General notes for selection

• ***Advances and challenges in small-molecule DNA aptamer isolation, characterization, and sensor development (long review) : https://doi.org/10.1002/anie.202008663 

• Aptamer selection using capture-SELEX (e.g, protocol, library, etc) : www.sciencedirect.com/science/article/abs/pii/S1046202316301220, https://www.science.org/doi/10.1126/science.abn9859

• Aptamers are sensitive to ionic strength, which directly affects their ability to adopt the correct tertiary structure. Therefore, buffer conditions should be chosen to closely match those of the intended application. The applied selection pressure is critical. Even for the same ligand, different selection conditions can yield distinct aptamers.

• Library length is also important, some time only a specific length library contains the functional sequence (affinity/selectivity) : https://pubs.acs.org/doi/10.1021/acscentsci.4c01377, https://www.science.org/doi/10.1126/science.abn9859, https://doi.org/10.1002/anie.202318665 

• Capture sequence composition is important to induce structure-switching/functional aptamer: Fig. S61 https://www.science.org/doi/10.1126/science.abn9859

• Improved capture kinetic release (increased time incubation) : https://onlinelibrary.wiley.com/doi/10.1002/anie.202514445

• Hybridization efficiency and hybridization stability to the capture strand : https://doi.org/10.1021/acs.biochem.5c00778

• Selection strategies: standard, target derivatization/complexation https://www.nature.com/articles/nchem.2058, N8 scaffold for TWJ receptors https://pubs.acs.org/doi/10.1021/ja2084256, functional group based approach https://www.science.org/doi/10.1126/science.abn9859.

• Ligand binding should not be assumed to proceed via displacement or release mechanisms; aptamer structural switching can follow a range of alternative pathways : Fig. 4 https://pubs.acs.org/doi/10.1021/acssensors.8b00516

Microfluidic-assisted selection

• Microfluidic-based aptamer selection platforms can be broadly categorized into on-chip and off-chip designs. In fully integrated on-chip systems, key steps such as target binding, partitioning, concentration, and PCR amplification of selected binders are performed within the microfluidic device. Alternatively, hybrid approaches use microfluidics for selection and enrichment, while amplification and processing steps (e.g., PCR) are carried out off-chip using conventional laboratory equipment.

• Aptamer selection via microfluidic platforms and their diverse applications : https://doi.org/10.1039/d4lc00859f

• Microfluidic platform for efficient screening of advanced glycation end products aptamer : https://doi.org/10.1016/j.bios.2024.117038

• Dynamic selection of high-affinity aptamers using a magnetically activated continuous deflection microfluidic chip : https://doi.org/10.1039/D4CC00229F

• A high-dimensional microfluidic approach for selection of aptamers with programmable binding affinities : https://doi.org/10.1038/s41557-023-01207-z

• Microfluidic methods for aptamer selection and characterization : https://doi.org/10.1039/C7AN01046J

General notes for screening

• Sequencing result analysis : fastaptamer2.missouri.edu/

• Sequence aligment : http://multalin.toulouse.inra.fr/multalin/example.html

• G-quadruplex prediction : https://bioinformatics.ramapo.edu/QGRS/index.php

• Secondary structure prediction : www.unafold.org/mfold/applications/dna-folding-form.php , nupack.org/ 

• Initial screening using the dye/strand displacement assay (detailed protocol) :  www.science.org/doi/10.1126/science.abn9859 

• Eps2Fold: a rapid method to characterize G-quadruplex DNA structures using single absorbance spectra : https://academic.oup.com/nar/article/53/18/gkaf953/8267757

• UT Austin aptamer database (over 1,400 aptamers) : sites.utexas.edu/aptamerdatabase/ 

Solution-based techniques : A range of solution-based techniques can be used to characterize aptamers, including determining binding affinity and thermodynamic parameters, as well as verifying whether they undergo structural changes upon ligand recognition, as expected from capture-SELEX-derived aptamers. A combination of complementary techniques is highly recommended.

