High Sensitivity Research Articles

Ultrasensitive Detection of Blood-Based Alzheimer's Disease Biomarkers: A Comprehensive SERS-Immunoassay Platform Enhanced by Machine Learning.

Accurate and early disease detection is crucial for improving patient care, but traditional diagnostic methods often fail to identify diseases in their early stages, leading to delayed treatment outcomes. Early diagnosis using blood derivatives as a source for biomarkers is particularly important for managing Alzheimer's disease (AD). This study introduces a novel approach for the precise and ultrasensitive detection of multiple core AD biomarkers (Aβ40, Aβ42, p-tau, and t-tau) using surface-enhanced Raman spectroscopy (SERS) combined with machine-learning algorithms. Our method employs an antibody-immobilized aluminum SERS substrate, which offers high precision, sensitivity, and accuracy. The platform achieves an impressive detection limit in the attomolar (aM) range and spans a wide dynamic range from aM to micromolar (μM) concentrations. This ultrasensitive and specific SERS immunoassay platform shows promise for identifying mild cognitive impairment (MCI), a potential precursor to AD, from blood plasma. Machine-learning algorithms applied to the spectral data enhance the differentiation of MCI from AD and healthy controls, yielding excellent sensitivity and specificity. Our integrated SERS-machine-learning approach, with its interpretability, advances AD research and underscores the effectiveness of a cost-efficient, easy-to-prepare Al-SERS substrate for clinical AD detection.

High specificity and sensitivity of spot urine normetanephrine-to-creatinine ratios in the diagnosis of canine pheochromocytoma.

To evaluate the specificity/sensitivity and predictive values of urine spot metanephrines-to-creatinine ratios to diagnose canine pheochromocytomas and to determine whether there is a correlation between urine catecholamine levels and tumor volume. In a retrospective study, 32 client-owned dogs with adrenal tumors were identified (13 nonpheochromocytoma and 19 pheochromocytoma). Medical records were evaluated for patients undergoing adrenalectomy between August 2020 and August 2023. Patients were divided into groupings of pheochromocytoma and other adrenal tumor diagnosis on the basis of histopathology. Urine spot normetanephrine concentrations were significantly elevated in dogs with pheochromocytomas compared to dogs with other adrenal tumors. Sensitivity was 78.9%, specificity 76.9%, positive predictive value 83.3%, and negative predictive value 71.4% for discriminating between pheochromocytoma and nonpheochromocytoma. Spot urine metanephrine concentrations were not significantly different between the 2 groups. Only 5 of 19 pheochromocytoma patients had urine normetanephrine concentrations > 4 times the upper reference limit, which is the previously established diagnostic cutoff. Median tumor volume did not correlate with normetanephrine values, nor did those values correlate to patients that experienced intraoperative complications. Twenty-one percent of cases were biochemically silent pheochromocytomas. Urine normetanephrine-to-creatinine levels but not metanephrine-to-creatinine levels can potentially differentiate a pheochromocytoma from a nonpheochromocytoma. Previously published guidelines of 4 times the upper reference limit in spot urine metanephrines testing used to diagnose pheochromocytomas will lead to a significant number of missed diagnoses.

The Discovery and Evolution of a Radio Continuum and Excited-OH Spectral-line Outburst in the Nearby Galaxy NGC 660

Arecibo 305 m Telescope observations between 2008 and 2018 detected a radio continuum and spectral-line outburst in the nearby galaxy, NGC 660. Excited-OH maser emission/absorption lines near 4.7 GHz, and H2CO absorption at 4.83 GHz varied on timescales of months. Simultaneously, a continuum outburst occurred in which a new compact component appeared, with a GHz-peaked spectrum and a 5 GHz flux density that rose to a peak value of about 500 mJy from 2008.0 to 2012.0. Follow-up interferometric continuum images from the Very Large Array at 10 GHz of this new continuum component determined it to be located at the nucleus of NGC 660. Subsequent High Sensitivity Array line and continuum very long baseline interferometry observations of the NGC 660 nucleus revealed a morphology that appears to be consistent with rapidly precessing, mildly relativistic jets from the central black hole. While requiring detailed modeling, this strongly suggests that the outburst is due to nuclear activity. From its timescale, the shape of the continuum light curve, and the milliarcsec radio structure, the most likely cause of the outburst is active galactic nuclei-type activity of accretion of a gas cloud onto the central black hole.

