Mathematical modeling of bioassays

Sotnikov, Dmitriy V.; Zherdev, Anatoly V.; Dzantiev, Boris B.

doi:10.1134/s0006297917130119

Cited by 15 publications

(11 citation statements)

References 182 publications

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“…An important feature of LFIAs is their dynamic range for analyte quantification. Several LFIA design modifications have previously been proposed for expanding the dynamic range (11,(16)(17)(18)(19). However, even a slight design modification causes a long-time delay in testing and manufacturing.…”

Section: Discussionmentioning

confidence: 99%

“…Although an elegant demonstration, the fundamental transport-reaction phenomena that govern the real time progression of the T/C ratio and how this time progression relates to antigen concentration is not understood. In fact, although several transport-reaction models of LFIAs have been developed (11,(16)(17)(18)(19), all these models only concern the development of signal at the test line; transport phenomena at the control line of an LFIA have not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Transport Phenomena at Test and Control Lines in Lateral Flow Immunoassays Reveal a Path to Expanding Their Dynamic Range

Sathishkumar¹,

Toley²

2020

Preprint

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<p>This study presents theoretical underpinnings for how the dynamic range of a lateral flow immunoassay (LFIA) may be expanded by real-time imaging. The dynamic range of a sandwich LFIA is limited by the ‘hook effect’, according to which, test line signal intensities reduce with increasing analyte concentration beyond a threshold analyte concentration. Rey et al. (<i>Anal Chem</i>, 2017, 89(9)) have shown experimentally that the hook effect in sandwich LFIAs may be mitigated by real-time imaging of test and control line, but theoretical understanding of the transport phenomena that govern this phenomenon is lacking. In fact, transport phenomena at the control line of an LFIA have never been modelled. In this paper, we use a transport-reaction model to understand how the kinetics of signal generation at the test and control lines of an LFIA relate to analyte concentration. Using this model, we developed a method for determination of analyte concentration accurately over a much larger range than the traditional end-point detection method. The model was validated using a commercially available lateral flow assay (home pregnancy test) on which real time imaging was conducted using a time-lapse app on a smartphone; there was a strong agreement between the predictions of our model and experiments results. The newly developed readout method increased the dynamic range for the detection of human chorionic gonadotropin (hCG) to 3 orders of magnitude (compared to ~1.5 orders of magnitude achieved by traditional end-point detection), without any modification to the test strip.</p>

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transport Phenomena at Test and Control Lines in Lateral Flow Immunoassays Reveal a Path to Expanding Their Dynamic Range

Sathishkumar¹,

Toley²

2020

Preprint

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“…In other words, the binding of antibodies to the analyte-protein conjugate should be somewhat worse than with the native analyte. The influence of the characteristics of immunoreagents on the sensitivity of analysis is considered in detail in works devoted to the mathematical modeling of LFIA [25][26][27][28][29][30].…”

