Quantitative Lateral Flow Strip Sensor Using Highly Doped Upconversion Nanoparticles

Abstract

Paper-based lateral flow assays, though being lowcost and widely used for rapid in vitro diagnostics, are indicative and do not provide sufficient sensitivity for the detection and quantification of low abundant biomarkers for early stage cancer diagnosis. Here, we design a compact device to create a focused illumination spot with high irradiance, which activates a range of highly doped 50 nm upconversion nanoparticles (UCNPs) to produce orders of magnitude brighter emissions. The device employs a very low-cost laser diode, simplified excitation, and collection optics and permits a mobile phone camera to record the results. Using highly erbium ion (Er 3+ )-doped and thulium ion (Tm 3+ )-doped UCNPs as two independent reporters on two-color lateral flow strips, new records of limit of detection (LOD), 89 and 400 pg/mL, have been achieved for the ultrasensitive detection of prostate specific antigen (PSA) and ephrin type-A receptor 2 (EphA2) biomarkers, respectively, without crosstalk. The technique and device presented in this work suggests a broad scope of low-cost, rapid, and quantitative lateral flow assays in early detection of bioanalytes.

Highly Sensitive Biosensors Based on Biomolecules and Functional Nanomaterials Depending on the Types of Nanomaterials: A Perspective Review

“…Using the small-sized UCNPs with densely doped emitters, LFA biosensors were developed to detect PSA and type-A receptor 2 (EphA2). To detect target molecules, the sensing probes were combined with UCNPs which were a prostate cancer biomarker and pancreatic cancer biomarker [77]. To develop this biosensor, highly doped UCNPs composed of erbium (Er 3+ ) and thulium (Tm 3+ ) ions were synthesized to achieve an excellent brightness emission signal and sensitivity.…”

“…(b) A schematic of the electrochemical biosensor composed of Ti3C2-MXene (few-atom-thick layer of transition metal carbides, nitrides, or carbonitrides) for sensitive and reproducible carcinoembryonic antigen (CEA) detection, and cyclic voltammogram obtained by using fabricated electrochemical biosensor for detection of different concentrations of target molecules (reproduced with permission from Reference[75], published by Elsevier, 2018). (c) A schematic of the LFA biosensor based on highly doped upconverting NPs (UCNPs) to detect PSA and type-A receptor 2 (EphA2) with high sensitivity and selectivity, and photo and fluorescence intensities of testing areas of different concentrations of PSA and EphA2 (reproduced with permission from Reference[77], published by American Chemical Society, 2018).…”

Recent Trends in Nanomaterial-Based Biosensors for Point-of-Care Testing

“…For example, Tao's group developed quantum dot-based lateral flow immunoassays for detecting serumspecific IgE against Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae (Der-f) (Liang et al, 2020), which can detect serum-specific levels of IgE against Der-p and Derf as low as 0.093 and 0.087 IU/mL, respectively. Jin et al developed quantitative lateral flow immunoassays using highly doped UCNPs for the detection of prostate specific antigen (PSA) and ephrin type-A receptor 2 with detection limits of 89 and 400 pg/mL, respectively (He et al, 2018). Lateral flow tests are simple, economic and generally show results in around 5-20 min, which are widely used in medical diagnosis.…”

Highly Sensitive Chemiluminescence-Based Lateral Flow Immunoassay for Cardiac Troponin I Detection in Human Serum

“…To resolve this issue, many studies have employed sensitive labels [11][12][13][14][15][16][17]-i.e., catalytic labels, fluorescence dyes, magnetic particles, quantum dots, upconverting nanoparticles, and surface-enhanced Raman-scattering particles-and have enhanced the analytical sensitivity and quantitative capacity of LFAs. Among these approaches, enzyme-catalyzed LFAs paired with chemiluminescence (CL) detection, which involves the emission of a light signal when the excited intermediate chemicals return to the ground state, is considered to be a promising transduction modality for high-performance LFAs in that the CL method offers (i) no need for incident excitation light, (ii) a higher signal/noise ratio, (iii) and a more extensive dynamic range [11,18,19].…”