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11 pages, 7658 KiB

Open AccessArticle

Colorimetric Detection of microRNA-378 Based on Y-Shaped Structure Formed by Gold Nanoparticles and Catalytic Hairpin Self-Assembly

by Yahui Gao, Jinru Pan, Bingyuan Fan, Shan Wang, Qian Wang, Wanru Liu, Fang Hu and Wei Meng

Biosensors 2025, 15(5), 319; https://doi.org/10.3390/bios15050319 - 15 May 2025

Viewed by 195

Abstract

The timely and accurate detection of cancer is crucial for preventing disease progression and for the early treatment of confirmed cases. MiRNAs are cancer markers. In this study, a simple miRNA detection method is proposed. Three hairpins were designed based on gold nanoparticles [...] Read more.

The timely and accurate detection of cancer is crucial for preventing disease progression and for the early treatment of confirmed cases. MiRNAs are cancer markers. In this study, a simple miRNA detection method is proposed. Three hairpins were designed based on gold nanoparticles combined with catalytic hairpin assembly nucleic acid amplification technology. The low-pH method was used for rapid coupling, and hairpin H1 was opened by miR-378, triggering the cycle reaction and signal amplification and finally forming a Y-shaped structure, thereby narrowing the distance between gold nanoparticles and achieving colorimetric detection. The absorbance change (A₆₂₀/A₅₂₀) was proportional to the concentration of miR-378 (0.05–5 nM), with a detection limit of 0.05 nM. This method also has an evident detection effect on real samples. HeLa and L-02 cell extracts were analyzed using this method. The former showed no obvious color change, whereas the maximum absorption peak of the latter showed a red shift, and the color changed from red to purple. The minimum number of cells that could be detected using HeLa cells was 500 cells/mL. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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13 pages, 5542 KiB

Open AccessArticle

Bridging Blood and Skin: Biomarker Profiling in Dermal Interstitial Fluid (dISF) for Minimally Invasive Diagnostics

by Yann Sprunger, Johan Longo, Ali Saeidi and Adrian M. Ionescu

Biosensors 2025, 15(5), 301; https://doi.org/10.3390/bios15050301 - 9 May 2025

Viewed by 360

Abstract

Understanding the biochemical relationship between serum and dermal interstitial fluid (dISF) is critical for advancing minimally invasive diagnostics with wearables and point of care devices focusing on most relevant biomarkers accessible in the ISF. This work compares the composition of dISF and serum [...] Read more.

Understanding the biochemical relationship between serum and dermal interstitial fluid (dISF) is critical for advancing minimally invasive diagnostics with wearables and point of care devices focusing on most relevant biomarkers accessible in the ISF. This work compares the composition of dISF and serum using Xsensio’s microneedle-based collector, which yields an average of 3.4

μ

L/h. In the first study, total protein content, human serum albumin (HSA), and immunoglobulin G (IgG) are quantified in twelve volunteers. A second study is dedicated to screening 50 inflammation-related protein biomarkers across twenty volunteers. The results demonstrate that dISF closely resembles serum in its major protein constituents but at reduced concentrations (e.g., 57% for total protein). Strong correlations are observed between dISF and serum for CRP and SAA (

R^{2} > 0.87

), primarily driven by a subject with pathological levels, demonstrating the ability of dISF to reflect systemic inflammation. This study originally reports NT-proBNP detection at comparable levels in both fluids, suggesting that dISF could serve as a reliable proxy for blood NT-proBNP in the non-invasive diagnosis of cardiac failure. Cytokine profiling reveals 36 detectable cytokines, including several unique to dISF. Notably, interleukin concentrations are found to be highly similar between the two fluids. These experimental findings support dISF as a promising diagnostic medium for monitoring both localized and systemic biomarkers in clinical applications. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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18 pages, 4658 KiB

Open AccessArticle

Atomic Pt-Layer-Coated Au Peroxidase Nanozymes with Enhanced Activity for Ultrasensitive Colorimetric Immunoassay of Interleukin-12

by Han Zhang, Xiang Peng, Hao Song, Yongfeng Tan, Jianglian Xu, Qunfang Li and Zhuangqiang Gao

Biosensors 2025, 15(4), 239; https://doi.org/10.3390/bios15040239 - 9 Apr 2025

Viewed by 374

Abstract

Interleukin-12 (IL-12), a crucial biomarker for immune and inflammatory responses, plays a pivotal role in diagnosing and managing diverse pathological conditions. Although colorimetric enzyme-linked immunosorbent assays (CELISAs) have been extensively employed to detect IL-12 in biological samples, their sensitivity is inherently limited by [...] Read more.

