Technical Resources - iGii

Understanding sensitivity in biosensors - metrics, surface area and detection principles

Written by iGii | Sep 18, 2025 10:29:37 AM

Sensitivity determines how effectively a biosensor can detect and quantify low concentrations of a target analyte like proteins, metabolites or nucleic acids in complex biological matrices. In electrochemical biosensing, quantifying sensitivity requires a nuanced understanding of signal amplification, background noise, surface chemistry and transduction physics. 

When it comes to calculating precise sensitivity in biosensors, engineers need an understanding of how to leverage electrochemical detection methods. These include key metrics such as including signal-to-noise ratio (SNR), limit of detection (LOD) and response slope. On top of that, they need knowledge surrounding calibration curves and electrochemical impedance spectroscopy (EIS) or voltammetry.

Key sensitivity metrics in biosensing

Signal to noise ratio (SNR) 

The signal-to-noise ratio (SNR) reflects how clearly a biosensor can detect the presence of an analyte against the background "noise" of the system. An SNR ≥ 3 is generally accepted as the threshold for detection. Higher SNRs indicate more reliable and precise detection as the signal produced by the target is strong and distinct, which is essential for reliable detection. This is especially the case at low concentrations where differences are subtle. The equation is as follows: 

SNR=Signal/Noise

 

  • Signal: This is the output from the biosensor when it detects the target analyte. In electrochemical biosensors, the signal might be a change in current, voltage, or resistance.
  • Noise: This refers to random fluctuations or background interference in the sensor output that are not related to the analyte. Noise can come from electrical components, the sample matrix, temperature, or even human handling.

Response slope (sensitivity)

The response slope of a biosensor represents how much the signal changes in response to a change in analyte concentration. It’s a measure of how “sensitive” the device is and how sharply and predictably it responds as analyte levels vary. This is important for quantifying results accurately and distinguishing between similar concentrations. The general formula is:

Sensitivity=Change in Signal/Change in Concentration

Sensitivity calculation is essential to determine how precise your sensor is across a range of concentrations. A flat slope may indicate weak binding or poor electron transfer, even if the sensor gives a detectable signal. 

Limit of detection (LOD) 

The limit of detection (LOD) defines the lowest concentration of an analyte that the biosensor can detect with reasonable certainty. It’s an important benchmark in biosensing, particularly for clinical diagnostics or environmental monitoring where early or trace-level detection can make the difference between success and failure.

LOD=3 x Baseline Noise/Sensitivity

The LOD tells you the lowest concentration of analyte that your sensor can reliably detect. The “3×” in the formula is a statistical threshold, meaning the signal must be at least three times greater than the noise to be considered real. For cytokines like IL-10 or biomarkers like cortisol, concentrations can be in the fg/mL to pg/mL range, and your sensor’s LOD must be 
lower than that to be useful.

Electroactive surface area (ESA)

The electroactive surface area (ESA) of the transducer material refers to the actual interface available for electron transfer, which can be significantly larger due to microstructuring or porosity. A larger ESA enables higher loading of biorecognition elements such as antibodies, enzymes or aptamers. This increases the likelihood of analyte interaction at the electrode surface, which in turn amplifies the electrochemical response. This leads to:

 

  • SNR increases, as more signal is generated per analyte interaction
  • The response slope becoming steeper, indicating greater sensitivity
  • LOD decreases, as even small concentrations generate detectable signals

To be able to provide meaningful comparisons of sensitivity across sensors it is important to normalise the electroactive surface area. In order to estimate the electroactive surface area (ESA) of a biosensor electrode, cyclic voltammetry (CV) is a widely used technique. Cyclic voltammetry estimates electroactive surface area by relating the peak current from a redox reaction to the area available for electron transfer. This is especially important for high-surface-area materials like novel carbon-based transducers where the true reactive area far exceeds the flat geometric footprint. 

Putting it all together with calibration curves

To calculate SNR, LOD, and sensitivity, you first need to collect data by running your sensor across a range of known concentrations. A calibration curve plots the sensor’s signal (e.g., current, voltage, resistance) against these known analyte concentrations. This curve must be linear (or show a predictable non-linear response such as Langmuir-type binding) across the relevant analytical range. Without it, your biosensor might show a current, voltage, or impedance change but you’d have no way of knowing what concentration that signal corresponds to.

Steps to build a calibration curve

  1. Run measurements at various analyte concentrations (e.g. 1 pg/mL to 1 ng/mL).
  2. Record the signal at each point (e.g. current, voltage, or resistance).
  3. Plot signal vs. concentration to get your calibration curve. (If the signal is current or charge-based, and the electrodes differ in structure or material, normalising to electroactive surface area can improve the comparability of sensitivity values.)
  4. Fit a straight line (or binding curve) through the data:
    The slope = sensitivity
    The scatter at zero concentration = noise (used for LOD and SNR)

Enhance your biosensor sensitivity with a scalable transducer material

High sensitivity is fundamentally shaped by the transducer material. Without a scalable, reproducible surface, even the best signal metrics mean little at commercial scale.

Gii changes that. With its high electroactive surface area, low noise and consistent manufacturing, Gii enables reliable detection at femtogram levels without compromising on scalability or sustainability.

If sensitivity is critical to your biosensor’s success, Gii makes it measurable, manufacturable and market-ready. Download the guide to see how Gii can elevate your platform through features like multi-analyte capabilites.