Cardiac troponin biosensors: where are we now?

Figures & data

Table 1 Summary of commercially available troponin detection technologies

Commercially available troponin assays	99th percentile cut-off (ng/mL)	Time	Cost (USD)	Volume
CTnT
Elecsys, third generation (Roche, Basel, Switzerland) cTnI	0.01	60 min	31,148	150 μL
i-STAT (Abbott Point of Care, Princeton, NJ, USA)	0.08	10 min	420	17 μL
ACS:180 (Bayer, Leverkusen, Germany)	0.07	24 h	1,200	10 mL
Dimension Vista (Siemens, Munich, Germany)	0.05	10 min	278,000	20 μL
Architect (Abbott, Princeton, NJ, USA)	0.04	10 min	19,000	62 μL

Abbreviations: CTnT, cardiac troponin T; cTnI, cardiac troponin I.

Figure 1 Overview of techniques used for cardiac troponin sensing.

Figure 2 Working mechanism of cardiac troponin biosensors.

Table 2 Summary of cardiac troponin sensors

Description	Technique	LOD	Advantages of technique	Reference
Three-electrode cell using a GCE coated with porous graphene oxide; human troponin I as working electrode	Electrochemical	0.07 ng/mL	Inexpensive, label free; uses graphene, which has good electrochemical behavior and large active surface area; good selectivity and high sensitivity	18
AuNPs are deposited on a GCE, peptide probe is added to electrode; EIS response should increase with increasing concentration of troponin I	Electrochemical	2.4 pg/mL	Using an AuNP-modified GCE reduces background EIS signal and enhances EIS response; simple, sensitive, fast	62
Uses MIP technology with a three- electrode system	Electrochemical	0.027 nM	Detection time of 5 min, can be used without much sample pretreatment, simple, low cost of preparation, label free	20
SPR film is gold film evaporated on a glass slide modified by hollow AuNPs and immobilized with antibodies that target troponin	SPR	1.25 ng/mL	Gold film amplifies SPR response; fast, accurate, and straightforward detection	63
Gold sensor chip and prism-based SPR biosensor; experiments using direct and sandwich assays	SPR	5 ng/mL for standard sandwich assay; 0.5 ng/ mL using AuNP detector antibodies	Using the regeneration method, the SPR sensor can be reused for multiple samples; rapid response, can provide real-time data	64
AuNPs are functionalized and used as label	Optical (chemiluminescence or electrochemiluminescence)	0.06 ng/mL	High sensitivity, low background, simple	65
AuNPs are applied to PDMS film then covered with antibody. After cTnI is captured, a silver solution is dropped on to the sensor. The silver solution undergoes reduction and causes color changes	Optical (colorimetric)	0.01 ng/mL	Practical and easy to operate and fabricate	65
Multianalyte detection of CRP and cTnI using microfluidic networks in human plasma	Optical (fluorescence)	30 ng/mL	Low analyte volume (1 pL), multianalyte detection for better screening of markers in multiple samples	66
Fluoro-microbead guiding chip-based sandwich immunoassay for detection of cTnI	Optical (fluorescence)	0.1 ng/mL	Chip supports four immunosensing regions which can test four different concentrations of cTnI simultaneously; ease of signal quantification	67
Multianalyte detection using chemiluminescent immunoassay; ultrasound waves are used to enhance immobilization of the capture probe	ELISA; chemiluminometric	4.3 × 10^4 ng/mL	Short incubation time, prototype for automated robotic measurement of cardiac biomarkers, disposable	68
Phage-displayed peptides for detection of cTnl. ELISA results indicate binding interaction between troponin antigen and phage-displayed peptide	ELISA	0.002 ng/mL	Novel phage display technology for monitoring of cardiac cells in a culture in addition to detection of cTnI	69
Chemiluminometric biosensor system coupled with cross-flow chromatography to enable binding of antigen-capture probe and signal generation	ELISA	0.01 ng/mL	Rapid (detection time 30 s), biotin-streptavidin complex- enhanced signal response, reduced antibody concentration needed for detection	34
Streptavidin-terminated SAM of carboxymethyldextran based on SPR for detection of cTnT with the help of immobilized monoclonal anti-troponin T antibodies	SPR	0.01 ng/mL	Fast, sensitive, and specific for troponin in human sera; label-free analysis	70
SPR sensor developed on a commercial surface plasmon resonance device. Troponin receptor molecules are covalently immobilized using a thiol linker using cysteamine molecules	SPR	0.05 ng/mL	Cost-effective, reusable sensor; SDS surfactant used for regeneration of immunosensor; no dilution of serum required	71
Troponin detection using an immobilized monoclonal antibody of cTnT on the surface of thin gold film	SPR	0.068 ng/mL	Monoclonal antibody created using a peptide epitope with a protein- based screening method; enhances sensitivity of sensor	72
Optomagnetic immunoassay using magnetic nanoparticles, which are magnetically actuated and detected optically. Multiplexed sensor for detection of multiple analytes	Optomagnetic	0.0117 ng/mL	Rapid, sensitive, low cost, disposable kit; one-step assays can be developed using this technology	73
Detection of cTnI using a combinatorial technique of optical and magnetic technology. Sandwich immunoassay using superparamagnetic nanoparticles coupled with optical detection of generated signal	Optomagnetic	0.03 ng/mL	Rapid, sensitive, and point of care	74
Simultaneous detection of CRP and cTnI using PDMS-AuNPs	Impedimetric	0.01 ng/mL	Low LOD, low sample volume (1 μL)	66
Screen-printed electrodes coupled with streptavidin polystyrene microspheres for detection of cTnT	Impedimetric	0.2 ng/mL	Ideal for miniaturized systems, disposable	75
Quantum dot-based technique which uses an LCW platform to capture fluorescence. Protein A is bound to the capture probe for enhanced sensitivity	FRET	55 nM	LCW platform decreases the stearic hindrance of immobilized capture sites; high efficiency	76
Homogeneous sandwich assay using quenching property of AuNPs. Simultaneous interaction of dye molecules and AuNPs enhances the signal of the immunoassay for detection of cTnT	FRET	0.7 ng/mL	High efficiency; overall enhanced signal	77
Polypyrrole-based potentiometric biosensor for broad-spectrum detection of various analytes including troponin I	Potentiometric	0.01 ng/mL	Rapid, ultrasensitive, reproducible, wide dynamic range	78
Multiplexed detection of cTnT and cTnI on a disposable and flexible impedimetric biosensor. ZnO nanostructures enhance the signal of the electrode	Impedimetric	1 pg/mL	Multiplexing, low LOD, signal well above noise threshold	17

Abbreviations: LOD, limit of detection; GCE, glassy carbon electrode; AuNP, gold nanoparticle; EIS, electrochemical impedance spectroscopy; MIP, molecularly imprinted polymer; SPR, surface plasmon resonance; PDMS, poly(dimethylsiloxane); CRP, C-reactive protein; cTnI, cardiac troponin I; ELISA, enzyme-linked immunosorbent assay; SAM, self-assembled monolayer; cTnT, cardiac troponin T; SDS, sodium dodecyl sulfate; LCW, liquid-core waveguide; FRET, fluorescence resonance energy transfer.