Aptamer-based carbohydrate antigen 125 sensor with molybdenum disulfide functional hybrid materials.

Epithelial ovarian cancer is a malignant tumor of the female reproductive system with insidious symptoms, aggressiveness, risk of metastasis, and high mortality. Carbohydrate antigen 125 (CA125), a standard biomarker for screening epithelial ovarian cancer, can be applied to track cancer progression and treatment response. Here, we constructed an aptamer-based electrochemical biosensor to achieve sensitive detection of CA125. Molybdenum disulfide (MoS2) was used as the stable layered substrate, combined with the irregular branched structure of gold nanoflowers (AuNFs) to provide the sensing interface with a large specific surface area by one-step electrodeposition AuNFs@MoS2. The simplified electrode modification step increased the stability of the electrode while ensuring excellent electrochemical performance and providing many sulfhydryl binding sites. Then, AuNFs@MoS2/CA125 aptamer/MCH sensor was designed for CA125 detection. Based on AuNFs@MoS2 electrode, CA125 aptamer with sulfhydryl as the sensitive layer was fixed on the electrode by gold sulfur bonds. 6-Mercapto-1-hexanol (MCH) was used to block the electrode and reduce the non-specific adsorption. Finally, DPV analysis was applied for CA125 detection with the range of 0.0001 U/mL to 500 U/mL. Our designed aptamer sensor showed reasonable specificity, reproducibility, and stability. Clinical sample testing also proved the consistency of our sensor with the gold standard in negative/positive judgment. This work demonstrated a novel strategy for integrating nanostructures and biocompatibility to build advanced cancer biomarker sensors with promising applications.

γ-Hemolysin Nanopore Is Sensitive to Guanine-to-Inosine Substitutions in Double-Stranded DNA at the Single-Molecule Level.

Biological nanopores provide a unique single-molecule sensing platform to detect target molecules based on their specific electrical signatures. The γ-hemolysin (γ-HL) protein produced by Staphylococcus aureus is able to assemble into an octamer nanopore with a ∼2.3 nm diameter ß-barrel. Herein, we demonstrate the first application of γ-HL nanopore for DNA structural analysis. To optimize conditions for ion-channel recording, the properties of the γ-HL pore (e.g., conductance, voltage-dependent gating, and ion-selectivity) were characterized at different pH, temperature, and electrolyte concentrations. The optimal condition for DNA analysis using γ-HL corresponds to 3 M KCl, pH 5, and T = 20 °C. The γ-HL protein nanopore is able to translocate dsDNA at about ∼20 bp/ms, and the unique current-signature of captured dsDNA can directly distinguish guanine-to-inosine substitutions at the single-molecule level with ∼99% accuracy. The slow dsDNA threading and translocation processes indicate this wild-type γ-HL channel has potential to detect other base modifications in dsDNA.

A dual-targeted electrochemical aptasensor for neuroblastoma-related microRNAs detection.

Neuroblastoma (NB) is a significant pediatric cancer associated with high mortality rates, demanding innovative and appropriate approaches for its accurate detection. This paper described the design of a dual-target electrochemical aptasensor capable of simultaneously detecting neuroblastoma-associated microRNAs (miRNA-181 and miRNA-184) with exceptional sensitivity. Screen-printed carbon electrodes (SPCEs) were utilized with gold nanorods (AuNRs), and aptamers functionalized gold nanoparticles (AuNPs) to improve sensitivity, specificity, and portable detection ability. The detection method employed in this study includes differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Our aptasensor exhibited remarkable limits of detections (LODs) of 5.10 aM for miRNA-181 and 9.39 aM for miRNA-184, respectively, along with a broad linear range spanning from 0.1 fM to 100 pM for both miRNAs. The practical significance of neuroblastoma diagnosis was shown through the validation of serum samples and comparison with quantitative polymerase chain reaction (qPCR). Our electrochemical aptasensor is user-friendly, easy to engineer, and offers a promising approach for accurately and selectively detecting important miRNA biomarkers in cancer screening and diagnosis, showing potential application in various clinical scenarios.

