scholarly journals Isolating Specific vs. Non-Specific Binding Responses in Conducting Polymer Biosensors for Bio-Fingerprinting

Sensors ◽  
2021 ◽  
Vol 21 (19) ◽  
pp. 6335
Author(s):  
Phil M. Smith ◽  
Indorica Sutradhar ◽  
Maxwell Telmer ◽  
Rishikesh Magar ◽  
Amir Barati Farimani ◽  
...  
Keyword(s):  
Conducting Polymer ◽  
Specific Binding ◽  
Signal To Noise Ratio ◽  
Label Free ◽  
Nonspecific Binding ◽  
Complex Samples ◽  
Learning Classifier ◽  
Analyte Solution ◽  
Sensitivity Specificity ◽  
The Cost

A longstanding challenge for accurate sensing of biomolecules such as proteins concerns specifically detecting a target analyte in a complex sample (e.g., food) without suffering from nonspecific binding or interactions from the target itself or other analytes present in the sample. Every sensor suffers from this fundamental drawback, which limits its sensitivity, specificity, and longevity. Existing efforts to improve signal-to-noise ratio involve introducing additional steps to reduce nonspecific binding, which increases the cost of the sensor. Conducting polymer-based chemiresistive biosensors can be mechanically flexible, are inexpensive, label-free, and capable of detecting specific biomolecules in complex samples without purification steps, making them very versatile. In this paper, a poly (3,4-ethylenedioxyphene) (PEDOT) and poly (3-thiopheneethanol) (3TE) interpenetrating network on polypropylene–cellulose fabric is used as a platform for a chemiresistive biosensor, and the specific and nonspecific binding events are studied using the Biotin/Avidin and Gliadin/G12-specific complementary binding pairs. We observed that specific binding between these pairs results in a negative ΔR with the addition of the analyte and this response increases with increasing analyte concentration. Nonspecific binding was found to have the opposite response, a positive ΔR upon the addition of analyte was seen in nonspecific binding cases. We further demonstrate the ability of the sensor to detect a targeted protein in a dual-protein analyte solution. The machine-learning classifier, random forest, predicted the presence of Biotin with 75% accuracy in dual-analyte solutions. This capability of distinguishing between specific and nonspecific binding can be a step towards solving the problem of false positives or false negatives to which all biosensors are susceptible.

scholarly journals 3D phonon microscopy with sub-micron axial-resolution

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard J. Smith ◽  
Fernando Pérez-Cota ◽  
Leonel Marques ◽  
Matt Clark
Keyword(s):  
Signal To Noise Ratio ◽  
Single Cells ◽  
Optical Resolution ◽  
Acquisition Time ◽  
Label Free ◽  
Axial Resolution ◽  
Force Microscopy ◽  
Atomic Force ◽  
Accuracy And Precision ◽  
Good Agreement

AbstractBrillouin light scattering (BLS) is an emerging method for cell imaging and characterisation. It allows elasticity-related contrast, optical resolution and label-free operation. Phonon microscopy detects BLS from laser generated coherent phonon fields to offer an attractive route for imaging since, at GHz frequencies, the phonon wavelength is sub-optical. Using phonon fields to image single cells is challenging as the signal to noise ratio and acquisition time are often poor. However, recent advances in the instrumentation have enabled imaging of fixed and living cells. This work presents the first experimental characterisation of phonon-based axial resolution provided by the response to a sharp edge. The obtained axial resolution is up to 10 times higher than that of the optical system used to take the measurements. Validation of the results are obtained with various polymer objects, which are in good agreement with those obtained using atomic force microscopy. Edge localisation, and hence profilometry, of a phantom boundary is measured with accuracy and precision of approximately 60 nm and 100 nm respectively. Finally, 3D imaging of fixed cells in culture medium is demonstrated.

scholarly journals Microfluidic Impedance Biosensor Chips Using Sensing Layers Based on DNA-Based Self-Assembled Monolayers for Label-Free Detection of Proteins