Interleukin-12 (IL-12), a crucial biomarker for immune and inflammatory responses, plays a pivotal role in diagnosing and managing diverse pathological conditions. Although colorimetric enzyme-linked immunosorbent assays (CELISAs) have been extensively employed to detect IL-12 in biological samples, their sensitivity is inherently limited by the catalytic efficiency of enzyme labels, presenting substantial challenges in achieving ultrasensitive detection and enabling pre-symptomatic diagnosis of diseases. In this study, we address this limitation by developing a novel peroxidase nanozyme, featuring ultrathin Pt skins consisting of only ~4 atomic layers, coated on Au nanoparticles (denoted as Au@Pt_4LNPs). These Au@Pt_4LNPs exhibit remarkable catalytic performance, achieving a ~1063-fold enhancement in peroxidase-like activity compared to horseradish peroxidase (HRP), while minimizing Pt consumption, thereby improving Pt utilization efficiency and reducing costs. This advancement facilitates the construction of an ultrasensitive CELISA capable of detecting IL-12 at femtomolar concentrations. Using Au@Pt_4LNPs as the signal labels, the developed CELISA demonstrates a quantitative detection range from 0.1 to 100 pg mL⁻¹, with a limit of detection (LOD) as low as 0.084 pg mL⁻¹ (1.1 fM), offering ~10 times greater sensitivity than the HRP-based CELISA. This study highlights the potential of Au@Pt_4LNP nanozymes as advanced signal labels, opening new avenues for next-generation ultrasensitive bioassays. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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19 pages, 5726 KiB

Open AccessArticle

MOX Nanosensors to Detect Colorectal Cancer Relapses from Patient’s Blood at Three Years Follow-Up, and Gender Correlation

by Michele Astolfi, Giulia Zonta, Cesare Malagù, Gabriele Anania and Giorgio Rispoli

Biosensors 2025, 15(1), 56; https://doi.org/10.3390/bios15010056 - 16 Jan 2025

Cited by 1 | Viewed by 1081

Abstract

Colorectal cancer represents 10% of all the annual tumors diagnosed worldwide, being often not timely diagnosed, because its symptoms are typically lacking or very mild. Therefore, it is crucial to develop and validate innovative low-invasive techniques to detect it before becoming intractable. To [...] Read more.

Colorectal cancer represents 10% of all the annual tumors diagnosed worldwide, being often not timely diagnosed, because its symptoms are typically lacking or very mild. Therefore, it is crucial to develop and validate innovative low-invasive techniques to detect it before becoming intractable. To this aim, a device equipped with nanostructured gas sensors has been employed to detect the airborne molecules of blood samples collected from healthy subjects, and from colorectal cancer affected patients at different stages of their pre- and post-surgery therapeutic path. Data was scrutinized by using statistical standard techniques to highlight their statistical differences, and through principal component analysis and support vector machine to classify them. The device was able to readily distinguish between the pre-surgery blood samples (i.e., taken when the patient had cancer), and the ones up to three years post-surgery (i.e., following the tumor removal) or the ones from healthy subjects. Finally, the correlation of the sensor responses with the patient/healthy subject’s gender was investigated, resulting negligible. These results pave the path toward a clinical validation of this device to monitor the patient’s health status by detecting possible relapses, to parallel to clinical follow-up protocols. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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13 pages, 3759 KiB

Open AccessArticle

An MSRE-Assisted Glycerol-Enhanced RPA-CRISPR/Cas12a Method for Methylation Detection

by Zhiquan Lu, Zilu Ye, Ping Li, Yike Jiang, Sanyang Han and Lan Ma

Biosensors 2024, 14(12), 608; https://doi.org/10.3390/bios14120608 - 12 Dec 2024

Cited by 1 | Viewed by 1217

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor with high prevalence in southern China. Aberrant DNA methylation, as a hallmark of cancer, is extensively present in NPC, the detection of which facilitates early diagnosis and prognostic improvement of NPC. Conventional methylation detection methods [...] Read more.

