AI Insight
Researchers developed a biosensor called CAFET (Charge-Amplified Field-Effect Transistor) that uses DNA aptamers and a strand-displacement mechanism to detect small-molecule biomarkers at very low concentrations. When a target molecule binds to the aptamer, a pre-hybridized displacement strand is released, generating a net charge change within the Debye length that is translated into a measurable electrical signal; this signal can be further amplified by attaching a charge label to the displacement strand. The sensor achieved picomolar detection limits for 3-hydroxykynurenine and progesterone in undiluted human plasma, performing four orders of magnitude below the aptamer's own dissociation constant.
Why it matters
Detecting low-abundance biomarkers directly in complex biological fluids like blood plasma is a persistent challenge in clinical diagnostics; a modular, highly sensitive aptamer-based sensor of this kind could enable earlier disease detection and monitoring for conditions where relevant biomarkers circulate at very low concentrations.
⚠️ Preprint – Noch nicht peer-reviewed
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Aptamers are attractive receptors for small-molecule biomarker detection in complex samples because of their high stability, affinity, and specificity, but aptamer-based sensors generally lack the sensitivity to detect low-abundance analytes. As a solution, we developed the charge-amplified FET (CAFET) aptamer biosensor, which is designed to amplify the net charge variation within the Debye length that occurs as a consequence of aptamer-target binding. Our sensor utilizes a strand-displacement aptamer switch, which releases an initially-hybridized displacement strand (DS) upon target binding and thus induces a measurable net charge variation within the Debye length that is amplified to a large FET current response as signal readout. This signal can be further enhanced by adding a charge label to the DS. As a consequence, our sensor can achieve far greater sensitivity than previously described aptamer-FET sensors, where the binding-induced local charge variation is modest. We demonstrate 3-hydroxykynurenine and progesterone detection with a picomolar limit of detection in undiluted human plasma–four orders of magnitude lower than the dissociation constant (KD) of the aptamer component. The CAFET sensor design is modular and should be adaptable for the detection of a wide range of clinically-informative low-abundance analytes in complex samples.