14 Perspectives of Aptamers for Medical Applications
411
properties to potentially supersede antibodies in biosensor, as aptamers are smaller in
size, cheaper for synthesis, and can target-induce structural conformational change
which is expedient for flexible assay configuration. Combined with fluorescence,
electrochemical, surface plasmon resonance, and colorimetric-based measurements,
aptamer-based biosensor can be used in many fields of diagnostic clinical scenarios.
14.3.1.1 Diabetes Monitoring
Diabetes is a complex immune disorder that requires extensive medical care beyond
glycemic control [29]. The global diabetes prevalence in 2019 is estimated to be
9.3% (463 million people) and will rise to 10.2% (578 million) by 2030 and 10.9%
(700 million) by 2045 [30]. Blood glycated hemoglobin (HbA1c) levels reflecting
average glucose concentrations over the past three months are fundamental for the
diagnosis, monitoring, and risk assessment of diabetes. HbA1c levels are used to
guide the choice of therapy for patients with diabetes as well, with the goals <7.0% or
even <6.5% recommended for effective treatment of diabetes. Moreover, individuals
with HbA1c levels of 5.7–6.4% are referred to as having “pre-diabetes,” indicating
an increased risk for the future development of this disease. Thus, the precise and
accurate measurement of HbA1c can allow for the diagnosis of the earlier stages of
diabetes, at which point its progression into a serious ailment can be thwarted.
Lin et al. [31] screen a HbA1c-specific aptamer (72mer) by a SELEX chip utilizing
a combination of magnetic beads and microfluidic technique (Fig. 14.1). The HbA1cspecific aptamer bound to HbA1c but not other Hb molecular, the sequence of HbA1c
aptamer is 5
-GGC AGG AAG ACA AAC ACA TCG TCG CGG CCT TAG GAG
GGG CGG ACG GGGGGG GGC GTT GGT CTG TGG TGC TGT-3
, the property of
this aptamer was validated with an HbA1c aptamer-antibody sandwich immunoassay.
A linear relationship was found within the range of HbA1c 4.0–14.5%, which met
the diagnostic criteria of diabetes (the diagnostic criteria of the HbA1c in healthy
adults is within the range of 4.0–6.0%, with values 6.5% or higher to diagnose
diabetes); Chang et al. [32] further verified the HbA1c-specific aptamer in human
whole blood in an integrated microfluidic system. The calibration curve of HbA1c
represents reasonably a linear relationship (R2 = 0.966) for HbA1cconcentrations
between 0.46 and 1.85 g/dL. All detection was fulfilled within 25 min which shows its
potential to become a promising method for POCTs in long-term diabetes monitoring
(Fig. 14.2).
Glycated Albumin (GA) is another forefront of diabetic diagnosis for both control
and diagnosis of diabetic patient. It reflects glycemic status over the last 3 weeks and
can be used as an accurate marker especially in the pathologies including hemolytic
anemia and deficiency anemia of diabetic patients, in either situation, HbA1c level
could be unreliable [33]. Ghosh et al. [34] synthesized a molecular beacon, where
the GA aptamer (23mer) is attached to the quantum dot on one end and Au nanoparticle quencher on the other end for the detection of GA. The aptamers of GA were
modified on both ends with an amine group on the 5
and a Thiol group on the 3
411
properties to potentially supersede antibodies in biosensor, as aptamers are smaller in
size, cheaper for synthesis, and can target-induce structural conformational change
which is expedient for flexible assay configuration. Combined with fluorescence,
electrochemical, surface plasmon resonance, and colorimetric-based measurements,
aptamer-based biosensor can be used in many fields of diagnostic clinical scenarios.
14.3.1.1 Diabetes Monitoring
Diabetes is a complex immune disorder that requires extensive medical care beyond
glycemic control [29]. The global diabetes prevalence in 2019 is estimated to be
9.3% (463 million people) and will rise to 10.2% (578 million) by 2030 and 10.9%
(700 million) by 2045 [30]. Blood glycated hemoglobin (HbA1c) levels reflecting
average glucose concentrations over the past three months are fundamental for the
diagnosis, monitoring, and risk assessment of diabetes. HbA1c levels are used to
guide the choice of therapy for patients with diabetes as well, with the goals <7.0% or
even <6.5% recommended for effective treatment of diabetes. Moreover, individuals
with HbA1c levels of 5.7–6.4% are referred to as having “pre-diabetes,” indicating
an increased risk for the future development of this disease. Thus, the precise and
accurate measurement of HbA1c can allow for the diagnosis of the earlier stages of
diabetes, at which point its progression into a serious ailment can be thwarted.
Lin et al. [31] screen a HbA1c-specific aptamer (72mer) by a SELEX chip utilizing
a combination of magnetic beads and microfluidic technique (Fig. 14.1). The HbA1cspecific aptamer bound to HbA1c but not other Hb molecular, the sequence of HbA1c
aptamer is 5
-GGC AGG AAG ACA AAC ACA TCG TCG CGG CCT TAG GAG
GGG CGG ACG GGGGGG GGC GTT GGT CTG TGG TGC TGT-3
, the property of
this aptamer was validated with an HbA1c aptamer-antibody sandwich immunoassay.
A linear relationship was found within the range of HbA1c 4.0–14.5%, which met
the diagnostic criteria of diabetes (the diagnostic criteria of the HbA1c in healthy
adults is within the range of 4.0–6.0%, with values 6.5% or higher to diagnose
diabetes); Chang et al. [32] further verified the HbA1c-specific aptamer in human
whole blood in an integrated microfluidic system. The calibration curve of HbA1c
represents reasonably a linear relationship (R2 = 0.966) for HbA1cconcentrations
between 0.46 and 1.85 g/dL. All detection was fulfilled within 25 min which shows its
potential to become a promising method for POCTs in long-term diabetes monitoring
(Fig. 14.2).
Glycated Albumin (GA) is another forefront of diabetic diagnosis for both control
and diagnosis of diabetic patient. It reflects glycemic status over the last 3 weeks and
can be used as an accurate marker especially in the pathologies including hemolytic
anemia and deficiency anemia of diabetic patients, in either situation, HbA1c level
could be unreliable [33]. Ghosh et al. [34] synthesized a molecular beacon, where
the GA aptamer (23mer) is attached to the quantum dot on one end and Au nanoparticle quencher on the other end for the detection of GA. The aptamers of GA were
modified on both ends with an amine group on the 5
and a Thiol group on the 3