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor with high prevalence in southern China. Aberrant DNA methylation, as a hallmark of cancer, is extensively present in NPC, the detection of which facilitates early diagnosis and prognostic improvement of NPC. Conventional methylation detection methods relying on bisulfite conversion have limitations such as time-consuming, complex processes and sample degradation; thus, a more rapid and efficient method is needed. Methods: We propose a novel DNA methylation assay based on methylation-sensitive restriction endonuclease (MSRE) HhaI digestion and Glycerol-enhanced recombinase polymerase amplification (RPA)-CRISPR/Cas12a detection (HGRC). MSRE has a fast digestion rate, and HhaI specifically cleaves unmethylated DNA at a specific locus, leaving the methylated target intact to trigger the downstream RPA-Cas12a detection step, generating a fluorescence signal. Moreover, the detection step was supplemented with glycerol for the separation of Cas12a-containing components and RPA- and template-containing components, which avoids over-consumption of the template and, thus, enhances the amplification efficiency and detection sensitivity. Results: The HGRC method exhibits excellent performance in the detection of a CNE2-specific methylation locus with a (limit of detection) LOD of 100 aM and a linear range of 100 aM to 100 fM. It also responds well to different methylation levels and is capable of distinguishing methylation levels as low as 0.1%. Moreover, this method can distinguish NPC cells from normal cells by detecting methylation in cellular genomes. This method provides a rapid and sensitive approach for NPC detection and also holds good application prospects for other cancers and diseases featuring DNA methylation as a biomarker. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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15 pages, 7613 KiB

Open AccessArticle

Electrochemical Analysis of Amyloid Plaques and ApoE4 with Chitosan-Coated Gold Nanostars for Alzheimer’s Detection

by Min-Kyung Shin, Ariadna Schuck, Minhee Kang and Yong-Sang Kim

Biosensors 2024, 14(10), 510; https://doi.org/10.3390/bios14100510 - 17 Oct 2024

Cited by 2 | Viewed by 1781

Abstract

Monitoring the progression of Alzheimer’s disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is [...] Read more.

Monitoring the progression of Alzheimer’s disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is hindered by the blood–brain barrier (BBB), resulting in lower concentrations. To address this challenge and identify pertinent AD biomarkers—specifically amyloid plaques and apolipoprotein E4 (ApoE4)—in blood plasma, we propose an innovative approach. This involves enhancing a screen-printed carbon electrode (SPCE) with an immobilization matrix comprising gold nanostars (AuNSs) coated with chitosan. Morphological and electrical analyses confirmed superior dispersion and conductivity with 0.5% chitosan, supported by UV–Vis spectroscopy, cyclic voltammetry, and Nyquist plots. Subsequent clinical assays measured electrical responses to quantify amyloid-β 42 (Aβ42) (15.63–1000 pg/mL) and APoE4 levels (0.41 to 40 ng/mL) in human blood plasma samples. Differential pulse voltammetry (DPV) responses exhibited peak currents proportional to biomarker concentrations, demonstrating high linear correlations (0.985 for Aβ42 and 0.919 for APoE4) with minimal error bars. Cross-reactivity tests with mixed solutions of amyloid-β 40 (Aβ40), Aβ42, and ApoE4 indicated minimal interference between biomarkers (<3% variation), further confirming the high specificity of the developed sensor. Validation studies demonstrated a strong concurrence with the gold-standard enzyme-linked immunosorbent assay (ELISA), while interference tests indicated a minimal variation in peak currents. This improved device presents promising potential as a point-of-care system, offering a less invasive, cost-effective, and simplified approach to detecting and tracking the progression of AD. The substantial surface binding area further supports the efficacy of our method, offering a promising avenue for advancing AD diagnostics. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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11 pages, 5333 KiB

Open AccessArticle

Fluorescence Immunoassay of Prostate-Specific Antigen Using 3D Paddle Screw-Type Devices and Their Rotating System

by Su Bin Han, Han Sol Kim, Young Ju Jo and Soo Suk Lee

Biosensors 2024, 14(10), 494; https://doi.org/10.3390/bios14100494 - 11 Oct 2024

Viewed by 1430

Abstract

In this paper, we present a sensitive and highly reproducible fluorescence immunosensor for detecting PSA in human serum. A unique feature of this study is that it uses creatively designed paddle screw-type devices and their custom-made rotating system for PSA immunoassay. The paddle [...] Read more.