Green synthesis of fluorescent N-doped carbon quantum dots from castor seeds and their applications in cell imaging and pH sensing.

Water-soluble fluorescent N-doped carbon quantum dots (N-CQDs) were hydrothermally prepared through a green synthesis route using castor seeds as a single precursor and a hydrothermal method. Several experimental techniques have been used to characterize synthesized N-CQDs to confirm their structure and to verify their applicability in cell imaging and pH sensing. The synthesized N-CQDs were found to have are characterized by amorphous nature with a spherical shape with an average particle size of 6.57nm as revealed from XRD and TEM measurements. The FTIR results reveal the presence of carboxylic and hydroxyl functional groups on the surface of the CQDs, which was also confirmed by XPS analysis. The fluorescence characterization of the synthesized N-CQDs showed blue emission and excitation dependence with good photostability. It was found that the optimal excitation and emission wavelengths were (λEx = 360) and (λEm = 432) nm, respectively. The fluorescence quantum yield (QY) of about 9.6% at the optimum excitation wavelength 360nm. Moreover, the fluorescence intensity of N-CQDs showed good linear dependence with the pH values in ranges of 3.5 - 7.5 and 8 - 12 as well as high sensitivity for slight changes of pH values. According to these results, two fluorescent pH sensors were created based on acidic and basic media. The obtained N-CQDs have zeta potential of -21.86 mV and thus have excellent stability in water. Moreover, N-CQDs derived from the castor seeds have antimicrobial activity and exhibits low cytotoxicity to WI-13 cells with IC50 = 394.4 ± 13.8µg/mL. The results of this study demonstrated that the synthesized N-CQDs derived from castor seeds can be used as pH sensing and antimicrobial materials. On the other hand, they are also promising in applications in cell imaging, thermo-sensing and optoelectronics.

Inherited Unbalanced Reciprocal Translocation with 18p11.32p11.21 Tetrasomy and 9q34.3 Trisomy in a Fetus Revealed by Cell-Free Fetal DNA (cffDNA) Testing: Cytogenetic and Cytogenomic Characterization in Prenatal Diagnosis

Background/Objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50–80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of gestation, who is a balanced reciprocal translocation 46,XX,t(9;18)(q34;q11.2) carrier, with a high-risk non-invasive prenatal screening test, NIPT, for chromosome 18 aneuploidy. Methods: The highlighted aneuploidy was characterized with cytogenetic, FISH and SNP-array techniques. Results: Cytogenetic analysis, performed on flask-cultured amniocytes, indicated a 48,XX,+2mar karyotype on 50 metaphases. SNP array analysis showed a 15.3 Mb duplication of chromosome 18p (arr[hg19]18p11.32-p11.21(12,842-15,303,932)x4), consistent with a partial tetrasomy 18p, and a 926 kbp duplication of chromosome 9q (arr[GRCh37]9q34.3(140,118,286-141,044,489)x3), consistent with partial trisomy 9q. FISH analysis with a 9q34.3 probe was performed on flask-cultured amniocytes’ metaphases, highlighting the presence of a third signal on one of the two marker chromosomes (18p11.32-p11.21). Conclusions: The evidence of such partial aneuploidies suggests that different mutational events may be possible at meiotic segregation or probably post-meiotic segregation. The results obtained highlight the high sensitivity of the screening test, NIPT, with massive parallel sequencing, and the usefulness of cytogenetics, cytogenomics and molecular biology techniques, in synergy, to characterize and confirm positive NIPT results.

Functional Immunoaffinity 3D Magnetic Core-Shell Nanometallic Structure for High-Efficiency Separation and Label-Free SERS Detection of Exosomes.