• ***Widespread omission of aptamer-target binding verification in aptasensor development : https://chemrxiv.org/doi/full/10.26434/chemrxiv.15001564/v1

• ***Solution-based biophysical characterization of conformation change in structure-switching aptamers (technique review) : doi.org/10.1017/S0033583524000076 

• ***A roadmap for reliable determination of aptamer−target equilibrium dissociation constants : https://doi.org/10.1021/acssensors.6c00130

• Isothermal titration calorimetry (summary, explanation, experiment design for non-experts) : japtamers.co.uk/isothermal-titration-calorimetry-studies-of-aptamer-small-molecule-interactions-practicalities-and-pitfalls/  

• Nuclear resonance magnetic spectroscopy (experimental guide for non-experts) : japtamers.co.uk/wp-content/uploads/2020/11/Churcher.pdf 

• Circular dischroism spectroscopy : https://link.springer.com/protocol/10.1007/978-1-0716-2695-5_9

• Fluorescence polarization : https://pubs.acs.org/doi/10.1021/jacs.2c00478

• FRET : https://www.science.org/doi/10.1126/science.aao6750, review https://doi.org/10.1002/anie.202207188

Surface-based techniques are also used to characterize the aptamer binding kinetics when tethered on surface

• Redox-based approach such as electrochemical impedance spectroscopy allows to monitor the binding-induced electron transfer rate: https://doi.org/10.1016/j.bios.2024.116680

• Surface plasmon resonance : directly attached aptamer https://pubs.acs.org/doi/10.1021/acs.analchem.2c04192, competitive assay format https://pubs.acs.org/doi/10.1021/acs.analchem.4c04120, splitting aptamer format https://doi.org/10.1039/D4AN01226G

• Bio-layer interferometry : https://pubs.acs.org/doi/10.1021/acssensors.3c02004

• Quartz crystal microbalance with dissipation monitoring : https://pubs.acs.org/doi/10.1021/acsnano.3c05377

• Fluorescent assay combined with microfluidic system : https://pubs.acs.org/doi/10.1021/acsnano.5c19596

• Binding site mapping : https://www.nature.com/articles/s41565-023-01591-0, https://pubs.acs.org/doi/10.1021/jacsau.3c00781

• Sequence trimming/truncation : exonuclease assay, docking

• Mismatch based design to tune the signaling magnitude and sensitivity : https://doi.org/10.1002/anse.202500077

• Circular permutation : https://pubs.acs.org/doi/10.1021/jacsau.3c00781, https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000729/v1, https://pmc.ncbi.nlm.nih.gov/articles/PMC3866043/

• Insertion-(re)selection : https://www.science.org/doi/10.1126/science.abn9859, https://pubs.acs.org/doi/10.1021/jacsau.3c00781

• Motif SELEX : https://pubs.acs.org/doi/full/10.1021/jacs.4c17041

• Spilitting aptamer (not really generalizable to many aptamers and splitting ability is structure-dependent) : https://pubs.rsc.org/en/content/articlelanding/2025/an/d4an01226g

• Modular aptamer switch design : https://doi.org/10.1002/adma.202304410, fluorescent modification https://doi.org/10.1093/nar/gkaf1346

• Structure-guided dimer assembly to improve binding affinity : https://doi.org/10.1021/acs.analchem.6c00265

Suggested signaling mechanisms

• Binding-induced changes in electron transfer rate : https://doi.org/10.1002/elan.200804564

• Redox-ligand competition (MN19 aptamer) : https://doi.org/10.1002/chem.202300618

Aptamer adaptation strategies

In general, the SELEX-derived original aptamers should be re-designed to adapt to the electrode surface. Many strategies would be used to re-engineering the aptamers. Truncation is the most generabilizable approach but there are still other techniques that would enable functional sensors when rationnally employed.

• Truncation and antisense design : https://pmc.ncbi.nlm.nih.gov/articles/PMC3866043/

• Allosteric inhibitor: https://pubs.acs.org/doi/10.1021/ja304672h

• Mismatch based design to tune the signaling magnitude and sensitivity : https://doi.org/10.1002/anse.202500077

• Circular permutation : https://pubs.acs.org/doi/10.1021/jacsau.3c00781, https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000729/v1, https://pmc.ncbi.nlm.nih.gov/articles/PMC3866043/

• Spilitting aptamer (not really generalizable to many aptamers and splitting ability is structure-dependent) : https://pubs.rsc.org/en/content/articlelanding/2025/an/d4an01226g

Biophysics-guided aptamer translation

Redox-modified aptamers are expensive so it would be practical to perform the translation step using the label-free aptamers. It is demonstrated that the change in binding enthalpy could be a good predictor for the functional electrochemical sensors. Therefore, enthalpy-guided sequence optimization could be conducted using ITC. 