Experiences of Health-Care Professionals Who Served the Migrant Workers During the COVID-19 Pandemic in Singapore and Its Impact on Morale: A Brief Report.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused psychological distress among health-care professionals (HCP) worldwide, suggesting that morale could also be affected. This warrants further investigation as HCPs' morale directly impacts delivery of quality care and work productivity. This study aims to explore the experiences of HCPs who served migrant workers in a local COVID-19 hotspot in Singapore and the impact on their morale. METHODS: Eleven volunteer HCPs from a regional hospital in Singapore who served migrant workers in a local COVID-19 hotspot were recruited. Semi-structured face-to-face interviews were conducted, and recordings were transcribed verbatim. Transcripts were analyzed using thematic analysis. Morale of HCPs was evaluated based on responses. RESULTS: Four main themes emerged: motivators, challenges, support, and leadership. Motivators or factors that drove HCPs to serve include varying personal reasons and a sense of duty to do good. Challenges faced by HCPs include a language barrier, keeping up with rapidly changing workflows, fear of contagion, and coping with emotions. Support and leadership were revealed to have boosted HCPs' morale. CONCLUSIONS: Peer and social support and effective leadership have potential protective effects on HCPs' morale against negative experiences faced during the COVID-19 pandemic.

AB077. An evaluation of prognostic scoring systems for survival in a surgically treated cohort of 318 metastatic spine tumour surgery patients.

BACKGROUND: Survival prognostication plays a key role in the decision-making process for the surgical treatment of patients with spinal metastases. In the past traditional scoring systems such as the modified Tokuhashi and Tomita scoring systems have been used extensively, however in recent years their accuracy has been called into question. This has led to the development of machine learning algorithms to predict survival. In this study, we aim to compare the accuracy of prognostic scoring systems in a surgically treated cohort of patients. METHODS: This is a retrospective review of 318 surgically treated spinal metastases patients between 2009 and 2021. The primary outcome measured was survival from the time of diagnosis. Predicted survival at 3 months, 6 months and 1 year based on the prognostic scoring system was compared to actual survival. Predictive values of each scoring system were measured via area under receiver operating characteristic curves (AUROC). The following scoring systems were compared, Modified Tokuhashi (MT), Tomita (T), Modified Bauer (MB), Van Den Linden (VDL), Oswestry (O), New England Spinal Metastases score (NESMS), Global Spine Study Tumor Group (GSTSG) and Skeletal Oncology Research Group (SORG) scoring systems. RESULTS: For predicting 3 months survival, the GSTSG 0.980 (0.949-1.0) and NESM 0.980 (0.949-1.0) had outstanding predictive value, while the SORG 0.837 (0.751-0.923) and O 0.837 (0.775-0.900) had excellent predictive value. While for 6 months survival, only the O 0.819 (0.758-0.880) had excellent predictive value and the GSTSG 0.791(0.725-0.857) had acceptable predictive value. For 1 year survival, the NESM 0.871 (0.822-0.919) had excellent predictive value and the O 0.722 (0.657-0.786) had acceptable predictive value. The MT, T and MB scores had an area under the curve (AUC) of <0.5 for 3-month, 6-month and 1-year survival. CONCLUSIONS: Increasingly, traditional scoring systems such as the MT, T and MB scoring systems have become less predictive. While newer scoring systems such as the GSTSG, NESM and SORG have outstanding to excellent predictive value, there is no one survival scoring system that is able to accurately prognosticate survival at all 3 time points. A multidisciplinary, personalised approach to survival prognostication is needed.

AB078. Patterns of treatment delay in patients with symptomatic metastatic epidural spinal cord compression.

BACKGROUND: Delayed treatment in symptomatic metastatic epidural spinal cord compression (MESCC) is significantly associated with poorer functional outcomes. In this study, we aim to identify the patterns of treatment delay in patients and factors predictive of postoperative ambulatory function. METHODS: Retrospective review of patients with symptomatic MESCC treated surgically between January 2015 and January 2022. MESCC symptoms were categorized into symptoms suggesting cord compression requiring immediate referral and symptoms suggestive of spinal metastases. Multivariate analysis was performed to identify factors predictive of postoperative ambulatory function. Delays in treatment were identified and categorized into patient delay (onset of symptoms till initial medical consultation), diagnostic delay (medical consultation till radiological diagnosis of MESCC), referral delay (from diagnosis till spine surgeon review) and surgical delay (from spine surgeon review till surgery) and compared between patients. RESULTS: One hundred and seventy-eight patients were identified. In this cohort 92 (52.0%) patients were able to ambulate independently, and 86 (48.3%) patients were non independent. One hundred and thirty-nine (78.1%) of patients had symptoms of cord compression and 93 (52.3%) had neurological deficits on presentation. On multivariate analysis, pre-operative neurological deficits (P=0.01) and symptoms of cord compression (P=0.01) were significantly associated with post-operative ambulatory function. Mean total delay was 66 days, patient delay was 41 days, diagnostic delay was 16 days, referral delay was 3 days and surgical delay was 6 days. In patients with neurological deficits, there was a significant decrease in all forms of treatment delay (P<0.05). There was no significant decrease in patient delay, diagnostic delay and referral delay in patients with symptoms of cord compression. CONCLUSIONS: Both patients and physicians understand the need for urgent surgical treatment of MESCC with neurological deficits, however there is still a need for increased education and recognition of the symptoms of MESCC.