Tumor exosomes, known as maternal cell messengers, play an important role in cancer occurrence, proliferation, metastasis, immune escape, drug resistance, and other processes and are an entry point for cancer research. However, there is still a lack of an efficient detection technology for exosomes. In this study, the ultrahigh sensitivity SERS nanoprobe with a three dimensional (3D) magnetic core/Au nanocolumn/Au nanoparticles shell strongly coupling multistage structure (Fe3O4@NR-NPs) was constructed by crystal growth of nanocrystals in the confined space of a central radiating single particle mesoporous molecular sieve channel and strong coupling secondary growth of gold particles. The exosomes were confined onto the "hot spot" of plasmonic nanoparticles and rapidly enriched by CD63 antibody functional-Fe3O4@NR-NPs to achieve high sensitivity detection, with the limit of detection of 1 × 103 particles/mL (S/N = 3). The spectral data set of different exosomes is applied to train for multivariate classification of cell types and to estimate how the normal exosome data resemble cancer cell exosomes by principal component analysis (PCA). Finally, this detection method has also been successfully employed for the detection of exosomes in complex samples; this proves that the proposed SERS-based method is a promising tool for clinical cancer screening.

Tailoring rhodium-based metal-organic layers for parahydrogen-induced polarization: achieving 20% polarization of 1H in liquid phase

Abstract Heterogeneous catalysts for parahydrogen-induced polarization (HET-PHIP) would be useful for producing high sensitivity contrasting agents for magnetic resonance imaging (MRI) in liquid phase, as they can be removed by simple filtration. Although homogeneous hydrogenation catalysts are highly efficient for PHIP, their sensitivity decreases when anchored on porous supports due to slow substrate diffusion to the active sites and rapid depolarization within the channels. To address this challenge, we explored two-dimensional (2D) metal-organic layers (MOLs) as supports for active Rh complexes with diverse phosphine ligands and tunable hydrogenation activities, taking advantage of accessible active sites and chemical adaptability of the MOLs. By adjusting the electronic properties of phosphines, TPP-MOL-Rh-dppb (TPP = tris(4-carboxylphenyl)phosphine), featuring a κ2-connected di(phosphine) ligand, generated hyperpolarized styrene achieving over 2400-fold signal enhancement and polarization level of 20% for 1H in methanol-d4 solution. The TPP-MOL-Rh-dppb effectively inherited the high efficiency and pairwise addition of its homogenous catalyst while maintaining the heterogeneity of MOL. This work demonstrates the potential of 2D phosphine-functionalized MOLs as heterogenous solid support for HET-PHIP.

Abstract A051: Identifying patterns of cell-free DNA associated with elevated risk of diffuse large B-cell lymphoma in adult dogs

Abstract Background: Nonrandom patterns of cell-free DNA (cfDNA) are closely associated with malignancy. We hypothesize that they are also found in the systemic microenvironment that gives rise to cancer, and that such signatures can inform a risk stratification test. To achieve this, we have initiated the Lymphoma Risk Assessment (LyRA) study, using machine learning on a training set of dogs with known health status and a test set of otherwise healthy adult pet dogs to identify cfDNA signatures that are associated with elevated risk of developing diffuse large B- cell lymphoma (DLBCL). We will validate the predictive accuracy of these signatures, including the persistence of the risk environment and the interval between risk detection and development of clinical disease. Since cfDNA is the primary input of the LyRA test, we first performed a pilot study to assess how sample characteristics affect cfDNA quality and subsequent low-pass whole genome sequencing (WGS) data. Methods: Blood samples were collected from pet dogs with the owner’s informed consent. Paired samples were collected into potassium (K3)EDTA tubes and additive-free red top tubes (n = 5 dogs) or K3EDTA tubes and Cell-free DNA BCT® Streck Tubes (n = 6 dogs). Additional serum samples (n=3) were generously provided by the Morris Animal Foundation Golden Retriever Lifetime Study. cfDNA was isolated using the QIAamp® Circulating Nucleic Acid kit. Total cfDNA concentration was measured by PicoGreen™ and fragment distribution by Agilent High Sensitivity D500 ScreenTape® Assay, with comparisons made by starting material (plasma vs. serum) and collection tubes. Results: Serum had both higher total concentrations of cfDNA (PicoGreen™) and calibrated concentrations of long fragment cfDNA (515-658 bp Agilent traces) compared to plasma. In addition, total cfDNA concentrations increased with malignancy, following the pattern: no cancer < cancer < hematological cancer. Median fragment lengths of Agilent peaks also increased with malignancy for short (125-181 bp) and medium (340-425 bp) fragments, in both serum and plasma, but decreased for long fragments. In these pilot data the trends seen were consistent with our hypothesis and with prior studies, although due to sample size, no statistical testing was performed. Conclusions: The pilot study demonstrated that the effects of sample parameters on cfDNA quality are consistent with existing literature, validating our methods and supporting the rationale for the LyRA study. These features may prove valuable when integrated with genomic data to identify high-risk microenvironments. Recent research has shown that a majority of cfDNA in tumor patients originates from non-malignant cells and current methods often overlook potentially important patterns in this so-called 'discard cfDNA.' By focusing on these overlooked patterns, with an emphasis on risk stratification, the LyRA test could shift clinical management to a prevention-focused approach, serving as a model of testing and interception for DLBCL and other cancers in dogs, and potentially in humans. Citation Format: Lauren E Burt, Amy E Treeful, Mitzi Lewellen, Kimberly Demos-Davies, Andrea Chehadeh, Sara Pracht, Ashley J Schulte, Caitlin Feiock, Julia Medland, Davis Seelig, Kelly M Makielski, Ali Khammanivong, Antonella Borgatti, Michael S Henson, Michael Linden, Daniel Vallera, Gary R Cutter, Aaron L Sarver, Jaime F Modiano. Identifying patterns of cell-free DNA associated with elevated risk of diffuse large B-cell lymphoma in adult dogs [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A051.

