Upconverting nanophosphors as reporters in a highly sensitive heterogeneous immunoassay for cardiac troponin I

Sirkka, Nina; Lyytikäinen, Annika; Savukoski, Tanja; Soukka, Tero

doi:10.1016/j.aca.2016.04.027

Cited by 46 publications

(35 citation statements)

References 29 publications

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“…After the synthesis, the oleic acid‐covered UCNPs are insoluble in water and do not have any functional groups. Therefore, after removing the oleic acid the NaYF 4 :Yb 3+ ,Er 3+ and NaYF 4 :Yb 3+ ,Tm 3+ UCNPs were coated with PAA . After the PAA coating, the green‐emitting NaYF 4 :Yb 3+ ,Er 3+ UCNPs were conjugated to Mab‐5409 antibody and the blue‐emitting NaYF 4 :Yb 3+ ,Tm 3+ UCNPs to Mab‐5404.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, after removing the oleic acid the NaYF 4 :Yb 3 + ,Er 3 + and NaYF 4 :Yb 3 + ,Tm 3 + UCNPs were coated with PAA. [16] After the PAAc oating, the green-emitting NaYF 4 :Yb 3 + ,Er 3 + UCNPs were conjugated to Mab-5409 antibody and the blue-emitting NaYF 4 :Yb 3 + ,Tm 3 + UCNPs to Mab-5404. The Mab 5404 and Mab 5409 recognize two different epitopes on human TSH and therefore, enable simultaneous binding of green and blue emitting UCNPs to the same TSH molecule.…”

Section: Methodsmentioning

confidence: 99%

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Upconversion Cross‐Correlation Spectroscopy of a Sandwich Immunoassay

Lahtinen

Krause

Arppe

et al. 2018

Chemistry A European J

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Fluorescence correlation and cross‐correlation spectroscopy (FCS/FCCS) have enabled biologists to study processes of transport, binding, and enzymatic reactions in living cells. However, applying FCS and FCCS to samples such as whole blood and plasma is complicated as the fluorescence bursts of diffusing labels can be swamped by strong autofluorescence. Here we present cross‐correlation spectroscopy based on two upconversion nanoparticles emitting at different wavelengths on the anti‐Stokes side of a single excitation laser. This upconversion cross‐correlation spectroscopy (UCCS) approach allows us to completely remove all Stokes shifted autofluorescence background in biological material such as plasma. As a proof of concept, we evaluate the applicability of UCCS to a homogeneous sandwich immunoassay for thyroid stimulating hormone measured in buffer solution and in plasma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Upconversion Cross‐Correlation Spectroscopy of a Sandwich Immunoassay

Lahtinen

Krause

Arppe

et al. 2018

Chemistry A European J

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“…The use of recombinant Abs in recent cTnI assays is not yet widely reported, with the majority of immunoassays employing the use of monoclonal Abs. However, one group have opted to use recombinant Abs for cTnI detection in a luminescence-based immunoassay, citing the reduction in non-specific signals from the sample matrix due to the absence of the Fc region as an influencing factor [50]. This assay can detect cTnI at ng/L concentrations directly in plasma, a feature that substantially increases its compatibility towards POC integration.…”

Section: Biomarker Recognitionmentioning

confidence: 99%

Point-of-Care Compatibility of Ultra-Sensitive Detection Techniques for the Cardiac Biomarker Troponin I—Challenges and Potential Value