Biosensors ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 80
Author(s):  
Khaled Alsabbagh ◽  
Tim Hornung ◽  
Achim Voigt ◽  
Sahba Sadir ◽  
Taleieh Rajabi ◽  
...  
Keyword(s):  
Troponin I ◽  
Electrochemical Impedance ◽  
Specific Binding ◽  
Self Assembled Monolayers ◽  
Significant Shift ◽  
Label Free ◽  
Label Free Detection ◽  
Assembled Monolayers ◽  
Self Assembled ◽  
Biosensor Chip

A microfluidic chip for electrochemical impedance spectroscopy (EIS) is presented as bio-sensor for label-free detection of proteins by using the example of cardiac troponin I. Troponin I is one of the most specific diagnostic serum biomarkers for myocardial infarction. The microfluidic impedance biosensor chip presented here consists of a microscope glass slide serving as base plate, sputtered electrodes, and a polydimethylsiloxane (PDMS) microchannel. Electrode functionalization protocols were developed considering a possible charge transfer through the sensing layer, in addition to analyte-specific binding by corresponding antibodies and reduction of nonspecific protein adsorption to prevent false-positive signals. Reagents tested for self-assembled monolayers (SAMs) on gold electrodes included thiolated hydrocarbons and thiolated oligonucleotides, where SAMs based on the latter showed a better performance. The corresponding antibody was covalently coupled on the SAM using carbodiimide chemistry. Sampling and measurement took only a few minutes. Application of a human serum albumin (HSA) sample, 1000 ng/mL, led to negligible impedance changes, while application of a troponin I sample, 1 ng/mL, led to a significant shift in the Nyquist plot. The results are promising regarding specific detection of clinically relevant concentrations of biomarkers, such as cardiac markers, with the newly developed microfluidic impedance biosensor chip.

scholarly journals Label-Free Mass Spectrometry-Based Quantification of Linker Histone H1 Variants in Clinical Samples

2020 ◽  
Vol 21 (19) ◽  
pp. 7330
Author(s):  
Roberta Noberini ◽  
Cristina Morales Torres ◽  
Evelyn Oliva Savoia ◽  
Stefania Brandini ◽  
Maria Giovanna Jodice ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Histone H1 ◽  
Histone Variants ◽  
Linker Histone ◽  
Clinical Samples ◽  
Label Free ◽  
Complex Samples ◽  
Linker Histone H1 ◽  
Ideal Tool ◽  
Free Quantification

Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally histone H1 levels have been studied using antibody-based methods and RNA expression, these approaches suffer from limitations. Mass spectrometry (MS)-based proteomics represents the ideal tool to accurately quantify relative changes in protein abundance within complex samples. In this study, we used a label-free quantification approach to simultaneously analyze all somatic histone H1 variants in clinical samples and verified its applicability to laser micro-dissected tissue areas containing as low as 1000 cells. We then applied it to breast cancer patient samples, identifying differences in linker histone variants patters in primary triple-negative breast tumors with and without relapse after chemotherapy. This study highlights how label-free quantitation by MS is a valuable option to accurately quantitate histone H1 levels in different types of clinical samples, including very low-abundance patient tissues.

Median Morphological Filter Design Based on the PSO Algorithm

2011 ◽  
Vol 128-129 ◽  
pp. 181-184
Author(s):  
You Lian Zhu ◽  
Cheng Huang
Keyword(s):  
Filter Design ◽  
Design Method ◽  
Signal To Noise Ratio ◽  
Pso Algorithm ◽  
Morphological Operations ◽  
Morphological Filter ◽  
Signal To Noise ◽  
Noise Ratio ◽  
The Cost ◽  
Filter Design Method

Design of morphological filter greatly depends on morphological operations and structuring elements selection. A filter design method used median closing morphological operation is proposed to enhance the image denoising ability and the PSO algorithm is introduced for structural elements selecting. The method takes the peak value signal-to-noise ratio (PSNR) as the cost function and may adaptively build unit structuring elements with zero square matrix. Experimental results show the proposed method can effectively remove impulse noise from a noisy image, especially from a low signal-to-noise ratio (SNR) image; the noise reduction performance has obvious advantages than the other.

