9 Aptamers for the Diagnosis of Malign Tumors
257
cell lung cancer (NSCLC) patients. Compared with a single aptamer, this aptamer
cocktail platform can offer a synergistic effect based on the concurrent recognitions,
providing better efficiency for CTCs capture [108].
The consensus has been reached that only capture and quantification of the CTCs
can’t offer sufficient information for cancer diagnosis, therapy, and understanding
[109]. Therefore, releasing captured CTCs for in-depth analysis has become a major
challenge [110]. The benefit of their controllably altered affinity, aptamers exhibit
prominent predominance for CTCs release and analysis. For example, aptamers are
quite sensitive to nuclease degradation, resulting in conformation disruption [111].
Additionally, the commonly used Au-thiol bonds for aptamers immobilization onto
Au substrate could be cutting off via competitive ligand exchange or electrochemical
reduction [112].
Recently, many aptamer-based microfluidic devices are fabricated successfully
for enumeration and in-depth analysis. For example, the MUC 1 aptamer-modified
gold nanofilm chip archived the LOD of 10 tumor cells in the blood sample, with the
LDI-MS (laser desorption-ionization mass spectrometry) coupled for further analysis [113] (Fig. 9.7a). Another two-dimensional microfluidic chip based on multiple
immobilized aptamers was designed to identify 16 CTC subpopulations through the
different expression levels of surface protein HER2 and EpCAM [114] (Fig. 9.7b).
Then, the same group further reported the biochemical phenotypes and functions
of these heterogeneous CTCs [116, 117]. Besides, the microfluidic chip utilizing
multifunctional aptamers can facilitate the CTC sequence analysis. A microfluidic device containing two orthogonal microchannels was designed for cancer cells
capture and genomic (gDNA) sequencing. The aptamers were immobilized within
one channel containing micropillars for cancer cells binding. The captured cells were
lysed and their gDNA was further isolated through physical entanglement within
another smaller dimensioned micropillar array. This device was used to sequence
ovarian and cervical cancer cells for TP53 gene mutations, exhibiting the reliability
for CTCs in-depth analysis [115] (Fig. 9.7c).
9.5 Tissue Section Imaging
The imaging techniques are still common methods for the detection and characterization of tumors and cancers, as well as assess their responses to therapeutic
intervention. The major imaging approaches include optical technique (bioluminescence and fluorescence), positron-emission tomography (PET), magnetic resonance
imaging (MRI), computed tomography (CT), ultrasound (US), and single-photon
emission computed tomography (SPECT). Suitable imaging probes require good
stability, low target-to-background-noise signals, and relative low toxicology [118].
Therefore, aptamers are considered as a potential candidate to construct probes,
due to their unique characteristics, including high affinity, specific recognition, low
immunogenicity, and smaller size (comparing with antibodies) [119]. For example,
aptamer-based probes exhibit brighter and superior targeted imaging for intracellular
257
cell lung cancer (NSCLC) patients. Compared with a single aptamer, this aptamer
cocktail platform can offer a synergistic effect based on the concurrent recognitions,
providing better efficiency for CTCs capture [108].
The consensus has been reached that only capture and quantification of the CTCs
can’t offer sufficient information for cancer diagnosis, therapy, and understanding
[109]. Therefore, releasing captured CTCs for in-depth analysis has become a major
challenge [110]. The benefit of their controllably altered affinity, aptamers exhibit
prominent predominance for CTCs release and analysis. For example, aptamers are
quite sensitive to nuclease degradation, resulting in conformation disruption [111].
Additionally, the commonly used Au-thiol bonds for aptamers immobilization onto
Au substrate could be cutting off via competitive ligand exchange or electrochemical
reduction [112].
Recently, many aptamer-based microfluidic devices are fabricated successfully
for enumeration and in-depth analysis. For example, the MUC 1 aptamer-modified
gold nanofilm chip archived the LOD of 10 tumor cells in the blood sample, with the
LDI-MS (laser desorption-ionization mass spectrometry) coupled for further analysis [113] (Fig. 9.7a). Another two-dimensional microfluidic chip based on multiple
immobilized aptamers was designed to identify 16 CTC subpopulations through the
different expression levels of surface protein HER2 and EpCAM [114] (Fig. 9.7b).
Then, the same group further reported the biochemical phenotypes and functions
of these heterogeneous CTCs [116, 117]. Besides, the microfluidic chip utilizing
multifunctional aptamers can facilitate the CTC sequence analysis. A microfluidic device containing two orthogonal microchannels was designed for cancer cells
capture and genomic (gDNA) sequencing. The aptamers were immobilized within
one channel containing micropillars for cancer cells binding. The captured cells were
lysed and their gDNA was further isolated through physical entanglement within
another smaller dimensioned micropillar array. This device was used to sequence
ovarian and cervical cancer cells for TP53 gene mutations, exhibiting the reliability
for CTCs in-depth analysis [115] (Fig. 9.7c).
9.5 Tissue Section Imaging
The imaging techniques are still common methods for the detection and characterization of tumors and cancers, as well as assess their responses to therapeutic
intervention. The major imaging approaches include optical technique (bioluminescence and fluorescence), positron-emission tomography (PET), magnetic resonance
imaging (MRI), computed tomography (CT), ultrasound (US), and single-photon
emission computed tomography (SPECT). Suitable imaging probes require good
stability, low target-to-background-noise signals, and relative low toxicology [118].
Therefore, aptamers are considered as a potential candidate to construct probes,
due to their unique characteristics, including high affinity, specific recognition, low
immunogenicity, and smaller size (comparing with antibodies) [119]. For example,
aptamer-based probes exhibit brighter and superior targeted imaging for intracellular