining differential mobility spectrometry with LC-MS/MS for ultra-high sensitivity, selectivity and significantly enhanced throughput.

Limaprost, an orally administered analogue of prostaglandin E1, possesses potent vasodilatory, antiplatelet, and cytoprotective properties. Due to its extremely low therapeutic doses and exceedingly low plasma concentrations, the pharmacokinetic and bioequivalence studies of limaprost necessitate a highly sensitive quantitative method with a sub-pg/mL level of lower limit of quantification. Moreover, the intensity of endogenous interferences can even exceed the maximum concentration level of limaprost in human plasma, presenting further challenge to the quantification of limaprost. As a result, existing methods have not yet met the necessary level of sensitivity, selectivity, and throughput needed for the quantitative analysis of limaprost in pharmacokinetic and bioequivalence investigations. This study presents a new methodology that combines differential mobility spectrometry (DMS) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and utilizes a distinctive strategy to achieve more accurate DMS conditions. This integration yields a method that is currently the most sensitive and features the shortest analytical time, making it the sole technique capable of meeting the requirements for limaprost pharmacokinetic and bioequivalence investigations. This method demonstrates robustness and is successfully employed in a pharmacokinetic investigation of limaprost in human subjects, underscoring that the combination of DMS with LC-MS/MS serves as an efficacious strategy for overcoming the challenges inherent in analyzing biological samples afflicted by multiple interferences.

Ultrasensitive Silicon Photonic Refractive Index Sensor Based on Hybrid Double Slot Subwavelength Grating Microring Resonator.

Silicon photonic-based refractive index sensors are of great value in the detection of gases, biological and chemical substances. Among them, microring resonators are the most promising due to their compact size and narrow Lorentzian-shaped spectrum. The electric field in a subwavelength grating waveguide (SWG) is essentially confined in the low-refractive index dielectric, favoring enhanced analyte-photon interactions, which represents higher sensitivity. However, it is very challenging to further significantly improve the sensitivity of SWG ring resonator refractive index sensors. Here, a hybrid waveguide blocks double slot subwavelength grating microring resonator (HDSSWG-MRR) refractive index sensor operating in a water refractive index environment is proposed. By designing a new waveguide structure, a sensitivity of up to 1005 nm/RIU has been achieved, which is 182 nm/RIU higher than the currently highest sensitivity silicon photonic micro ring refractive index sensor. Meanwhile, utilizing a unique waveguide structure, a Q of 22,429 was achieved and a low limit of detection of 6.86 × 10-5 RIU was calculated.

Impact of the new ultra-high sensitivity mode in a long axial field-of-view PET/CT.

OBJECTIVE: Long axial field-of-view (LAFOV) PET/CT showed improved performance resulting from higher sensitivity. The aim was to quantify the impact of using the full acceptance angle (UHS) in image reconstructions with the Biograph Vision Quadra LAFOV PET/CT (Siemens Healthineers) compared to the limited acceptance angle (high sensitivity mode, HS). METHODS: 38 oncological patients examined on a LAFOV Biograph Vision Quadra PET/CT were analysed. 15 patients underwent [18F]FDG-PET/CT, 15 patients underwent [18F]PSMA-1007 PET/CT, and 8 patients underwent [68Ga]Ga-DOTA-TOC PET/CT. Signal-to-noise ratio (SNR) and standardised uptake values (SUVmean/max/peak) were used to compare UHS and HS with different acquisition times. RESULTS: The SNR was significantly higher for UHS compared to HS over all acquisition times (SNR UHS/HS [18F]FDG: 1.35 ± 0.02, p < 0.001; [18F]PSMA-1007: 1.25 ± 0.02, p < 0.001; [68Ga]Ga-DOTA-TOC: 1.29 ± 0.02, p < 0.001). CONCLUSION: UHS showed significantly higher SNR opening the possibility of halving short acquisition times. This is of advantage in further reduction of whole-body PET/CT acquisition.

Doubly resonant sub-ppt photoacoustic gas detection with eight decades dynamic range.

Photoacoustic spectroscopy (PAS) based gas sensors with high sensitivity, wide dynamic range, low cost, and small footprint are desirable in energy, environment, safety, and public health. However, most works have focused on either acoustic resonator to enhance acoustic wave or optical resonator to enhance optical wave. Herein, we develop a gas sensor based on doubly resonant PAS in which the acoustic and optical waves are simultaneously enhanced using combined optical and acoustic resonators in a centimeter-long configuration. Not only the lower detection limit is enhanced by the double standing waves, but also the upper detection limit is expanded due to the short resonators. As an example, we developed a sensor by detecting acetylene (C2H2), achieving a noise equivalent absorption of 5.7 × 10-13 cm-1 and a dynamic range of eight orders. Compared to the state-of-the-art PAS gas sensors, the developed sensor achieves a record sensitivity and dynamic range.

Ultra-high sensitivity cardiac troponin-I concentration and left ventricular structure and function in women with ischemia and no obstructive coronary artery disease.