Section: Proper Receptor For Lfiamentioning

confidence: 99%

Ways to Reach Lower Detection Limits of Lateral Flow Immunoassays

Zherdev¹,

Dzantiev²

2018

Rapid Test - Advances in Design, Format and Diagnostic Applications

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This chapter considers factors influencing sensitivity of lateral flow immunoassay and modern developments that are focused on reaching lower detection limits. The existing variety of proposed approaches is classified in accordance with the "big five rules" for these assays, including proper sample, receptor, interaction, response, and output. The solutions for rapid extraction of target analytes and preventing negative influence of extractants are considered. Role to antibodies affinity and specificity is characterized. Potential of alternate bioreceptor molecules is discussed. Immunoreactants' compositions, concentrations, and locations on the test strip are characterized as factors determining assay parameters. The existing variety of labels is compared in terms of their optical and alternate registration. Tools to modulate a sequence of analytical reactions and to form aggregates of the detected labels are considered. The discussed approaches are illustrated through developments of test strips for detection of mycotoxins, veterinary drugs, and other analytes.The overall design of the immunochromatographic test strip is shown in Figure 1. It is a composite of several membranes of different structures and porosities, fixed on a support. The bundling of the test strip can vary, so it makes sense to consider its design based on what analytical tasks are being performed on its different sites.A. Typically, the lower portion of the test strip contains a sample pad. It ensures the absorption of sample components, in which the presence of the target analyte is checked.B. The following is a section with immunoreagents that are washed out during the analysis and move upward along with the components of the sample. As a rule, a conjugate pad forms this zone. It contains a conjugate of antibodies against the target analyte with a nanodispersed label-particles of colored latex, colloidal gold, and so on.The next two sections are located on the main working membrane of the test strip. C.First, there is a zone along which the movement of the absorbed components of the sample and the washed immunoreagents continues. During this movement, immune reactions occur, and specific intermolecular complexes are formed. D.Next, a mixture of reacted and unreacted molecules enters the binding area with immobilized immunoreagents. Depending on whether the target analyte was present in the sample and in what amount, binding of labeled immune complexes occurs in certain areas (in the traditional case, with the formation of narrow colored lines). Usually, additional reagents are located here to control the functionality of the test system. E. The upper part of the test strip with the final pad, usually structurally similar to the sample pad, ensures the further movement of the reaction mixture under the action of capillary forces and the washing of unreacted components from the underlying areas. These processes allow the label's binding to be evaluated correctly.Membrane components of the test strip are fixed on a plastic support and partia...

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“…In the present study, mathematical modeling of the expected effects of the approach described above and experimental verification were carried out for two immunoassay formats. The mathematical model uses previously proposed descriptions of competitive immunoassays [48][49][50] and focuses on unexplored regularities in antigens differing in affinity without consideration of non-target interferences [51]. The obtained theoretical solutions show the versatility of the idea and the promise of its application for different compounds.…”

Section: Introductionmentioning

confidence: 99%

Changing Cross-Reactivity for Different Immunoassays Using the Same Antibodies: Theoretical Description and Experimental Confirmation

et al. 2021

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Many applications of immunoassays involve the possible presence of structurally similar compounds that bind with antibodies, but with different affinities. In this regard, an important characteristic of an immunoassay is its cross-reactivity: the possibility of detecting various compounds in comparison with a certain standard. Based on cross-reactivity, analytical systems are assessed as either high-selective (responding strictly to a specific compound) or low-selective (responding to a number of similar compounds). The present study demonstrates that cross-reactivity is not an intrinsic characteristic of antibodies but can vary for different formats of competitive immunoassays using the same antibodies. Assays with sensitive detection of markers and, accordingly, implementation at low concentrations of antibodies and modified (competing) antigens are characterized by lower cross-reactivities and are, thus, more specific than assays requiring high concentrations of markers and interacting reagents. This effect was confirmed by both mathematical modeling and experimental comparison of an enzyme immunoassay and a fluorescence polarization immunoassay of sulfonamides and fluoroquinolones. Thus, shifting to lower concentrations of reagents decreases cross-reactivities by up to five-fold. Moreover, the cross-reactivities are changed even in the same assay format by varying the ratio of immunoreactants’ concentrations and shifting from the kinetic or equilibrium mode of the antigen-antibody reaction. The described patterns demonstrate the possibility of modulating immunodetection selectivity without searching for new binding reactants.

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Mathematical modeling of bioassays

Cited by 15 publications

References 182 publications

Transport Phenomena at Test and Control Lines in Lateral Flow Immunoassays Reveal a Path to Expanding Their Dynamic Range

Transport Phenomena at Test and Control Lines in Lateral Flow Immunoassays Reveal a Path to Expanding Their Dynamic Range

Ways to Reach Lower Detection Limits of Lateral Flow Immunoassays

Changing Cross-Reactivity for Different Immunoassays Using the Same Antibodies: Theoretical Description and Experimental Confirmation

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