Microfluidic Liver-on-a-Chip for Preclinical Drug Discovery.

Drug discovery is an expensive, long, and complex process, usually with a high degree of uncertainty. In order to improve the efficiency of drug development, effective methods are demanded to screen lead molecules and eliminate toxic compounds in the preclinical pipeline. Drug metabolism is crucial in determining the efficacy and potential side effects, mainly in the liver. Recently, the liver-on-a-chip (LoC) platform based on microfluidic technology has attracted widespread attention. LoC systems can be applied to predict drug metabolism and hepatotoxicity or to investigate PK/PD (pharmacokinetics/pharmacodynamics) performance when combined with other artificial organ-on-chips. This review discusses the liver physiological microenvironment simulated by LoC, especially the cell compositions and roles. We summarize the current methods of constructing LoC and the pharmacological and toxicological application of LoC in preclinical research. In conclusion, we also discussed the limitations of LoC in drug discovery and proposed a direction for improvement, which may provide an agenda for further research.

Unlocking the Power of Nanopores: Recent Advances in Biosensing Applications and Analog Front-End.

The biomedical field has always fostered innovation and the development of various new technologies. Beginning in the last century, demand for picoampere-level current detection in biomedicine has increased, leading to continuous breakthroughs in biosensor technology. Among emerging biomedical sensing technologies, nanopore sensing has shown great potential. This paper reviews nanopore sensing applications, such as chiral molecules, DNA sequencing, and protein sequencing. However, the ionic current for different molecules differs significantly, and the detection bandwidths vary as well. Therefore, this article focuses on current sensing circuits, and introduces the latest design schemes and circuit structures of different feedback components of transimpedance amplifiers mainly used in nanopore DNA sequencing.

Functionalized GD2 Electrochemical Immunosensor to Diagnose Minimum Residual Disease of Bone Marrow in Neuroblastoma Effectively.

Neuroblastoma (NB) is known as the "king of childhood tumors" due to its highly metastatic, recurrence-prone, and difficult-to-treat characteristics. International Neuroblastoma Risk Grading Group (INRG) has recommended GD2, a disialoganglioside expressed on neuroectodermal tumor cells, as the target for detecting minimal residual disease in bone marrow metastases of high-risk neuroblastoma in children. Therefore, accurately identifying GD2-positive cells is crucial for diagnosing children with high-risk NB. Here, we designed a graphene/AuNP/GD2 Ab-functionalized electrochemical biosensor for GD2 detection. A three-electrode system was processed using a screen-printed technique with a working electrode of indium tin oxide, a counter electrode of carbon, and a reference electrode of silver/silver chloride. Graphene/AuNPs were modified on the indium tin oxide electrode using chronoamperometric scans, and then, the GD2 antibody was modified on the biosensor by electrostatic adsorption to achieve sensitive and specific detection of GD2-positive cells in bone marrow fluid. The results showed that a graphene/AuNP/GD2 Ab-functionalized electrochemical biosensor achieved GD2-positive cell detection in the range of 102 cells/mL~105 cells/mL by differential pulse voltammetry. Bone marrow fluid samples from 12 children with high-risk NB were retained for testing on our biosensor and showed 100% compliance with the clinical application of the gold-standard immunocytochemical staining technique for detecting GD2-positive cells qualitatively. The GD2-based electrochemical assay can accurately detect children with high-risk NB, providing a rapidly quantitative basis for clinical diagnosis and treatment.

Applications of Smartphone-Based Aptasensor for Diverse Targets Detection.

Aptamers are a particular class of functional recognition ligands with high specificity and affinity to their targets. As the candidate recognition layer of biosensors, aptamers can be used to sense biomolecules. Aptasensors, aptamer-based biosensors, have been demonstrated to be specific, sensitive, and cost-effective. Furthermore, smartphone-based devices have shown their advantages in binding to aptasensors for point-of-care testing (POCT), which offers an immediate or spontaneous responding time for biological testing. This review describes smartphone-based aptasensors to detect various targets such as metal ions, nucleic acids, proteins, and cells. Additionally, the focus is also on aptasensors-related technologies and configurations.