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Table 1 Comparative analysis of the Translocation/Dwell-Time (T/TD) approach and the Nanopore Transduction Detection (NTD) approach.

From: The NTD Nanoscope: potential applications and implementations

(1) Feature Space. The T/DT approach typically has a single feature, the dwell time. Sometimes a second feature, the fixed blockade level observed, is also considered, but usually not more features sought (or engineered) than that. The NTD approach has multiple features, e.g., blockade HMM parameters, etc., with number and type according to modulator design objectives.

(2) Versatility. T/DT: highly engineered/pre-processed for detection application to a particular target. NTD: requires minimal preparation/augmentation to the transduction platform via use of separately provided binding moieties (antibody or aptamer, for example) for particular target or biomarker (which are then simply linked to modulator)

(3) Speed. T/DT: Slow: entire detection “process” is at the channel, and typically restricted on processing speed to the average time-scale feature (dwell-time) for the longest-lived blockade signal class. NTD: Fast: feature extraction not dependent on dwell-time. Very low probability to get a false positive.

(4) Multichannel. T/DT: Method not amenable to multichannel gain with single-potential platform (can’t resolve single-channel blockade signal with multichannel noise). NTD: Have multichannel gain due to rich signal resolution capabilities of an engineered modulator molecule.

(5) Feature Refinement/Engineering. T/DT: No buffer modifications or off-channel detection extensions via introduction of substrates; the weak feature set limited to dwell-time doesn’t allow such methods to be utilized. NTD: Have “lock-and-key” level signal resolution. The introduction of off-channel substrates in the buffer solution can increase sensitivity.

(6) Multiplex capabilities. T/DT: Each modified channel is limited to detect a single analyte or single bond-change-event detection, so no multiplexing without brute force production of arrays of T/DT detectors in a semiconductor production setting. NTD: Supports multi-transducer, multi-analyte detection from a single sample. Supports multichannel with a single aperture.