ABSTRACT
Minimal residual disease (MRD) offers a highly independent prognostic factor for leukemia patients. However, challenges confronting conventional MRD assays are high invasiveness, as well as limited detection sensitivity and clinical applicability. Inspired by the self-adaptive skeleton and multiple suckers or tendrils of climbing plants, a biomimetic Multivalent Aptamer Nanoclimber (MANC)-functionalized microfluidic chip (MANC-Chip) is reported for minimally invasive, highly sensitive and clinically applicable MRD detection in the peripheral blood of T-cell acute lymphoblastic leukemia patients. The MANCs are synthesized by a simple co-polymerization reaction. Due to their flexible structure and cooperative multivalent effect, MANCs dramatically enhance the binding affinity of aptamers targeting leukemia cells. A deterministic lateral displacement-patterned microfluidic chip is designed to further increase the collision probability between MANCs and leukemia cells. Benefiting from the synergistic effect of multivalent binding and enhanced collision, a high capture efficiency of 92.2% for leukemia cells is achieved. Moreover, the captured leukemia cells can be released with high efficiency of 88.9% and high viability of 93.8% via nuclease treatment prior to downstream analysis. Overall, the excellent features of MANC-Chip make it very useful for precise detection of MRD and better understanding of leukemia.
Subject(s)
Leukemia , Microfluidics , Biomimetics , Humans , Leukemia/diagnosis , Neoplasm, Residual , Oligonucleotides , PrognosisABSTRACT
DNA hydrogels have received considerable attention in analytical science, however, some limitations still exist in the applications of intelligent hydrogels. In this paper, we describe a way to prepare gel film in a capillary tube based on the thermal reversible principle of DNA hydrogel and the principle of capillary action. Because of the slight change in the internal structure of gel, its permeability can be increased by the addition of some specific targets. The capillary behavior is thus changed due to the different permeability of the hydrogel film. The duration time of the target solution flowing through the capillary tube with a specified length is used to quantify this change. With this proposed method, ultra-trace DNA hydrogel (0.01 µL) is sufficient to realize the sensitive detection of cocaine without the aid of other instruments, which has a low detection limit (1.17 nM) and good selectivity.
Subject(s)
Aptamers, Nucleotide , Capillary Tubing , Cocaine/analysis , Hydrogels , Biosensing Techniques , Cocaine/urine , Equipment Design , Humans , Limit of Detection , PermeabilityABSTRACT
ortho-Phthalaldehyde (OPA) phosphoramidite with high reaction activity was designed and synthesized for labelling oligodeoxynucleotides (DNA). The DNA modified with OPA (OPA-DNA) can covalently couple with native proteins rapidly and efficiently via a condensation reaction with the formation of phthalimidines, which provides a highly efficient method for bioconjugation of DNA and native proteins under physiological conditions.
Subject(s)
Cytochromes c/chemistry , Indicators and Reagents/chemistry , Muramidase/chemistry , Oligodeoxyribonucleotides/chemistry , Streptavidin/chemistry , o-Phthalaldehyde/analogs & derivatives , o-Phthalaldehyde/chemistry , Cross-Linking Reagents/chemistry , DNA/chemistry , Fluorescence , Indicators and Reagents/chemical synthesis , Maleimides/chemistry , Oligodeoxyribonucleotides/chemical synthesis , o-Phthalaldehyde/chemical synthesisABSTRACT
Little is known regarding plaque distribution, composition, and the association with inflammation in type 2 diabetes mellitus (DM2). This study aimed to assess the relationship between coronary plaque subtypes and high-sensitivity C-reactive protein levels. Coronary CTA were performed in 98 symptomatic DM2 patients and 107 non-DM2 patients using a 256-slice CT. The extent and types of plaque as well as luminal narrowing were evaluated. Patients with DM2 were more likely to have significant stenosis (>50%) with calcified plaques in at least one coronary segment (p < 0.01); the prevalence rates of diffuse calcified plaques in the DM2 and non-DM2 groups were 31.6% and 4.7%, respectively (p < 0.01). Plasma hs-CRP levels in DM2 with calcified plaques were higher compared with values obtained for the non-DM2 group (p < 0.01). In conclusion, combination of coronary CTA and hs-CRP might improve risk stratification in symptomatic DM2 patients.