Design Rules for 3D Printing‐Assisted Pressure Sensor Manufacturing: Achieving Broad Pressure Range Linearity

AbstractRecent advancements in 3D printing technology have expanded its application to manufacturing pressure sensors. By harnessing the cost‐effectiveness, streamlined processes, and design flexibility of 3D printing, sensor fabrication can be customized to meet specific performance needs. Thus far, 3D printing in pressure sensor development has been primarily limited to creating molds for transferring patterns onto flexible substrates, restricting both material selection and sensor performance. To fully unlock the potential of 3D printing in advanced pressure sensor fabrication, it is crucial to establish effective design rules focused on enhancing the figure of merit performance. This study introduces a universal design strategy aimed at maintaining high sensitivity across a wide pressure range—a challenging feat, as sensitivity significantly decreases at higher pressures. Our approach centers on engineering the deformability of 3D‐printed structures, achieving a linear increase in contact area between sensor patterns and electrodes without reaching saturation. Sensors designed with high elongation and low stiffness exhibit consistent sensitivity of 162.5 kPa⁻¹ across a broad pressure range (0.05–300 kPa). Mechanistic investigations through finite element analysis confirm that engineered deformability is key to achieving this enhanced linear response, offering robust sensing capabilities for demanding applications such as deep‐sea and space exploration.

Abstract A053: Liquid biopsy-based detection of triple negative breast cancer using DNA methylation biomarkers

Abstract Triple-negative breast cancer (TNBC) presents significant clinical challenges due to its aggressive phenotype, rapid progression, and limited targeted treatment options. TNBC often mimics benign lesions on ultrasound and metastatic features can be missed in routine mammography screening leading to misdiagnosis and delayed treatment. These limitations led us to investigate whether a blood-based liquid biopsy could provide a non-invasive, sensitive method for early TNBC detection, potentially overcoming the constraints of conventional imaging techniques. To discover biomarkers for TNBC, we performed targeted bisulfite sequencing on a cohort of 46 breast cancer solid tissue biopsy samples, comprising 19 TNBC and 27 non-TNBC cases. We identified 150 differentially methylated regions (mean length 703bp) separating TNBC and non-TNBC samples. Upon linking each region to its nearest gene, we observed several genes previously associated with prognosis and survival (HOXB3, PAX9, SOX9) substantiating the clinical relevance of these biomarkers. Using public TCGA data (369 breast cancer samples), we integrated expression and methylation data and observed directionally consistent changes. For example, HOXB3 showed increased methylation at its associated differential regions and decreased expression in TNBC cases. To ascertain whether these biomarkers could be useful in a liquid biopsy approach, we performed targeted bisulfite- sequencing on cell-free DNA samples derived from prospectively collected patients with breast cancer. All samples had independent tissue-based assessment of ER, PR and HER2 using immunohistochemistry or in situ hybridization. We then built a feed-forward neural network classifier with classes TNBC and non-TNBC that used transfer-learning and the identified biomarkers to learn methylation signatures in the biopsy samples and map them to cell-free DNA. To emulate clinical workflow, where subtyping follows cancer diagnosis and tissue of origin identification, we evaluated cfDNA samples correctly identified as breast cancer using two independent machine learning models trained using 2,393 prospectively collected multi- indication cancer and non-cancer samples (NCT05435066). Subsequent TNBC subtyping of breast cancer-positive cases (N=56) accurately identified 77% (10/13) of TNBC samples and 91% (39/43) of non-TNBC cases, with overall accuracy of 84%. The estimated tumor content range for correctly predicted TNBC samples was 0.5-33% with the three mis-classified samples all showing very low tumor content (0.22%, 0.28%, 0.59%). Non-TNBC cases showed a tumor content range of 0.07-36% for correct and 2.3-14% for misclassified samples. In conclusion, we identified novel methylation biomarkers that distinguish TNBC in the cell-free DNA of patients without needing invasive tissue biopsies. The high sensitivity of our assay at low tumor fractions has the potential to improve outcomes through earlier intervention and may enable earlier screening in high-risk groups, monitoring of minimal residual disease and longitudinal monitoring during treatment. Citation Format: Jocelyn Charlton, Shiva Farashahi, Kade Pettie, Elie Massaad, Josh Hubbell, Feras Hantash, Kieran I Chacko. Liquid biopsy-based detection of triple negative breast cancer using DNA methylation biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A053.

