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Table 3 New technologies developed to detect prospective biomarkers in tear fluid

From: Tear-fluid-derived biomarkers of ocular complications in diabetes: a systematic review and meta-analysis

Reference

Technology

Brief description

Target disease

Analyte used

[53]

Flexible electrochemical sensor

A screen-printed carbon electrode was fabricated using polyimide film. The flexible electrode was prepared with FexCoyO4-rGO. Detection limit: 0.07 μM; sensitivity; 1510 μM cm−2 mA−1

Diabetes mellitus

Glucose

[54]

Optoelectrokinetic bead-based immunosensing technique

A combination of bead-based assays and rapid electrokinetic patterning. Limit of detection: 110 pg/mL

Diabetic retinopathy

Lipocalin-1

[61]

Open-well configuration optoelectrokinetic biochip

A combination of bead-based assays and rapid electrokinetic patterning built on an open-form biochip creates more flexibility in sample processing. Limit of detection: 2.9 pg/mL

N/A

Tumor necrosis factor-alpha

[57]

Aptamer triple-helix molecular switch probe

Makes use of electrochemical signal transduction and also uses a CHA/HCR nanomaterial- and enzyme-free signal amplification cascade strategy. Detection limit: 0.87 pM

Diabetic retinopathy

Lipocalin-1

[59]

InflammaDry

A 10-min immunoassay was used to detect levels of matrix metalloproteinase-9 > 40 ng/mL

Glaucoma

Matrix metalloproteinase-9

[60]

Rapid electrokinetic patterning chip

A combination of an optoelectrokinetic platform and a bead-based immunoassay. The limit of detection can be as low as 100 pg/mL

Diabetic retinopathy

Lipocalin-1; vascular endothelial growth factor

[58]

Diagnostic capillary with porous hydrogel

Developed to detect biomarkers in 16 min, the device works by attaching probe particles to capture particles and forming sandwiched immunocomplexes in the presence of the target biomarker. Limit of detection: 1 ng/mL

Diabetic retinopathy

Lipocalin-1

[56]

Immunofluorescence biosensor enhanced with a photonic crystal

Constructed by self-assembled nanoparticles that are coated with a thin layer of gold. Detects trace proteins suspended in tears. Limit of detection: 3 μg/mL

Diabetic retinopathy

Lipocalin-1

[55]

Diffusometric immunosensing technique with grafted gold nanoparticles

Technique was designed to detect small molecules for early disease diagnosis or low-abundance biomarkers. Fluorescent nanosized particles were conjugated with a capture antibody to selectively detect suspended target biomarkers. Limit of detection: 10 pg/mL

Diabetic retinopathy

Tumor necrosis factor-alpha

[37]

Ultrasensitive reusable electrochemical aptasensor

A hybridization chain reaction and CeO2 nanoparticles were used to create a cascade signal amplification strategy to detect VEGF. Limit of detection: 0.27 fg/mL

Diabetic retinopathy

Vascular endothelial growth factor

[64]

Fiber optic label-free biosensor

The system utilizes a fiber-optic ball resonator, fabricated with a CO2 laser splicer. Limit of detection: 240 ag/mL. The device can detect LCN-1 protein concentrations ranging up to 10 ng/mL

Diabetic retinopathy

Lipocalin-1

[63]

Colorimetric and fluorescent biosensors

Biosensors prepared from polyethylene glycol diacrylate-based inverse opal photonic crystal decorated with graphene oxide. Limit of detection: 6.7 × 10–5 mg/mL

Diabetic retinopathy

Lipocalin-1

[62]

Electrical biosensor chip

A multi-layer paper-based biosensor chip connected with a handheld printed circuit board to monitor the effectiveness of beta-2-microglobuin and lactoferrin in the contrived tear film. Range of detection from 0.001 to 1 ng/mL and 1 to 10 mg/mL, respectively

Dry eye syndrome; diabetic retinopathy

Lactoferrin, beta-2-microglobuin