• Biophysics-guided aptamer re-engineering : https://doi.org/10.1002/anse.202500077, https://doi.org/10.1021/acs.bioconjchem.2c00275 

• The positioning of the redox reporter significantly influences sensor performance, and structure-informed sequence redesign can help generate functional sensors : https : //www.biorxiv.org/content/10.1101/2025.11.27.690961v1.full.pdf, https://www.nature.com/articles/s41565-023-01591-0, https://www.sciencedirect.com/science/article/abs/pii/S0003267020311223

• E-AB sensor fabrication protocol : https://www.nature.com/articles/nprot.2007.413

• Electrochemical techniques used for sensor interrogation : https://doi.org/10.1039/D3SD00083D, https://doi.org/10.1021/acselectrochem.5c00316

• Folding-based electrochemical biosensors: The case for responsive nucleic acid architectures : https://pubs.acs.org/doi/10.1021/ar900165x

• ***EAB sensors with tunable detection range (review) : https://pubs.acs.org/doi/10.1021/acs.analchem.2c04498

• To some extent, increasing aptamer density can enhance the signal, but this effect is not universally generalizable across all aptamer sequences. As such, optimization is necessary to identify the optimal packing density for each aptamer.

• Increased amplitude in SWV can increase signal : https://pubs.acs.org/doi/10.1021/acs.analchem.6b03227

• Target-assisted immobilization : https://pubs.acs.org/doi/10.1021/acsami.0c20707. Of note, the target concentration and the ionic strength of the binding buffer during sensor fabrication should be tailored to each aptamer.

• Co-deposition of aptamer and alkanthiol layer : https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.4c00585

• Different monolayers (e.g., carboxylate terminated) : https://pubs.acs.org/doi/10.1021/acsami.4c21790

• Ferricyanide-mediated supports ultrasensitive analysis of cardiac troponin I in clinical samples : https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.4c01979

• Nanoconfined constructs for EAB sensors : https://doi.org/10.1016/j.coelec.2025.101695 

• Can calibration-free sensors be realized? https://doi.org/10.1021/acssensors.6b00247

• Calibration-free measurements : https://pubs.acs.org/doi/10.1021/jacs.7b05412

• Kinetic differential measuremens (KDM) : https://pmc.ncbi.nlm.nih.gov/articles/PMC8976050/

• Calibration-free FT-EIS : https://pubs.acs.org/doi/10.1021/acssensors.3c00632

• Dual-frequency and ratiometric approaches (rKDM) : https://pubs.acs.org/doi/10.1021/acssensors.4c00516

• Corection of pH-induced signal variations  : https://pubs.acs.org/doi/10.1021/acssensors.6c00737

Sensor degradation studies

• Signal drift mechanism and wave-form effects on signal degradation : https://pubs.acs.org/doi/10.1021/acssensors.1c01183

• Blood component effects : https://pubs.acs.org/doi/10.1021/acssensors.5c01267

• Signaling decay in SWV : https://pubs.acs.org/doi/10.1021/acs.analchem.2c05158

• Nuclease hydrolysis effects : https://pubs.acs.org/doi/10.1021/acs.langmuir.1c03236

New monolayers

• Lubricin (proteoglycan 4; PRG4)-derived glycocalyx layer : https://pubs.acs.org/doi/10.1021/acssensors.6c00192

• Zwitterionic membranes and zwitterion-based blocking layers with antifouling properties :  https://doi.org/10.1021/acssensors.2c02403, https://pubs.acs.org/doi/abs/10.1021/acsapm.5c02297

• Biomimetic phosphatidylcholine-terminated monolayer: https://onlinelibrary.wiley.com/doi/10.1002/anie.201700748

• Surface charge effects of monovalent and zwitterionic monolayers to differentiate structurally similar aminoglycosides : https://doi.org/10.1016/j.bios.2025.117229

• Tetra-polyethylene glycol : https://doi.org/10.1021/acsami.5c25540 

• Au–C≡C anchoring group : https://doi.org/10.1039/D6SC02701F

Aptamer enantiomeric inversion

• Mirror-image L-DNA aptamers: https://pubs.acs.org/doi/10.1021/jacs.5c22265

• Xenonucleic acid-based aptamer (maybe abolish initial aptamer functionality as every small modification in the aptamer structure could kill its function): https://pubs.acs.org/doi/10.1021/jacs.5c22605

Other strategies

• Implantable hydrogel-protective: https://pubs.acs.org/doi/10.1021/acsnano.3c06520

• Serum proteins-coagulated using thrombin followed by filtration to remove the coagulated material: https://www.nature.com/articles/s44328-025-00066-7

• Nafion coated nanopore electrode : https://doi.org/10.1039/D4FD00144C

Proteins

• C-reactive protein : https://doi.org/10.1021/acsabm.4c00061; streptavidin-driven artifacts for CRP : https://doi.org/10.26434/chemrxiv.15001875/v1 

• Platelet-derived growth factor : https://pubs.acs.org/doi/10.1021/ac061592s

• Thrombin : https://pubs.acs.org/doi/10.1021/la800801v, https://pubs.acs.org/doi/10.1021/ar900165x