Label-free detection of kanamycin based on the aptamer-functionalized conducting polymer/gold nanocomposite

2012 ◽  
Vol 36 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Ye Zhu ◽  
Pranjal Chandra ◽  
Kyung-Mi Song ◽  
Changill Ban ◽  
Yoon-Bo Shim
Keyword(s):  
Conducting Polymer ◽  
Label Free ◽  
Label Free Detection

Systematic Optimisation of Microtiter Plate Lectin Assay to Improve Sialic Acid Linkage Detection

2021 ◽  
Vol 24 ◽  
Author(s):  
Nur Hanina Izzati Khairol Mokhtar ◽  
Ainulkhir Hussin ◽  
Aidil Abdul Hamid ◽  
Shahrul Hisham Zainal Ariffin ◽  
Muhammad Ashraf Shahidan
Keyword(s):  
Sialic Acid ◽  
Specific Binding ◽  
Specific Antigen ◽  
Blocking Agent ◽  
Microtiter Plate ◽  
Tween 20 ◽  
Nonspecific Binding ◽  
Binding Assays ◽  
High Background ◽  
Sialic Acid Linkage

Aims: We aimed to develop a high-throughput lectin assay with minimized background signals to investigate the interactions of lectins and sialic acid glycans, focusing on prostate-specific antigen (PSA). Background: High background signals resulting from nonspecific binding are a significant concern for microtiter plate-based enzyme-linked lectin sorbent assays (ELLSAs), as they can mask specific binding signals and cause false-positive results. Methods: In this study, we constructed an ELLSA based on different washing step parameters, including the number of washing cycles, NaCl and Tween-20 concentrations, and the type of blocking agent and evaluated the effects on both specific and nonspecific binding signals. Furthermore, we performed a PSA binding assay using the optimized ELLSA. Results: The optimal washing parameters based on the highest specific binding signal proposed four cycles of washing steps using a washing buffer containing a high salt concentration (0.5 M NaCl) and mild detergent (0.05% Tween-20). The utilization of the optimized washing parameters in this assay was shown to be sufficient to obtain the optimal binding signals without the use of any blocking agent. Binding assays performed using the optimized ELLSA revealed that the glycan of the PSA sample used in this study mainly consists of terminal α2,6-linked sialic acid, as strongly recognized by Sambucus nigra agglutinin (SNA) with a KD value of 12.38 nM. Conclusion: The ELLSA reported in this study provides a simple yet sensitive assay for sialic acid linkage recognition.

scholarly journals Facilitating Institutional Oversight and Program Improvement Through Educational Competency Committees

2016 ◽  
Vol 8 (3) ◽  
pp. 384-389 ◽  
Author(s):  
Kathryn M. Andolsek ◽  
Rhea F. Fortune ◽  
Alisa Nagler ◽  
Chrystal Stancil ◽  
Catherine Kuhn ◽  
...  
Keyword(s):  
Professional Development ◽  
Best Practices ◽  
Predictive Value ◽  
Program Improvement ◽  
Total Cost ◽  
Program Evaluations ◽  
Special Review ◽  
Sensitivity Specificity ◽  
The Cost ◽  
Institutional Oversight

ABSTRACT  The Accreditation Council for Graduate Medical Education (ACGME) requires programs to engage annually in program evaluation and improvement.Background  We assessed the value of creating educational competency committees (ECCs) that use successful elements of 2 established processes—institutional special reviews and institutional oversight of annual program evaluations.Objective  The ECCs used a template to review programs' annual program evaluations. Results were aggregated into an institutional dashboard. We calculated the costs, sensitivity, specificity, and predictive value by comparing programs required to have a special review with those that had ACGME citations, requests for a progress report, or a data-prompted site visit. We assessed the value for professional development through a participant survey.Methods  Thirty-two ECCs involving more than 100 individuals reviewed 237 annual program evaluations over a 3-year period. The ECCs required less time than internal reviews. The ECCs rated 2 to 8 programs (2.4%–9.8%) as “noncompliant.” One to 13 programs (1.2%–14.6%) had opportunities for improvement identified. Institutional improvements were recognized using the dashboard. Zero to 13 programs (0%–16%) were required to have special reviews. The sensitivity of the decision to have a special review was 83% to 100%; specificity was 89% to 93%; and negative predictive value was 99% to 100%. The total cost was $280 per program. Of the ECC members, 86% to 95% reported their participation enhanced their professional development, and 60% to 95% believed the ECC benefited their program.Results  Educational competency committees facilitated the identification of institution-wide needs, highlighted innovation and best practices, and enhanced professional development. The cost, sensitivity, specificity, and predictive value indicated good value.Conclusions