Abstract A020: Enhanced cell-free RNA (cfRNA) recovery for liquid biopsy applications: Comparative analysis using controlled RNA samples for early and advanced cancer detection

Abstract Introduction: Extracting cfRNA from biological samples is crucial in liquid biopsy applications, particularly for detecting low-frequency mutations like KRAS G12V, essential for early cancer diagnosis and minimal residual disease (MRD) monitoring. Traditional cfRNA extraction methods involve multiple transfer steps, aliquoting, and pooling, leading to cfRNA loss and affecting mutation detection sensitivity and accuracy. The nRichDX Revolution cfTNA Max 20 kit, with its innovative nRicher cartridge, simplifies the extraction process by eliminating these extra steps, potentially enhancing yield and efficiency. This study evaluates the cfRNA recovery efficiency of the nRichDX kit compared to the Qiagen Circulating Total Nucleic Acid kit. Methods: Plasma samples (5 mL each) were spiked with RNA containing KRAS G12V mutation at concentrations ranging from 100 to 2 million copies, mimicking early-stage cancer detection and MRD monitoring, where low copy numbers represent early disease and high copy numbers reflect advanced cancer stages. cfRNA was extracted using the nRichDX and Qiagen kits, with each condition tested in triplicate. cfRNA recovery efficiency was assessed using quantitative reverse transcription PCR (qRT-PCR) to quantify KRAS G12V RNA copies recovered. High-sensitivity RNA ScreenTape Analysis was also used to evaluate cfRNA profile quality. Results: The nRichDX kit recovered significantly higher cfRNA yields than Qiagen across all concentrations. Recovery rates were consistent and reproducible, with over 70% of input RNA recovered, even at lower inputs (100 to 100,000 copies), where recovery rates were approximately 70-85%. High Sensitivity RNA ScreenTape Analysis showed a linear increase in 18S and 28S ribosomal peaks and high RNA Integrity Number (RIN) scores in nRichDX profiles. The ability to robustly recover low copy numbers is significant for early cancer detection and MRD monitoring. In contrast, the kit’s effectiveness in high copy number samples reflects its ability to monitor advanced cancer stages accurately. Conclusion: The nRichDX cfTNA kit demonstrates exceptional efficiency in cfRNA extraction from plasma samples across a broad dynamic range, from as few as 100 copies to as many as 2 million copies of the KRAS G12V mutation. Its versatility makes it suitable for various cancer detection and monitoring applications. The streamlined process offered by the nRicher cartridge minimizes sample handling and reduces cfRNA loss, enhancing performance. This translates to more accurate and sensitive detection of early-stage and high-burden mutations associated with advanced cancer. The high-quality profiles indicated by RNA ScreenTape Analysis further validate the reliability of the nRichDX kit, making it a valuable tool for liquid biopsy applications, with significant advantages in early cancer detection and monitoring disease progression. Citation Format: Nafiseh Jafari, Mayer Saidian, Jason Saenz, Andrew Dunnigan, Carlos Hernandez, Leila Aghili. Enhanced cell-free RNA (cfRNA) recovery for liquid biopsy applications: Comparative analysis using controlled RNA samples for early and advanced cancer detection [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A020.