Small molecules (followed by alphabetical order)

• Aminoglycosides (Kanamycin) : https://pubs.acs.org/doi/10.1021/jacs.5c22605, new Kanamycin A aptamer https://doi.org/10.1021/acs.biochem.5c00778, new Tobramycin aptamer https://doi.org/10.1016/j.bios.2026.118569 

• Adenosine/ATP/ADP/AMP : https://pubs.rsc.org/en/content/articlelanding/2010/an/b921253a, https://pubs.acs.org/doi/10.1021/acssensors.3c01624, https://pubs.acs.org/doi/10.1021/acsami.0c20707, https://pubs.acs.org/doi/10.1021/acselectrochem.5c00341, new ATP aptamer https://onlinelibrary.wiley.com/doi/10.1002/smll.202508898

• Cocaine : Old TWJ cocaine/quinine aptamer https://pubs.acs.org/doi/10.1021/ja806531z, new cocaine selective aptamer https://pubs.acs.org/doi/10.1021/jacs.3c11350, four generations of cocaine aptamer https://doi.org/10.1021/jacsau.3c00781 

• Cortisol : https://doi.org/10.1021/acssensors.2c02403, https://doi.org/10.1016/j.snb.2025.138284

• Dopamine : DA-3bp https://pubs.acs.org/doi/10.1021/acselectrochem.5c00341, DA-Mut3-Del6 https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cbic.202400493, RKEC1 MB internal construct https://www.biorxiv.org/content/10.1101/2025.11.27.690961v1, new Dopamine aptamer (mutant) https://doi.org/10.1039/D5SC09660J 

• Doxurorubicin : https://pubs.rsc.org/en/content/articlelanding/2021/cc/d1cc04557a

• Emtricitabine :  https://doi.org/10.1002/adsr.202400191 

• Fentanyl : https://doi.org/10.1021/acs.analchem.3c04104

• Glucose : https://pubs.acs.org/doi/10.1021/acssensors.3c01624, https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/adma.202313743

• Irinotecan : https://pubs.rsc.org/en/content/articlelanding/2019/sc/c9sc01495k, https://doi.org/10.1021/acs.analchem.2c00829

• L-Phenyalanine : https://pubs.acs.org/doi/full/10.1021/acs.analchem.0c05024

• L-Tryptophan : https://link.springer.com/article/10.1007/s00216-019-01645-0, https://pubs.acs.org/doi/10.1021/acsnano.4c06813

• L-/D-Lactate : https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/adma.202313743, new Lactate aptamer https://doi.org/10.1021/acs.analchem.5c07149 

• Methotrexate : MTX1-stem 4 https://pubs.acs.org/doi/10.1021/acssensors.2c01894, HMX24 https://doi.org/10.1016/j.bios.2024.116680, https://doi.org/10.1021/acsptsci.6c00142 

• Ochratoxin A : https://pubs.acs.org/doi/10.1021/acs.analchem.2c03566

• Serotonin : https://pubs.acs.org/doi/10.1021/acs.langmuir.5c01725, https://pubs.acs.org/doi/full/10.1021/acs.analchem.2c05335

• Theophylline : https://iopscience.iop.org/article/10.1149/2754-2726/ad71de

• Uric acid : https://pubs.acs.org/doi/10.1021/acs.analchem.5c01312

• Vancomycin : van-45 https://pubs.acs.org/doi/10.1021/acssensors.9b01616, van-28 https://pubs.acs.org/doi/full/10.1021/acsami.4c21790, clinical pilot study https://www.nature.com/articles/s41587-026-03010-w, plasma-to-interstitial-fluid study https://www.mdpi.com/1424-8220/26/7/2233 

Multiplexed sensing

• Cocaine and dopamine : https://doi.org/10.1039/D4CC01452A

• Methotrexate and its metabolite DAMPA : https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000729/v1

• Smart closed-loop systems in personalized healthcare: advances and outlook (long review) : https://doi.org/10.1002/admt.202502260

• Conformational-switch biosensors as novel tools to support continuous, real-time molecular monitoring in lab-on-a-chip devices (review) : https://doi.org/10.1039/D2LC00716A

• Goal of closed-loop systems and their requirements : https://blog.johner-institute.com/regulatory-affairs/closed-loop-systems/

• Closed-loop system for control of medically induced coma and other states of anesthesia : https://iopscience.iop.org/article/10.1088/1741-2560/13/6/066019

• ***Closed-loop administration of general anaesthesia: from sensor to medical device :  https://doi.org/10.1515/pthp-2017-0017

• PID system for adjusting vancomycin dosing: https://pubs.acs.org/doi/10.1021/acssensors.9b01616