slowly growing natural populations. Various approaches have been adopted in order to improve the sensitivity. These have included the use of multiple probes labelled with a single fluor (Lee et al. 1993); or labelled with multiple fluors (Trebesius et al. 1994) and enzyme-linked probes or detection systems that allow signal amplification (Lebaron et al. 1997, Schonhuber et al. 1999). The latter indirect approach not only has the potential for signal amplification, but may also be used in natural samples showing high levels of autofluorescence. Any thorough identification method has to include positive and negative controls. False-positive results may either be caused by cells emitting autofluorescence upon excitation or by nonspecific binding of the probe to nontarget cells. Samples should therefore be checked for autofluorescence before hybridization and a negative control with a fluorescent oligonucleotide not complementary to rRNA has to be applied to check for sequence-independent nonspecific binding. Such non-specific binding may be due to interaction of the dye compound of the probe with hydrophobic cell components. Failures to detect cells containing target sequences (false-negatives) may originate from cells with either low cellular ribosome content or limited permeability of the cell periphery for the fluorescent probe (Manz et al. 1992). With the rapidly expanding database of 16S rRNA sequences, the problem of probe specificity has become more apparent and the design of probes is becoming increasingly difficult. These problems are also applicable to PCR and other oligonucleotide-dependent techniques. The problem of probe specificity may be overcome by using multiple specific oligonucleotide probes targeting different sites on the rRNA molecule and labelled with different fluorochromes. While a single oligonucleotide target sequence may be found in a number of related taxa, the probability that target sites for three designed oligonucleotides are found in a nontarget organism is, however, much reduced.

2003 ◽  
pp. 232-232
Keyword(s):  
Signal Amplification ◽  
Specific Binding ◽  
Natural Populations ◽  
Negative Control ◽  
Target Sequence ◽  
Cell Periphery ◽  
Nonspecific Binding ◽  
Detection Systems ◽  
Cell Components ◽  
Negative Controls

Conducting Polymer Nanowire-Based BioFET for Label-Free Detection

2006 ◽  
pp. 133-150
Author(s):  
Wilfred Chen ◽  
Ashok Mulchandani ◽  
Nosang Myung ◽  
Adam Wanekaya
Keyword(s):  
Conducting Polymer ◽  
Label Free ◽  
Label Free Detection

Multichannel absorption compensation with a data-driven structural regularization

Geophysics ◽  
2019 ◽  
Vol 85 (1) ◽  
pp. V71-V80 ◽  
Author(s):  
Xiong Ma ◽  
Guofa Li ◽  
Hao Li ◽  
Wuyang Yang
Keyword(s):  
Cost Function ◽  
Structural Characteristic ◽  
Seismic Data ◽  
High Frequency ◽  
Signal To Noise Ratio ◽  
Random Noise ◽  
Frequency Noise ◽  
Characteristic Operator ◽  
High Frequency Noise ◽  
The Cost

Seismic absorption compensation is an important processing approach to mitigate the attenuation effects caused by the intrinsic inelasticity of subsurface media and to enhance seismic resolution. However, conventional absorption compensation approaches ignore the spatial connection along seismic traces, which makes the compensation result vulnerable to high-frequency noise amplification, thus reducing the signal-to-noise ratio (S/N) of the result. To alleviate this issue, we have developed a structurally constrained multichannel absorption compensation (SC-MAC) algorithm. In the cost function of this algorithm, we exploit an [Formula: see text] norm to constrain the reflectivity series and an [Formula: see text] norm to regularize the reflection structural characteristic of the compensation data. The reflection structural characteristic operator, extracted from the observed stacked seismic data, is the core of the structural regularization term. We then solve the cost function of SC-MAC by the alternating direction method of multipliers. Benefiting from the introduction of reflection structure constraint, SC-MAC improves the stability of the compensation result and inhibits the amplification of high-frequency noise. Synthetic and field data examples demonstrate that our proposed method is more robust to random noise and can not only improve the resolution of seismic data, but also maintain the S/N of the compensation seismic data.

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