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Topics in Current Chemistry (2020) 378:35
for backup or remote processing of the results, which is highly demanded in modern
healthcare systems.
Recent advances in QD-based microfluidic paper devices and QD barcode POC
applications are discussed in more detail in subsequent sections.
5.1 QD‑Based Microfluidic Paper Devices
Paper-based devices can be classified into dipsticks assays, lateral flow assays
(LFAs) and microfluidic paper analytical devices (µPADs). The dipstick assays are
the simplest paper-based devices and are based on a paper strip pre-stored with reagents that is dipped into a sample to perform a chemical test (e.g. pH strips). LFAs
are the most widely reported form of paper devices (e.g. pregnancy test) [115]. The
basic structure of a lateral flow strip comprises four different parts that are fixed in
a backing card (Fig. 12a): a sample pad, on which the sample is dropped; a conjugation pad, on which labeled tags conjugated to the biorecognition elements are
immobilized; a reaction membrane, which contains test and control lines for reactions; and an absorbent pad, which reserves waste and prevents backflow. Briefly,
when a sample is placed onto the sample pad, the sample flows via capillary forces
towards the end of the strip. If the analyte is present, the immobilized bioconjugate
on the conjugation pad binds to the analyte and continues migrating along the test.
As the sample moves along the device, the binding reagents placed on the reaction
membrane bind to the analyte at the test line. Bioconjugates free of analyte finally
react with specific bioreceptors immobilized on the control line of the membrane
(Fig. 12b). µPADs are the most complex but most versatile paper devices [116]. In
these devices the formation of hydrophilic channels with hydrophobic barriers enables multidirectional and multidimensional flow that allows for complex bioassays
to be performed.
Most of the reported paper devices rely on the use of AuNPs as labels, with qualitative (naked-eye) or semi-quantitative colorimetric detection. The main limitations
of colorimetric detection of AuNPs include limited quantitative dynamic ranges and
low sensitivity, even with reader systems [117, 118]. In this context, the use of QDs
as fluorescence labels is becoming increasingly popular. Fluorescence detection is
a good choice to improve both the limit of detection and the dynamic range of colorimetric paper-based devices. However, an important drawback of fluorescence
detection in POC applications is the need for complex reader systems to interpret the
results.
QDs have been used as signal reporters in the development of different types of
paper-based biosensors. Sapountzi et al. [119] designed the first QD-based dipstick
for visual detection of nucleic acids and single nucleotide polymorphisms (SNPs) in
the human genomic using a common digital camera and a UV lamp for fluorescence
imaging. As low as 1.5 fmol levels of double-stranded DNA were clearly detected
by naked eye using CdSe/ZnS core–shell QDs as signal reporters. The dipstick performance was accurate and reproducible and was also successfully applied to real
sample analysis.
153
Reprinted from the journal
Topics in Current Chemistry (2020) 378:35
for backup or remote processing of the results, which is highly demanded in modern
healthcare systems.
Recent advances in QD-based microfluidic paper devices and QD barcode POC
applications are discussed in more detail in subsequent sections.
5.1 QD‑Based Microfluidic Paper Devices
Paper-based devices can be classified into dipsticks assays, lateral flow assays
(LFAs) and microfluidic paper analytical devices (µPADs). The dipstick assays are
the simplest paper-based devices and are based on a paper strip pre-stored with reagents that is dipped into a sample to perform a chemical test (e.g. pH strips). LFAs
are the most widely reported form of paper devices (e.g. pregnancy test) [115]. The
basic structure of a lateral flow strip comprises four different parts that are fixed in
a backing card (Fig. 12a): a sample pad, on which the sample is dropped; a conjugation pad, on which labeled tags conjugated to the biorecognition elements are
immobilized; a reaction membrane, which contains test and control lines for reactions; and an absorbent pad, which reserves waste and prevents backflow. Briefly,
when a sample is placed onto the sample pad, the sample flows via capillary forces
towards the end of the strip. If the analyte is present, the immobilized bioconjugate
on the conjugation pad binds to the analyte and continues migrating along the test.
As the sample moves along the device, the binding reagents placed on the reaction
membrane bind to the analyte at the test line. Bioconjugates free of analyte finally
react with specific bioreceptors immobilized on the control line of the membrane
(Fig. 12b). µPADs are the most complex but most versatile paper devices [116]. In
these devices the formation of hydrophilic channels with hydrophobic barriers enables multidirectional and multidimensional flow that allows for complex bioassays
to be performed.
Most of the reported paper devices rely on the use of AuNPs as labels, with qualitative (naked-eye) or semi-quantitative colorimetric detection. The main limitations
of colorimetric detection of AuNPs include limited quantitative dynamic ranges and
low sensitivity, even with reader systems [117, 118]. In this context, the use of QDs
as fluorescence labels is becoming increasingly popular. Fluorescence detection is
a good choice to improve both the limit of detection and the dynamic range of colorimetric paper-based devices. However, an important drawback of fluorescence
detection in POC applications is the need for complex reader systems to interpret the
results.
QDs have been used as signal reporters in the development of different types of
paper-based biosensors. Sapountzi et al. [119] designed the first QD-based dipstick
for visual detection of nucleic acids and single nucleotide polymorphisms (SNPs) in
the human genomic using a common digital camera and a UV lamp for fluorescence
imaging. As low as 1.5 fmol levels of double-stranded DNA were clearly detected
by naked eye using CdSe/ZnS core–shell QDs as signal reporters. The dipstick performance was accurate and reproducible and was also successfully applied to real
sample analysis.
153
Reprinted from the journal