Dual-Aptamer Drift Canceling Techniques to Improve Long-Term Stability of Real-Time Structure-Switching Aptasensors.

This paper presents a dual-aptamer scheme to mitigate signal drifts caused by structure-switching aptamers during long-term monitoring. Electrochemical aptamer-based (E-AB) biosensors have recently shown great potential for continuous in vivo monitoring. However, the accuracy of detection is often limited by signaling drifts. Traditional approaches rely on kinetic differential measurements (KDM) coupled with square-wave voltammetry to eliminate these drifts. Yet, we have discovered that KDM does not apply universally to all aptamers, as their responses at different SWV frequencies heavily rely on their structure-switching characteristics and the electron transfer (ET) kinetics of the redox reporters. In light of this, we propose a "dual-aptamer" scheme that utilizes two aptamers, each responding differently to the same target molecule to cancel out drift. These paired aptamers are identified through (1) screening from an existing pool of aptamers and (2) engineering the signaling behavior of the redox reporters. We demonstrate the differential signaling of the aptamer pair in the presence of ampicillin and ATP molecules and show that the pair exhibits similar drifts in undiluted goat serum. By implementing drift cancelation, sensor drift is reduced by a factor of 370. Additionally, the differential signaling enables an increased recording throughput by leveraging differential readout electronics. The authors believe that the proposed technique holds significant benefits for long-term in vivo monitoring.

Complete genomic profiles of 1496 Taiwanese reveal curated medical insights.

INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.