Paper-Based Detection Device for Alzheimer’s Disease—Detecting β-amyloid Peptides (1–42) in Human Plasma

Abstract

The diagnosis of Alzheimer’s disease (AD) is frequently missed or delayed in clinical practice. To remedy this situation, we developed a screening, paper-based (P-ELISA) platform to detect β-amyloid peptide 1–42 (Aβ42) and provide rapid results using a small volume, easily accessible plasma sample instead of cerebrospinal fluid. The protocol outlined herein only requires 3 μL of sample per well and a short operating time (i.e., only 90 min). The detection limit of Aβ42 is 63.04 pg/mL in a buffer system. This P-ELISA-based approach can be used for early, preclinical stage AD screening, including screening for amnestic mild cognitive impairment (MCI) due to AD. It may also be used for treatment and stage monitoring purposes. The implementation of this approach may provide tremendous impact for an afflicted population and may well prompt additional and expanded efforts in both academic and commercial communities.

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

“…36,52,57,58 Tremendous studies have reported the ELISA application in detecting Ab levels in CSF, human plasma, and serum samples. [59][60][61][62][63][64] Numerous lab-based ELISA kits have now been available in the market with the detection range of 10 to 1000 pg mL À1 and procient of discriminating AD patients with healthy control with good sensitivity (80%) and moderate specicity (83.3%). 52,65 In spite of time-consuming and laborious issues of traditional ELISA, the alternative ELISA kits have been widely developed for amyloid detection, which include paper-based ELISA 63 and digital ELISA.…”

“…[59][60][61][62][63][64] Numerous lab-based ELISA kits have now been available in the market with the detection range of 10 to 1000 pg mL À1 and procient of discriminating AD patients with healthy control with good sensitivity (80%) and moderate specicity (83.3%). 52,65 In spite of time-consuming and laborious issues of traditional ELISA, the alternative ELISA kits have been widely developed for amyloid detection, which include paper-based ELISA 63 and digital ELISA. 66,67 Both of them are cost-effective, easy to operate, and portable and thus suitable for POC diagnostic approach.…”

Distance-based β-amyloid protein detection on PADs for the scanning and subsequent follow-up of Alzheimer's disease in human urine samples

“…23 Similarly, Hsuan Sung et al developed a paper-based enzyme-linked immunoassay sensor (P-ELISA). 24 Although these techniques offered high sensitivity, they still lacked the essential properties suitable for POC devices regrading AD screening. They required complicated procedures, a low-throughput screening assay, and large reagent consumption; for instance, immunoassays based on SPR and P-ELISA require on average 5 h and 90 min standard operating times.…”

Photooxidation-induced fluorescence amplification system for an ultra-sensitive enzyme-linked immunosorbent assay (ELISA)

“…The previous approaches to overcoming the sensitivity barrier was amplifying the signal to a detectable level. For example, digital ELISA confines fluorescent molecules, generated by enzymes, into reaction chambers of less than 50 fL (femtoliter) 4 – 6 , 8 , 10 , 11 , and plasmonic ELISA generates colorimetric signals with distinct tonality, as plasmonic nanoparticles are aggregated 12 – 16 . The bio-barcode technique also enhances sensitivity via DNA-aided signal amplification 17 – 21 and ECAS-CIA (enzyme-cascade-amplification strategy-colorimetric immunoassay) allows the detection of low-abundance proteins by coupling with enzyme cascade amplification 22 .…”