• Closed-loop system for continuous infusion of muscle relaxants : https://doi.org/10.1016/S0025-6196(12)60901-X

• Simple minimally-invasive automatic antidote delivery device A2D2 towards closed-loop reversal of opioid overdose : https://doi.org/10.1016/j.jconrel.2019.05.04

• Electrochemical pump for remotely controlled, on-demand drug delivery : https://doi.org/10.1039/D5LC00708A

• ***Cross-reactive chemical sensor arrays: https://pubs.acs.org/doi/10.1021/cr980102w

• ***Generation of species cross-reactive aptamers using “Toggle” SELEX : https://doi.org/10.1006/mthe.2001.0495 

• ***Cross-reactive/Class-specific aptamer selection (Toggle SELEX): https://www.sciencedirect.com/science/article/pii/S1525001601904952, https://academic.oup.com/nar/article/47/12/e71/5423605

• Cross-reactive TWJ aptamer array: https://pubs.acs.org/doi/10.1021/ja2084256

• Cross-reactive aptamers for the detection of 24 quinolones : https://doi.org/10.1021/acs.analchem.4c00616

• Discrimination of structurally similar adenosine phosphates : https://doi.org/10.1016/j.talanta.2026.129808

• Rational selection of minimal sensor arrays : https://doi.org/10.1021/acs.analchem.5c07372 

• Sensor array for accurate discrimination and quantification of tetracyclines : https://pubs.acs.org/doi/10.1021/acs.analchem.6c01082  

• Current platforms and emerging methods : https://pubs.acs.org/doi/10.1021/acs.analchem.5c02331

• A review of CYP-mediated drug Interactions: mechanisms and in vitro drug-drug interaction assessment : https://doi.org/10.3390/biom14010099

• Aptamer-enabled probing nanoscale biological membranes (i.e., aptamer selection, assay development, clinical analysis, biomarker discovery) : https://doi.org/10.1021/acs.nanolett.6c00387

• Multi-well aptasensor platform : https://www.science.org/doi/10.1126/sciadv.adn5875

• High-throughput phenotypic screen to identify FoxP3 regulators in primary T cells : https://doi.org/10.1021/acschembio.5c01019 

• An aminoglycoside microarray platform : https://doi.org/10.1021/bi701071h 

• Electrochemical Methods : Fundamentals and Applications, Allen J. Bard, Larry R. Faulkner, Henry S. White.

• Algorithm-powered analyzer for continuous electrochemistry (A-PACE) : https://doi.org/10.1101/2025.09.28.678418

• Software for the analysis and continuous monitoring of electrochemical systems (SACMES) : https://doi.org/10.1021/acs.analchem.9b02553

• Daniel Carroll's electrochemical blog : https://danielpatrickcarroll.substack.com/p/electrochemical-insights-weekly-2d3

Chemometrics for Pattern Recognition, Richard G. Brereton.

Multivariate chemical analysis: From sensors to sensor arrays: https://www.sciencedirect.com/science/article/abs/pii/S100184172300918X

Groups working on cross-reactive arrays: 

• Eric Asylin (U. Texas at Austin) https://anslyn.cm.utexas.edu/AnslynWebsite/EricVAnslyn.html

• Vincent Rotello (U. Massachusetts at Amherst) https://elements.chem.umass.edu/rotellogroup/

• https://plaxco.chem.ucsb.edu/

• https://chemistry.sciences.ncsu.edu/2023/04/25/chemist-xiao-develops-high-performance-bio-receptors-aptamers-and-innovative-biosensors/

• https://netzlab.unc.edu/

• https://www.chem.fsu.edu/~lazenby/

• https://ebiosensors.recherche.usherbrooke.ca/

• https://geneticsensing.com/

• https://uwaterloo.ca/electrical-computer-engineering/profile/m2poudin

• https://stc.uniroma2.it/?page_id=8101&cn-entry-slug=andrea-idili&lang=en

Other blogs

• https://davidwallauch.wordpress.com/

• https://proseandpassion.blogspot.com/p/michael-gross-science-writer.html

• https://chemtips.wordpress.com/

• https://chemjobber.blogspot.com/2026/04/the-2026-chemistry-faculty-jobs-list.html

• https://www.yorku.ca/skrylov/teaching.html

Research/teaching statement example

• https://sites.google.com/site/aseemk/home

CNRS application tips

• https://dominik-peters.de/blog/apply-to-cnrs/

• https://blitiri.blogspot.com/2013/01/cnrs-positions-tips-for-foreign.html

• https://games-automata-play.github.io/blog/applying_cnrs/

• https://mathurinm.github.io/cnrs_inria_advice/