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Review
. 2018 Jun 26;18(7):2038.
doi: 10.3390/s18072038.

On the Determination of Uncertainty and Limit of Detection in Label-Free Biosensors

Álvaro Lavín  1   2 , Jesús de Vicente  2   3 , Miguel Holgado  4   5 , María F Laguna  6   7 , Rafael Casquel  8   9 , Beatriz Santamaría  10   11 , María Victoria Maigler  12   13 , Ana L Hernández  14 , Yolanda Ramírez  15   16
Affiliations
Review

On the Determination of Uncertainty and Limit of Detection in Label-Free Biosensors

Álvaro Lavín et al. Sensors (Basel). .

Abstract

A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. This article clarifies and establishes a simple procedure to determine the calibration function and the uncertainty of the concentration measured at any point of the measuring interval of a generic label-free biosensor. The value of the limit of detection arises naturally from this model as the limit at which uncertainty tends when the concentration tends to zero. The need to provide additional information, such as the measurement interval and its linearity, among others, on the analytical systems and biosensor in addition to the detection limit is pointed out. Finally, the model is applied to curves that are typically obtained in immunoassays and a discussion is made on the application validity of the model and its limitations.

Keywords: calculation of the limit of detection; label-free biosensing performance; limit of quantification; measurement uncertainty.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Calibration function.
Figure 2
Figure 2
Gaussian function.
Figure 3
Figure 3
(A) Critical value, Limit of Detection, false positives and false negatives for the general case; (B) Critical value, Limit of Detection, false positives and false negatives for the case α = β.
Figure 3
Figure 3
(A) Critical value, Limit of Detection, false positives and false negatives for the general case; (B) Critical value, Limit of Detection, false positives and false negatives for the case α = β.
Figure 4
Figure 4
Concentration C versus response y through the calibration function.
Figure 5
Figure 5
Theoretical sets of points representing an immunoassay and calibration function build for the first nine points.
Figure 6
Figure 6
Data, calibration line, uncertainty band, limits of detection and quantification and measuring intervals for the given example.
Figure 7
Figure 7
Data and calibration lines for different measuring intervals for the given example.
Figure 8
Figure 8
Data, calibration line N = 9 and parabolic fit and parabolic fit sensitivity.
Figure 9
Figure 9
Data, calibration curve for parabolic fit, uncertainty band, limits of detection and quantification and measuring intervals for the given example.
Figure 10
Figure 10
Data from Table 4 and calibration curve for parabolic fit.
Figure 11
Figure 11
Inverse calibration function and uncertainty bands.
See this image and copyright information in PMC

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