Enhanced long-lasting luminescence nanorods for ultrasensitive detection of SARS-CoV-2 N protein

AbstractPersistent luminescence nanomaterials can remain luminescence when the light source is turned off, which exhibits promise in biosensor and bioimaging fields since they have the ability to completely eradicate tissue autofluorescence. Although significant progress has been made in the persistent luminescence biosensing, there is still a dearth of long-afterglow detection platform with low limit of detection (LOD) and high sensitivity. Herein, Zn2GeO4:Mn, Cr persistently luminescent nanorods (PLNRs) with superior persistent luminescence and long afterglow time were developed. The addition of Cr3+ manifestly improves persistent luminescence intensity and afterglow duration through creating a deep defect trap. Then the biosensors were constructed by combining the Zn2GeO4:Mn,Cr PLNRs-antibody and Fe3O4 magnetic nanoparticles (MNPs)-antibody for nucleocapsid protein detection based on electrostatic attraction. The LOD value for nucleocapsid protein realizes as low as 39.82 ag/mL, which is much lower than the previously reported persistent luminescent-based biosensors. Accordingly, the low detection sensitivity is attributed to fluorescence resonance energy transfer. In addition, high specificity is also achieved. Therefore, the as-prepared Zn2GeO4:Mn,Cr persistently luminescent materials can act as the promising candidate in biosensors applications. This strategy provides effective guidance for the development of biosensing platforms with high sensitivity and specificity.

Tetraphenylethene-Based Covalent Organic Polymers with Aggregation-Induced Electrochemiluminescence for Highly Sensitive Bacterial Biosensors.

Tetraphenylethene (TPE), which usually serves as aggregation-induced emission and aggregation-induced electrochemiluminescence fluorophores, has been widely applied in fabricating fluorescent nanomaterials and biosensors. However, it is still a tremendous challenge to prepare well-controlled TPE aggregates with strong fluorescence (FL) and electrochemiluminescence (ECL). In this study, we constructed a bacterial ECL biosensing platform with high sensitivity based on TPE-based covalent organic polymer (COP) nanoparticles synthesized by a simple Menschutkin reaction strategy to employ bromide group-carrying molecules and 1,1,2,2-tetrakis(4-(pyridine-4-yl)phenyl)ethene as the cross-linking agent and the emissive moiety, respectively. The ECL Escherichia coli biosensor had high sensitivity, a low limit of detection (0.19 CFU mL-1), a wide linear range (1 × 102-5 × 106 CFU mL-1), and good selectivity. The excellent properties of the bacterial biosensor could be attributed to the uniform spherical COP nanoparticles with enhanced FL and ECL signals, the maximal ECL efficiency of which was 8.4-fold higher than that of the typical tris(bipyridine) ruthenium(II) emitter. The FL and ECL intensities of the TPE-based COP nanoparticles could be adjusted by varying bromide group-carrying molecules and thus regulating their energy gap between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals. The TPE-based COP nanoparticles with strong FL and ECL intensities pave a promising avenue to construct highly sensitive bacterial ECL biosensors for the large-scale screening of disease-causing bacteria.

Steady-State Inverse-Temperature Crystallization Enabling Low Defect Perovskite Single Crystal and Efficient X-Ray Detectors.

Organic-inorganic halide perovskite single crystals (SCs) have shown great potential in radiation detection applications due to their large radiation stopping power and excellent carrier transport properties. The spatial-confined inverse-temperature crystallization (ITC) method has been widely adopted to obtain large-sized SCs. However, they usually face the problems of uneven stress distribution and high defect density due to the limited crystal growth space and varied growth rate with the increase in temperature, making it difficult to fabricate highly sensitive and stable radiation detectors. In this study, the steady-state inverse-temperature crystallization method (SS-ITC) is developed to regulate the growth process of SCs by controlling the growth speed precisely to achieve a constant rate of growth as the temperature increases. Compared with the conventional ITC-grown samples, the lattice spacing of SCs prepared by the SS-ITC method is reduced by 1.2% due to tensile stress relaxation, resulting in a lower defect density of 7.93×109cm-3 and a remarkable uniformity over a large area. As a result, the co-planar X-ray detectors based on these high-quality SCs exhibit a high sensitivity of 1.67×105 µC Gyair -1cm-2, representing the best performing MAPbBr3-based X-ray detectors reported to date.

