256
Q. Lv et al.
(AuNFs) for Raman signal enhancement, and used three specific ligands immobilization, including AS1411 aptamer, the RGD peptide, and anti-CD44 antibody
for cell adhesion. Two different phenotypes of breast cancer (MCF7 and MDAMB-231 cells) could be discriminated and imaged in mice, contributing to early
cancer diagnosis. This sensor allows non-invasive cancer phenotype identification
with low cross-reactivity and unique spectral-molecular signature, facilitating the
personalized medicine field [101]. Graphene has stable optical properties and sensitive Raman cross-section, which make it an ideal material for SERS sensor. Based
on these properties, the graphene-isolated-Au-nanocrystals (GIANs) were used to
establish SERS aptasensor for cancer cells detection, with the immobilization of
phospholipid-polyethylene glycol-linked MUC-1 aptamers. This SERS sensor can
identify cancer cells through targeting the overexpressed surface protein, with high
resolution multiplexed imaging and low background [102].
9.4.3 Aptamer-Based Microfluidic Cytosensors
The first aptamer-based microfluidics was developed for CTCs determination in
2009 by Tan’s group. In their work, the affinity-based device was based on a
poly(dimethylsiloxane) microchannel for the Sgs8 aptamer immobilization for the
CCRF-CEM cells capture, with about 95% purification efficiency. An optical microscope was coupled for target cells visualization [103]. This novel device integrates the
merits of microdevices as separation platform and aptamers as recognition elements,
facilitating CTCs isolation and purification. The dimension of the microchannel is
comparable to the size of CTCs, which benefits their interaction to improve the purification efficiency. Meanwhile, the fluid force within the microchannels could reduce
the non-specific adsorption of irrelevant components, further improving the isolation
efficiency.
The performance of microfluidics largely relies on two aspects: the microfluidic chip design and the multivalent aptamer functionalization strategy. For the
chip design, the microstructure was initially established within the microchannel
to enhance the capture ability and collision frequency [104]. Then, the nanostructures within the chips offer more area for aptamers immobilization and exhibit
increased local topographic interactions with the nanoscale surface components of
target cells. Therefore, the enhanced interaction between aptamers and target cells
further improves the CTCs isolation efficiency. For example, the inorganic and “soft”
nano-substrates were successfully utilized in aptamer-based microdevices for CTCs
capture efficiency improvement [105, 106]. Another key factor affecting microfluidic performance is the aptamer binding affinity. To solve this problem, multivalent
binding has been proved as an effective strategy, which can enhance the affinity by
several magnitudes. This strategy is based on the simultaneous interaction between
multiple ligands of one entity and multiple receptors of another [107]. For instance,
the aptamer cocktail had been immobilized on the Si nanowires-embedded microfluidic chip to capture diverse CTC phenotypes from clinical samples of non-small
Q. Lv et al.
(AuNFs) for Raman signal enhancement, and used three specific ligands immobilization, including AS1411 aptamer, the RGD peptide, and anti-CD44 antibody
for cell adhesion. Two different phenotypes of breast cancer (MCF7 and MDAMB-231 cells) could be discriminated and imaged in mice, contributing to early
cancer diagnosis. This sensor allows non-invasive cancer phenotype identification
with low cross-reactivity and unique spectral-molecular signature, facilitating the
personalized medicine field [101]. Graphene has stable optical properties and sensitive Raman cross-section, which make it an ideal material for SERS sensor. Based
on these properties, the graphene-isolated-Au-nanocrystals (GIANs) were used to
establish SERS aptasensor for cancer cells detection, with the immobilization of
phospholipid-polyethylene glycol-linked MUC-1 aptamers. This SERS sensor can
identify cancer cells through targeting the overexpressed surface protein, with high
resolution multiplexed imaging and low background [102].
9.4.3 Aptamer-Based Microfluidic Cytosensors
The first aptamer-based microfluidics was developed for CTCs determination in
2009 by Tan’s group. In their work, the affinity-based device was based on a
poly(dimethylsiloxane) microchannel for the Sgs8 aptamer immobilization for the
CCRF-CEM cells capture, with about 95% purification efficiency. An optical microscope was coupled for target cells visualization [103]. This novel device integrates the
merits of microdevices as separation platform and aptamers as recognition elements,
facilitating CTCs isolation and purification. The dimension of the microchannel is
comparable to the size of CTCs, which benefits their interaction to improve the purification efficiency. Meanwhile, the fluid force within the microchannels could reduce
the non-specific adsorption of irrelevant components, further improving the isolation
efficiency.
The performance of microfluidics largely relies on two aspects: the microfluidic chip design and the multivalent aptamer functionalization strategy. For the
chip design, the microstructure was initially established within the microchannel
to enhance the capture ability and collision frequency [104]. Then, the nanostructures within the chips offer more area for aptamers immobilization and exhibit
increased local topographic interactions with the nanoscale surface components of
target cells. Therefore, the enhanced interaction between aptamers and target cells
further improves the CTCs isolation efficiency. For example, the inorganic and “soft”
nano-substrates were successfully utilized in aptamer-based microdevices for CTCs
capture efficiency improvement [105, 106]. Another key factor affecting microfluidic performance is the aptamer binding affinity. To solve this problem, multivalent
binding has been proved as an effective strategy, which can enhance the affinity by
several magnitudes. This strategy is based on the simultaneous interaction between
multiple ligands of one entity and multiple receptors of another [107]. For instance,
the aptamer cocktail had been immobilized on the Si nanowires-embedded microfluidic chip to capture diverse CTC phenotypes from clinical samples of non-small