Point-of-care technologies for molecular diagnostics using a drop of blood

Song, Yujun; Yu, Haiyang; Liu, Xuewu; Zhang, Xiaojing; Ferrari, Mauro; Qin, Lidong

doi:10.1016/j.tibtech.2014.01.003

Cited by 200 publications

(146 citation statements)

References 74 publications

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“…The reporter signal is amplified, generating a readout that is proportional to the concentration of target as determined using a previously derived calibration function. When a reporter-linked affinity reagent binds nonspecifically to the substrate, however, it gives rise to false positives that are indistinguishable from true protein capture events (8,9). It is obvious that the use of a single reporter-conjugated affinity reagent would generally produce a greater frequency of false positives than an assay based on two affinity reagents (both labeled with reporters), as a positive report from the former assay cannot be as confidently associated with the binding to a target protein.…”

mentioning

confidence: 99%

Dual-reporter SERS-based biomolecular assay with reduced false-positive signals

Chuong

Pallaoro

Chaves

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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We present a sensitive and quantitative protein detection assay that can efficiently distinguish between specific and nonspecific target binding. Our technique combines dual affinity reagents with surfaceenhanced Raman spectroscopy (SERS) and chemometric analysis. We link one Raman reporter-tagged affinity reagent to gold nanoparticles and another to a gold film, such that protein-binding events create a "hot spot" with strong SERS spectra from both Raman reporter molecules. Any signal generated in this context is indicative of recognition by both affinity labels, whereas signals generated by nonspecific binding lack one or the other label, enabling us to efficiently distinguish true from false positives. We show that the number of hot spots per unit area of our substrate offers a quantitative measure of analyte concentration and demonstrate that this duallabel, SERS-linked aptasensor assay can sensitively and selectively detect human α-thrombin in 1% human serum with a limit of detection of 86 pM.surface-enhanced Raman spectroscopy | SERS | protein detection | nanoparticle | ELISA

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mentioning

confidence: 99%

Dual-reporter SERS-based biomolecular assay with reduced false-positive signals

Chuong

Pallaoro

Chaves

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Fourth and most important, for prehospital biomarkers, new large stroke cohorts have recently been recruited for dedicated discovery of prehospital biomarkers, with first blood samples obtained on scene, within the golden hour after symptom onset [18,19]. Finally, ongoing progress in the development of POC technology has provided a wide range of novel measurement techniques for development of rapid ambulance assays [20].…”

Section: Future Progressmentioning

confidence: 99%

How Development of Blood Biomarkers Could Benefit Prehospital Management of Acute Stroke

2017

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Stroke is one of the leading causes of death worldwide and leaves most survivors with permanent disability [1,2]. Unfortunately, treatment options of acute stroke are still limited. In developed urban hospitals roughly a third of all ischemic stroke patients receive urgent recanalization therapy, in other words thrombolysis with recombinant tissue plasminogen activator (rtPA) and/or endovascular mechanical thrombectomy for large vessel occlusion (LVO). These treatments are highly efficacious and cost effective, but remain markedly underused [3]. Furthermore, their efficacy is time dependent, with strict therapeutic windows. To enhance the stroke chain of survival, current guidelines recommend a tiered system with acute stroke ready hospitals, primary stroke centers and comprehensive stroke centers to ensure timely initiation of intravenous rtPA with the least possible delay after symptom onset and rapid triage of large vessel occlusions eligible for thrombectomy in a comprehensive stroke center [3].The challenge of stroke diagnostics Time delay in the prehospital phase is the most important reason for missing recanalization therapy. Even for patients meeting the appropriate time window, the median prehospital delay is commonly around 2 h [4]. Emergency medical services (EMS) are challenged with the difficult task of identifying likely acute stroke from the wide range of acutely ill patients and ensuring rapid transport to the appropriate emergency department for immediate neurological examination and diagnostic brain imaging. For now, the main diagnostic groups causing acute strokelike symptoms, namely ischemic stroke, transient ischemic attack, hemorrhagic stroke and conditions mimicking stroke, can only be differentiated with hospital-based tests. EMS are therefore restricted to using simple, nonspecific clinical scales for stroke recognition, preventing them from initiating specific treatments.Mobile CT-equipped ambulances, directed by an onboard stroke neurologist or telemedicine consultation, are one active approach to front load diagnostic and therapeutic procedures and reduce treatment delays [5,6], but require significant resources and are only applicable in urban settings, missing rural areas with longer transportation distances. What is clearly missing is an easier surrogate marker for recognizing the condition of brain tissue (either biochemical or functional) while the described, tiered prehospital stroke management is being advanced. Such markers, including blood troponin measurement and ECG recording, are widely used in the prehospital management of acute myocardial infarction, but are still unavailable for stroke. Useful point-of-care (POC) blood tests would have the significant benefit of being relatively inexpensive and more easily applicable around the world.

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“…Key considerations in the choice of an appropriate technology are the ability to multiplex, assay time, cost, reliability and simplicity (Song et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Multiplexed, label-free detection of biomarkers using aptamers and Tunable Resistive Pulse Sensing (AptaTRPS)

Billinge

Platt

2015

Biosensors and Bioelectronics

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Citation: BILLINGE, E.R. and PLATT, M., 2015. Multiplexed, label-free detection of biomarkers using aptamers and Tunable Resistive Pulse Sensing (AptaTRPS). Biosensors and Bioelectronics, 68, Additional Information:• NOTICE: this is the author's version of a work that was accepted for publication in Biosensors and Bioelectronics.Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be re- we believe are integral to bead-based assays and demonstrate a general method for a multiplexed assay. In summary, we have explored the effects of beads size, concentration, potential bias, pH and aptamer affinity to enhance the sensitivity and practically of a TRPS aptasensor. The method utilises the fact the binding of the aptamer to the protein results in a change in charge density on the bead surface, the isoelectric point of the protein then dominates the mobility of the beads, creating a multiplexed assay termed AptaTRPS. By alteration of the applied potential to the instrument it is possible to produce a positive signal in a simple multiplexed assay.

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Point-of-care technologies for molecular diagnostics using a drop of blood

Cited by 200 publications

References 74 publications

Dual-reporter SERS-based biomolecular assay with reduced false-positive signals

Dual-reporter SERS-based biomolecular assay with reduced false-positive signals

How Development of Blood Biomarkers Could Benefit Prehospital Management of Acute Stroke

Multiplexed, label-free detection of biomarkers using aptamers and Tunable Resistive Pulse Sensing (AptaTRPS)

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