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in 26 BBS genes. It affects multiple organs, including the kidney and liver, with varying degrees regarding extent and time of first manifestation. Structural renal anomalies are an early feature and end-stage kidney disease (ESKD) cumulates to 25% in adulthood. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Patients with genetically proven BBS were recruited from the University Children's Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients' digital records or medical letters. High-resolution ultrasound (US) imaging was utilized, including attenuation imaging (ATI), shear wave elastography (SWE) and dispersion (SWD) of liver tissue. 49 BBS patients (24/49 male; 1.1-51.0years, mean 17.8years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48), and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) of whom 3 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49), suggesting hepatic fibrosis, and it correlated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI, reduced GFR, and higher BMI SDS. We detected kidney and liver abnormalities in a higher percentage of BBS patients than previously reported, indicating a high sensitivity and diagnostic yield of the evaluated high-end US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.

Highly sensitive liquid refractive index sensor based on a polymer two-mode ridge waveguide interferometer

In this paper, we propose and experimentally demonstrate a highly sensitive liquid refractive index (RI) sensor based on a two-mode interferometer (TMI) formed with a polymer ridge waveguide. Compared with the rectangular waveguide TMI sensor, our proposed ridge waveguide TMI sensor enables a higher waveguide sensitivity and hence device sensitivity. Our experimental results show that the fabricated ridge waveguide TMI sensor achieves a sensitivity of 6980.62 nm/RIU, indicating a significant improvement over the fabricated rectangular waveguide TMI sensor with almost identical dimensions; the latter exhibits a sensitivity of 3753.81 nm/RIU. Our proposed sensor is simple in structure but has high sensitivity and low cost.

Development of a simple, low-cost, blue light-emitting diode illuminator for hands-on training of DNA detection experiments using agarose gel electrophoresis.

DNA detection by agarose gel electrophoresis (AGE) is commonly used in molecular biology. AGE is a separation method that provides opportunities for students to learn about the topology and size of DNA molecules. Recently, several fluorescent dyes have been used for DNA staining owing to their convenience, safety, reduced toxicity, and high sensitivity. A blue light-emitting diode (LED) transilluminator is required to detect DNA using fluorescent dyes; however, the associated high cost may limit its availability in classrooms or small laboratories. Therefore, we have designed a simple, low-cost blue LED illuminator to enable easy assembly for instructors and students. We evaluated the performance of the proposed illuminator by observing fluorescent dye-stained DNA markers using AGE, revealing clear DNA marker bands. Despite its limited functionality, the ease of construction and affordability of the proposed illuminator make it sufficient for hands-on molecular biology training in classrooms, thereby enhancing the learning environment and educational efficiency.

Spatial heterogeneity response of soil salinization inversion cotton field expansion based on deep learning

Soil salinization represents a significant challenge to the ecological environment in arid areas, and digital mapping of soil salinization as well as exploration of its spatial heterogeneity with crop growth have important implications for national food security and salinization management. However, the machine learning models currently used are deficient in mining local information on salinity and do not explore the spatial heterogeneity of salinity impacts on crops. This study developed soil salinization inversion models using CNN (Convolutional Neural Network), LSTM (Long Short-Term Memory Network), and RF (Random Forest) models based on 97 field samples and feature variables extracted from Landsat-8 imagery. By evaluating the accuracy, the best-performing model was selected to map soil salinity at a 30m resolution for the years 2013 and 2022, and to explore the relationship between soil electrical conductivity (EC) values and the expansion of cotton fields as well as their spatial correlation. The results indicate that:(1) The CNN performs best in prediction, with an R2 of 0.84 for the training set and 0.73 for the test set, capable of capturing more local salinity information. (2) The expansion of cotton fields has reduced the level of soil salinization, with the area of severely salinized and saline soils in newly added cotton fields decreasing from 177.91 km2 and 381.46 km2 to 19.49 km2 and 1.12 km2, respectively. (3) Regions with long-term cotton cultivation and newly reclaimed cotton fields exhibit high sensitivity and vulnerability to soil salinity. This study explores the excellent performance of deep learning in salinity mapping and visualizes the spatial distribution of cotton fields that are highly sensitive to soil salinity, providing a scientific theoretical basis for accurate salinity management.

