Label-Free Impedance Biosensors: Opportunities and Challenges

Abstract

Impedance biosensors are a class of electrical biosensors that show promise for point-of-care and other applications due to low cost, ease of miniaturization, and label-free operation. Unlabeled DNA and protein targets can be detected by monitoring changes in surface impedance when a target molecule binds to an immobilized probe. The affinity capture step leads to challenges shared by all label-free affinity biosensors; these challenges are discussed along with others unique to impedance readout. Various possible mechanisms for impedance change upon target binding are discussed. We critically summarize accomplishments of past label-free impedance biosensors and identify areas for future research.

Fig. 1.

Generalized affinity biosensor, showing a) the signal flow, b) the physical arrangement, and c) the steps involved.

Fig. 2.

Generalized sandwich assay. The secondary antibody can provide increased selectivity and allows a well-known entity to be labeled instead of the (variable) target. However, a label-free scheme allows real-time detection and eliminates the time and cost of labeling.

Fig. 3.

Common circuit models for a) nonfaradaic and b) faradaic interfaces. See Section 4.6 for circuit elements.

Fig. 4.

Example nonfaradaic and faradaic impedance data in both Nyquist (a) and magnitude/phase (b) representations, along with dominating element. R_sol = 1 kΩ, C_surf = 10 nF with m = 0.9, R_leak = 500 kΩ R_ct = 100 kΩ, and Z_w coefficient 10⁻⁵.