In this paper, we present a sensitive and highly reproducible fluorescence immunosensor for detecting PSA in human serum. A unique feature of this study is that it uses creatively designed paddle screw-type devices and their custom-made rotating system for PSA immunoassay. The paddle screw devices were designed to maximize the surface-to-volume ratio over which the immunoassay reaction could occur to improve detection sensitivity. This paddle screw-based immunoassay offers an accessible and efficient method with a short analysis time of less than 30 min. Active rotation of the paddle screw plays a crucial role in fast and accurate analysis of PSA. Additionally, a paddle screw-based immunoassay and subsequent fluorescence detection using a custom prototype fluorescence detection system were compared to a typical well plate-based immunoassay system. Results of PSA detection in human serum showed that the detection sensitivity through the paddle screw-based analysis improved about five times compared to that with a well plate-based analysis. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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13 pages, 3048 KiB

Open AccessArticle

Paper-Based DNA Biosensor for Rapid and Selective Detection of miR-21

by Alexander Hunt, Sri Ramulu Torati and Gymama Slaughter

Biosensors 2024, 14(10), 485; https://doi.org/10.3390/bios14100485 - 8 Oct 2024

Cited by 4 | Viewed by 2449

Abstract

Cancer is the second leading cause of death globally, with 9.7 million fatalities in 2022. While routine screenings are vital for early detection, healthcare disparities persist, highlighting the need for equitable solutions. Recent advancements in cancer biomarker identification, particularly microRNAs (miRs), have improved [...] Read more.

Cancer is the second leading cause of death globally, with 9.7 million fatalities in 2022. While routine screenings are vital for early detection, healthcare disparities persist, highlighting the need for equitable solutions. Recent advancements in cancer biomarker identification, particularly microRNAs (miRs), have improved early detection. MiR-21 is notably overexpressed in various cancers and can be a valuable diagnostic tool. Traditional detection methods, though accurate, are costly and complex, limiting their use in resource-limited settings. Paper-based electrochemical biosensors offer a promising alternative, providing cost-effective, sensitive, and rapid diagnostics suitable for point-of-care use. This study introduces an innovative electrochemical paper-based biosensor that leverages gold inkjet printing for the quantitative detection of miR-21. The biosensor, aimed at developing cost-effective point-of-care devices for low-resource settings, uses thiolated self-assembled monolayers to immobilize single-stranded DNA-21 (ssDNA-21) on electrodeposited gold nanoparticles (AuNPs) on the printed gold surface, facilitating specific miR-21 capture. The hybridization of ssDNA-21 with miR-21 increases the anionic barrier density, impeding electron transfer from the redox probe and resulting in a current suppression that correlates with miR-21 concentration. The biosensor exhibited a linear detection range from 1 fM to 1 nM miR-21 with a sensitivity of 7.69 fM µA⁻¹ cm² and a rapid response time (15 min). With a low detection limit of 0.35 fM miR-21 in serum, the biosensor also demonstrates excellent selectivity against interferent species. This study introduces an electrochemical paper-based biosensor that uses gold inkjet printing to precisely detect miR-21, a key biomarker overexpressed in various cancers. This innovative device highlights the potential for cost-effective, accessible cancer diagnostics in underserved areas. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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Review

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19 pages, 885 KiB

Open AccessReview

Piezoelectric Chemosensors and Biosensors in Medical Diagnostics

by Miroslav Pohanka

Biosensors 2025, 15(3), 197; https://doi.org/10.3390/bios15030197 - 20 Mar 2025

Viewed by 2602

Abstract

This article explores the development and application of innovative piezoelectric sensors in point-of-care diagnostics. It highlights the significance of bedside tests, such as lateral flow and electrochemical tests, in providing rapid and accurate results directly at the patient’s location. This paper delves into [...] Read more.

This article explores the development and application of innovative piezoelectric sensors in point-of-care diagnostics. It highlights the significance of bedside tests, such as lateral flow and electrochemical tests, in providing rapid and accurate results directly at the patient’s location. This paper delves into the principles of piezoelectric assays, emphasizing their ability to detect disease-related biomarkers through mechanical stress-induced electrical signals. Various applications of piezoelectric chemosensors and biosensors are discussed, including their use in the detection of cancer biomarkers, pathogens, and other health-related analytes. This article also addresses the integration of piezoelectric materials with advanced sensing technologies to improve diagnostic accuracy and efficiency, offering a comprehensive overview of current advances and future directions in medical diagnostics. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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23 pages, 3427 KiB

Open AccessReview

Development of Neurodegenerative Disease Diagnosis and Monitoring from Traditional to Digital Biomarkers

by Jaeyoon Song, Eunseo Cho, Huiseop Lee, Suyoung Lee, Sehyeon Kim and Jinsik Kim

Biosensors 2025, 15(2), 102; https://doi.org/10.3390/bios15020102 - 11 Feb 2025

Cited by 1 | Viewed by 1692

Abstract

Monitoring and assessing the progression of symptoms in neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are critical for improving patient outcomes. Traditional biomarkers, such as cerebrospinal fluid analysis and brain imaging, are widely used to investigate the underlying mechanisms of disease and enable [...] Read more.