Polypyrrole-bismuth tungstate/polypyrrole core-shell for optoelectronic devices exhibiting Schottky photodiode behavior.

A polypyrrole-bismuth tungstate (Ppy-Bi2WO6) core-shell nanocomposite (n-type material) has been developed on a layered Ppy (p-type) base as an efficient light-capturing material exhibiting photodiode behavior. This device demonstrates promising sensitivity for light sensing and captures across a broad spectral range, from near IR to UV. The Bi2WO6/Ppy nanocomposite boasts an optimal bandgap of 2.0eV, compared to 3.4eV for Ppy and 2.5eV for Bi2WO6. The crystalline size of the core-shell composite is approximately 21nm, emphasizing its photon absorption capabilities. The composite particles, around 100nm in length, feature a highly porous morphology that effectively traps incident photons. The performance of this optoelectronic device is evaluated using current density (J) measurements under light (Jph) and dark (Jo) conditions. In darkness, the n-p type semiconductor exhibits limited current with a Jo of -0.22mA cm-2 at 2.0V. When exposed to white light, the Ppy- Bi2WO6/Ppy device generates hot electrons, achieving a Jph value of 1.1mA/cm-2 at 2.0V. It shows a superior responsivity (R) of 6.6mA/W at 340nm, gradually decreasing to 6.3mA/W at 440nm and 4.2mA/W at 540nm, indicating high sensitivity across the UV-Vis spectrum. At 730nm, the R-value is 2.6mA/W, highlighting its sensitivity in the near IR region. Additionally, at 340nm, the device achieves a detectivity (D) value of 0.15 × 10¹⁰ Jones, which decreases with longer wavelengths to 0.14 × 10¹⁰ Jones at 440nm, 0.9 × 10⁹ Jones at 540nm, and 0.63 × 10⁹ Jones at 730nm. With its great stability, low cost, easy fabrication, and potential for mass production, this optoelectronic light sensor and photodiode device holds significant promise for industrial applications as a highly effective optoelectronic device.

Wearable System Integrating Dual Piezoresistive and Photoplethysmography Sensors for Simultaneous Pulse Wave Monitoring.

Wearable, flexible piezoresistive pressure sensors have garnered substantial interest due to their diverse applications in fields such as electronic skin, robotic limbs, and cardiovascular monitoring. Among these applications, arterial full pulse waveform monitoring stands out as a critical area of research. The emergence of piezoresistive pressure sensors as a prominent tool for capturing pulse waveforms has led to extensive investigations. However, the lack of a linear response while achieving high sensitivity, limited compactness of signal collection systems, and scaling issues are a few potential causes of the gap between research advances and technology market readiness. Here, we present a scalable dual piezoresistive sensor that uses two complementary resistance-changing mechanisms to balance the trade-off between linear response and high sensitivity. This synergic design enables excellent sensitivity of 8.4 kPa-1 and near linear pressure response. It boasts a fast response time of 95/145 ms for loading and unloading at a pressure of 10.1 kPa. The durability tests, encompassing nearly 5000 two-stage compression cycles, validate the reliable performance of the sensor, even after prolonged use. Leveraging these performance metrics, we developed a high-resolution and compact signal collection device capable of accurately detecting the three distinct peaks associated with the full pulse waveform, including the systolic and reflected diastolic peaks. Moreover, the signal acquisition system incorporates a photoplethysmography sensor, which, when paired with the dual piezoresistive sensor, offers new insights into localized vascular health monitoring. The unique feature of our approach is its ability to perform localized vascular monitoring using multiple sensors placed on different veins. The simultaneous detection of forward- and backward-going pulse waves at the body extremities allows for a comprehensive evaluation of localized vascular health, which is not achievable with a single sensor. Finally, the comparison of wrist pulse waveforms between the compact signal collection device and a standard sourcemeter (such as the Keithley 2460) confirmed that the wearable sensing system is on par with conventional sourcemeters in terms of capturing the typical details of the full pulse waveform (i.e., systolic peak, dicrotic notch, and diastolic peak). This validation underscores the reliability and effectiveness of the developed wearable sensing system for practical and continuous pulse waveform monitoring.