2018

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Cardiac biomarkers are frequently measured to provide guidance on the well-being of a patient in relation to cardiac health with many assays having been developed and widely utilised in clinical assessment. Effectively treating and managing cardiovascular disease (CVD) relies on swiftly responding to signs of cardiac symptoms, thus providing a basis for enhanced patient management and an overall better health outcome. Ultra-sensitive cardiac biomarker detection techniques play a pivotal role in improving the diagnostic capacity of an assay and thus enabling a better-informed decision. However, currently, the typical approach taken within healthcare depends on centralised laboratories performing analysis of cardiac biomarkers, thus restricting the roll-out of rapid diagnostics. Point-of-care testing (POCT) involves conducting the diagnostic test in the presence of the patient, with a short turnaround time, requiring small sample volumes without compromising the sensitivity of the assay. This technology is ideal for combatting CVD, thus the formulation of ultra-sensitive assays and the design of biosensors will be critically evaluated, focusing on the feasibility of these techniques for point-of-care (POC) integration. Moreover, there are several key factors, which in combination, contribute to the development of ultra-sensitive techniques, namely the incorporation of nanomaterials for sensitivity enhancement and manipulation of labelling methods. This review will explore the latest developments in cardiac biomarker detection, primarily focusing on the detection of cardiac troponin I (cTnI). Highly sensitive detection of cTnI is of paramount importance regarding the rapid rule-in/rule-out of acute myocardial infarction (AMI). Thus the challenges encountered during cTnI measurements are outlined in detail to assist in demonstrating the drawbacks of current commercial assays and the obstructions to standardisation. Furthermore, the added benefits of introducing multi-biomarker panels are reviewed, several key biomarkers are evaluated and the analytical benefits provided by multimarkers-based methods are highlighted.

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“…In the practice of an ultra-sensitive assay, the signal from a target analyte on the left side of detection window will be very small. Therefore, the minimization and suppression of the background signal that interferes with the valid target-derived signal should be accomplished simultaneously [ 21 , 22 ]. With this in mind, the use of conventional fluorophores in an immuno-analysis that requires high sensitivity, such as the detection of cardiac troponin I (cTnI) for AMI diagnosis, is not sufficient [ 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although the intensity of auto-fluorescence is usually weak, it represents a significant background signal that cannot be ignored, especially for an ultra-sensitive immunoassay. To find a strategy that enables the elimination of the adverse effect of auto-fluorescence, researchers have focused on the short lifetime of auto-fluorescence [ 22 , 24 ]. Because auto-fluorescence generates and then disappears quickly, the use of a novel fluorophore that exhibits a longer lifetime is a promising solution to this issue.…”

Section: Introductionmentioning

confidence: 99%

Encapsulation-Stabilized, Europium Containing Nanoparticle as a Probe for Time-Resolved luminescence Detection of Cardiac Troponin I

et al. 2017

Biosensors

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The use of a robust optical signaling probe with a high signal-to-noise ratio is important in the development of immunoassays. Lanthanide chelates are a promising material for this purpose, which provide time-resolved luminescence (TRL) due to their large Stokes shift and long luminescence lifetime. From this, they have attracted considerable interest in the in vitro diagnostics field. However, the direct use of lanthanide chelates is limited because their luminescent signal can be easily affected by various quenchers. To overcome this drawback, strategies that rely on the entrapment of lanthanide chelates inside nanoparticles, thereby enabling the protection of the lanthanide chelate from water, have been reported. However, the poor stability of the lanthanide-entrapped nanoparticles results in a significant fluctuation in TRL signal intensity, and this still remains a challenging issue. To address this, we have developed a Lanthanide chelate-Encapsulated Silica Nano Particle (LESNP) as a new immunosensing probe. In this approach, the lanthanide chelate is covalently crosslinked within the silane monomer during the silica nanoparticle formation. The resulting LESNP is physically stable and retains TRL properties of the parent lanthanide chelate. Using the probe, a highly sensitive, sandwich-based TRL immunoassay for the cardiac troponin I was conducted, exhibiting a limit of detection of 48 pg/mL. On the basis of the features of the LESNP such as TRL signaling capability, stability, and the ease of biofunctionalization, we expect that the LESNP can be widely applied in the development of TRL-based immunosensing.

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Upconverting nanophosphors as reporters in a highly sensitive heterogeneous immunoassay for cardiac troponin I

Cited by 46 publications

References 29 publications

Upconversion Cross‐Correlation Spectroscopy of a Sandwich Immunoassay

Upconversion Cross‐Correlation Spectroscopy of a Sandwich Immunoassay

Point-of-Care Compatibility of Ultra-Sensitive Detection Techniques for the Cardiac Biomarker Troponin I—Challenges and Potential Value

Encapsulation-Stabilized, Europium Containing Nanoparticle as a Probe for Time-Resolved luminescence Detection of Cardiac Troponin I

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