Aims: Women are disproportionally impacted by ischemia and no obstructive coronary artery disease (INOCA), and such women are at increased risk of developing heart failure with preserved ejection fraction (HFpEF), however the mechanisms linking these conditions remain poorly understood. The aim of this study was to determine whether ultra-high sensitivity cardiac troponin I (u-hscTnI), an indicator of cardiomyocyte injury, is associated with abnormalities in myocardial perfusion and left ventricular (LV) structure and function in women with INOCA. Methods: 327 women with INOCA enrolled in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study underwent vasodilator stress cardiac magnetic resonance imaging (CMRI) and u-hscTnI measurements (Simoa HD-1 Analyzer, Quanterix Corporation). Multivariable linear regression was used to evaluate associations between u-hscTnI concentrations and myocardial perfusion (MPRI), LV mass index and feature-tracking derived strain measures of LV function. Results: u-hscTnI concentrations were quantifiable in 100% of the cohort and ranged from 0.004 to 79.6 pg/mL. In adjusted models, u-hscTnI was associated with LV mass index (+2.03; 95% CI 1.17, 2.89; p < 0.01) and early diastolic radial strain rate (SR) (+0.13; 95% CI 0.01, 0.25; p = 0.03), early diastolic circumferential SR (-0.04; 95% CI -0.08, 0.002; p = 0.06) and early diastolic longitudinal SR (-0.03; 95% CI -0.07, 0.002; p = 0.06). u-hscTnI was not associated with MPRI (p = 0.39) in adjusted models. Conclusion: Together, these findings support cardiomyocyte injury as a putative pathway towards adverse LV remodeling and dysfunction; however, further research is needed to define the specific mechanism(s) driving myocellular injury in INOCA.

Clinical usefulness of a novel high-sensitivity hepatitis B core-related antigen assay to determine the initiation of treatment for HBV reactivation.

BACKGROUNDS: A fully automated, novel, high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developing. The purpose of this study is to evaluate the efficacy of measuring HBcrAg, using that assay, to diagnose HBV reactivation in a multi-center setting, compared with ultra-high-sensitivity HBsAg (iTACT-HBsAg) and HBV DNA assays. METHODS: Forty-four patients with HBV reactivation from 2008 to 2020 were enrolled in four hospitals. Serial serum specimens from the patients were assessed retrospectively for their HBcrAg levels by iTACT-HBcrAg (lower limit of detection; 2.0 log U/mL) and HBsAg levels by iTACT-HBsAg (lower limit of detection; 0.0005 IU/mL); these were compared to the HBV DNA levels. HBV reactivation was defined as detection of serum HBV DNA, including unquantifiable detection. RESULTS: At HBV reactivation and/or thereafter, HBV DNA levels were quantified (≥ 1.3 log IU/mL) in the sera of 27 patients, and were below the level of quantification (< 1.3 log IU/mL) in the sera of 17 patients. Of the 27 patients with HBV reactivation and whose serum HBV DNA was quantified, the sera of 26 and 24 patients (96.3% and 88.9%) were positive by iTACT-HBcrAg and iTACT-HBsAg, respectively. HBcrAg was detectable by iTACT-HBcrAg before HBV DNA was quantifiable in 15 of the 27 patients. Of the 11 patients with HBV reactivation and undetectable HBcrAg by iTACT-HBcrAg at HBV reactivation and/or thereafter, 10 had unquantifiable HBV DNA and none developed HBV reactivation-related hepatitis. CONCLUSIONS: The iTACT-HBcrAg assay is useful for monitoring HBV reactivation to determine the initiation of treatment with nucleos(t)ide analogues.

Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma.

BACKGROUND & AIMS: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. METHODS: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). CONCLUSIONS: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. CLINICAL TRIAL NUMBER: UMIN000001299. LAY SUMMARY: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.

Suspended CNT-Based FET sensor for ultrasensitive and label-free detection of DNA hybridization.

A suspended carbon nanotube (SCNT)-based field effective transistor (SCNT-FET), which was fabricated by utilizing the surface tension of liquid silver to suspend a CNT between two Pd electrodes, was proposed for the detection of DNA hybridization. Benefits from the separation between the CNT and the substrates could be observed; namely, the conductivity of a SCNT-FET was much higher (two orders of magnitude) than that of a FET based on an unsuspended CNT and about 50% sensing surface of CNT was freed from substrate. The Slater-Koster tight-binding method was adopted for geometry optimization and transport property calculation of the SCNT bound with DNA. The result showed that the conductance (G = 1/R) of the SCNT decreased in order with the binding of single-stranded DNA (SSDNA, probe DNA) and double-stranded DNA (DSDNA) and that the ability of DSDNA to weaken the conductivity of the SCNT was several times higher than that of SSDNA. SEM and Raman spectroscopy were used to demonstrate that DNA could be bound successfully onto the SCNT using a 1-pyrenebutanoic acid succinimidyl ester (PBASE) as a linkage. Ultra-high sensitivity detection of DNA [with a limit of detection (LOD) as low as 10 aM] was obtained using such an SCNT-FET, which showed a lower value than that of a previously reported FET DNA biosensor whose sensing materials were in direct contact with the substrate.

Quantitative nanoimmunosensor based on dark-field illumination with enhanced sensitivity and on-off switching using scattering signals.

A nanoimmunosensor based on wavelength-dependent dark-field illumination with enhanced sensitivity was used to detect a disease-related protein molecule at zeptomolar (zM) concentrations. The assay platform of 100-nm gold nanospots could be selectively acquired using the wavelength-dependence of enhanced scattering signals from antibody-conjugated plasmonic silver nanoparticles (NPs) with on-off switching using optical filters. Detection of human thyroid-stimulating hormone (hTSH) at a sensitivity of 100 zM, which corresponds to 1-2 molecules per gold spot, was possible within a linear range of 100 zM-100 fM (R=0.9968). A significantly enhanced sensitivity (~4-fold) was achieved with enhanced dark-field illumination compared to using a total internal reflection fluorescence immunosensor. Immunoreactions were confirmed via optical axial-slicing based on the spectral characteristics of two plasmonic NPs. This method of using wavelength-dependent dark-field illumination had an enhanced sensitivity and a wide, linear dynamic range of 100 zM-100 fM, and was an effective tool for quantitatively detecting a single molecule on a nanobiochip for molecular diagnostics.