{"title":"Trimethylamine N-oxide detection for early prediction of renal function utilizing a three-dimensional localized electronic structure (3DLES) biosensor","authors":"Wei-Cheng Lin, Wei-Lun Yen, Yun-Yu Hsieh, Bing-Hong Chen, Yi-Huan Chang, Tzu-Wei Chung","doi":"10.1007/s00604-025-07556-5","DOIUrl":null,"url":null,"abstract":"<div><p> A novel Micro-Electro-Mechanical Systems (MEMS) is introduced based biosensor architecture employing a three-dimensional localized electronic structure (3DLES) array capable of detecting trimethylamine N-oxide, (TMAO, (CH₃)₃NO), concentrations as low as 0.2 μM in biological fluids such as urine or serum. The design incorporates a modified Cole–Cole model, wherein newly introduced parameters for the proposed 3DLES array biosensor are able to quantify enzymatic impedance effects. These variables offer insight into redox behavior and the fine-scale electrical currents generated by catalytic activity. On-chip signal processing is incorporated into the system, enabling fast detection within 1 s and Yielding a high sensitivity of 320 ADC units per micromolar (equivalent to 5.5 mV/μM). Very high repetition (98.1%) and low signal drift (0.4 mV over time) further demonstrate the system’s reliability. TMAO detection is facilitated through minute variations in capacitive properties induced by the TorA enzyme, Yielding a detectable differential response of 10.6%. Comparison with traditional cyclic voltammetry (CV) shows excellent agreement, with only 0.024% deviation between methodologies. The 3DLES biosensor also exhibits a high TMAO-to-TMA conversion efficiency (88%) and impressive selectivity (97%) for the target analyte, making it a viable candidate for early-stage renal function assessment in non-clinical settings. The strong correlation between the proposed biosensor and mass spectrometry results across 100 urine samples (<i>R</i><sup>2</sup> = 0.954), along with the extracted linear equation <i>Y</i> = 120.9 − 39.2 × <i>X</i> (where <i>Y</i> is the ADC count of TMAO and <i>X</i> is the UACR), highlights the biosensor’s reliability and effectiveness in quantifying renal function biomarkers. This compact and cost-effective device offers a promising pathway toward at-home renal function pre-screening through metabolic profiling.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":705,"journal":{"name":"Microchimica Acta","volume":"192 11","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microchimica Acta","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s00604-025-07556-5","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
A novel Micro-Electro-Mechanical Systems (MEMS) is introduced based biosensor architecture employing a three-dimensional localized electronic structure (3DLES) array capable of detecting trimethylamine N-oxide, (TMAO, (CH₃)₃NO), concentrations as low as 0.2 μM in biological fluids such as urine or serum. The design incorporates a modified Cole–Cole model, wherein newly introduced parameters for the proposed 3DLES array biosensor are able to quantify enzymatic impedance effects. These variables offer insight into redox behavior and the fine-scale electrical currents generated by catalytic activity. On-chip signal processing is incorporated into the system, enabling fast detection within 1 s and Yielding a high sensitivity of 320 ADC units per micromolar (equivalent to 5.5 mV/μM). Very high repetition (98.1%) and low signal drift (0.4 mV over time) further demonstrate the system’s reliability. TMAO detection is facilitated through minute variations in capacitive properties induced by the TorA enzyme, Yielding a detectable differential response of 10.6%. Comparison with traditional cyclic voltammetry (CV) shows excellent agreement, with only 0.024% deviation between methodologies. The 3DLES biosensor also exhibits a high TMAO-to-TMA conversion efficiency (88%) and impressive selectivity (97%) for the target analyte, making it a viable candidate for early-stage renal function assessment in non-clinical settings. The strong correlation between the proposed biosensor and mass spectrometry results across 100 urine samples (R2 = 0.954), along with the extracted linear equation Y = 120.9 − 39.2 × X (where Y is the ADC count of TMAO and X is the UACR), highlights the biosensor’s reliability and effectiveness in quantifying renal function biomarkers. This compact and cost-effective device offers a promising pathway toward at-home renal function pre-screening through metabolic profiling.
期刊介绍:
As a peer-reviewed journal for analytical sciences and technologies on the micro- and nanoscale, Microchimica Acta has established itself as a premier forum for truly novel approaches in chemical and biochemical analysis. Coverage includes methods and devices that provide expedient solutions to the most contemporary demands in this area. Examples are point-of-care technologies, wearable (bio)sensors, in-vivo-monitoring, micro/nanomotors and materials based on synthetic biology as well as biomedical imaging and targeting.