Monitoring and assessing the progression of symptoms in neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are critical for improving patient outcomes. Traditional biomarkers, such as cerebrospinal fluid analysis and brain imaging, are widely used to investigate the underlying mechanisms of disease and enable early diagnosis. In contrast, digital biomarkers derived from phenotypic changes—such as EEG, eye movement, gait, and speech analysis—offer a noninvasive and accessible alternative. Leveraging portable and widely available devices, such as smartphones and wearable sensors, digital biomarkers are emerging as a promising tool for ND diagnosis and monitoring. This review highlights the comprehensive developments in digital biomarkers, emphasizing their unique advantages and integration potential alongside traditional biomarkers. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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14 pages, 1032 KiB

Open AccessReview

Needle-Shaped Biosensors for Precision Diagnoses: From Benchtop Development to In Vitro and In Vivo Applications

by Ruier Xue, Fei Deng, Tianruo Guo, Alexander Epps, Nigel H. Lovell and Mohit N. Shivdasani

Biosensors 2024, 14(8), 391; https://doi.org/10.3390/bios14080391 - 13 Aug 2024

Viewed by 2351

Abstract

To achieve the accurate recognition of biomarkers or pathological characteristics within tissues or cells, in situ detection using biosensor technology offers crucial insights into the nature, stage, and progression of diseases, paving the way for enhanced precision in diagnostic approaches and treatment strategies. [...] Read more.

To achieve the accurate recognition of biomarkers or pathological characteristics within tissues or cells, in situ detection using biosensor technology offers crucial insights into the nature, stage, and progression of diseases, paving the way for enhanced precision in diagnostic approaches and treatment strategies. The implementation of needle-shaped biosensors (N-biosensors) presents a highly promising method for conducting in situ measurements of clinical biomarkers in various organs, such as in the brain or spinal cord. Previous studies have highlighted the excellent performance of different N-biosensor designs in detecting biomarkers from clinical samples in vitro. Recent preclinical in vivo studies have also shown significant progress in the clinical translation of N-biosensor technology for in situ biomarker detection, enabling highly accurate diagnoses for cancer, diabetes, and infectious diseases. This article begins with an overview of current state-of-the-art benchtop N-biosensor designs, discusses their preclinical applications for sensitive diagnoses, and concludes by exploring the challenges and potential avenues for next-generation N-biosensor technology. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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19 pages, 5361 KiB

Open AccessReview

Aptamer Screening: Current Methods and Future Trend towards Non-SELEX Approach

by Zhihui Fang, Xiaorui Feng, Fan Tang, Han Jiang, Shuyuan Han, Ran Tao and Chenze Lu

Biosensors 2024, 14(7), 350; https://doi.org/10.3390/bios14070350 - 18 Jul 2024

Cited by 8 | Viewed by 3724

Abstract

Aptamers are nucleic acid sequences that specifically bind with target molecules and are vital to applications such as biosensing, drug development, disease diagnostics, etc. The traditional selection procedure of aptamers is based on the Systematic Evolution of Ligands by an Exponential Enrichment (SELEX) [...] Read more.

Aptamers are nucleic acid sequences that specifically bind with target molecules and are vital to applications such as biosensing, drug development, disease diagnostics, etc. The traditional selection procedure of aptamers is based on the Systematic Evolution of Ligands by an Exponential Enrichment (SELEX) process, which relies on repeating cycles of screening and amplification. With the rapid development of aptamer applications, RNA and XNA aptamers draw more attention than before. But their selection is troublesome due to the necessary reverse transcription and transcription process (RNA) or low efficiency and accuracy of enzymes for amplification (XNA). In light of this, we review the recent advances in aptamer selection methods and give an outlook on future development in a non-SELEX approach, which simplifies the procedure and reduces the experimental costs. We first provide an overview of the traditional SELEX methods mostly designed for screening DNA aptamers to introduce the common tools and methods. Then a section on the current screening methods for RNA and XNA is prepared to demonstrate the efforts put into screening these aptamers and the current difficulties. We further predict that the future trend of aptamer selection lies in non-SELEX methods that do not require nucleic acid amplification. We divide non-SELEX methods into an immobilized format and non-immobilized format and discuss how high-resolution partitioning methods could facilitate the further improvement of selection efficiency and accuracy. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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