Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor

This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16±1 µM (S/N=3), which is included in NAP physiological range (9–300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33±18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.

CNT and proteins for bioelectronics in personalized medicine

Cristina Boero, Sandro Carrara, Andrea Cavallini, Giovanni De Micheli

From their discovery, CNTs have increasingly attracted interest because of their peculiar electrical, mechanical, and chemical properties. In 1991, Sumio Iijima first observed and described in detail the atomic arrangement of this new type of carbon structure [1]. By a technique used for fullerene synthesis, he produced needle-like tubes at the cathode of an arc-discharge evaporator. From that time, carbon nanotubes have been used for many applications and represent one of the most typical building blocks used in nanotechnology. Their peculiarities include unique properties of field emission and electronic transport, higher mechanical strength with respect to other materials, and interesting chemical features. The use of CNTs has recently gained momentum in the development of electrochemical biosensors, since their utilization can create devices with enhanced sensitivity and detection limit capable of detecting compounds in concentrations comparable to those present in the human body. This chapter will review the most important features of carbon nanotubes, and present an example in which their application can enhance the detection of drugs and metabolites relevant in personalized medicine: P450 biosensors for therapeutic drug monitoring.

Cambridge University Press2015

Multiplexed nanoplasmonic biosensor for one-step simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine

Hatice Altug, Alexander Belushkin, Andrea Cavallini, Maria Soler Aznar

Development of rapid and multiplexed diagnostic tools is a top priority to address the current epidemic problem of sexually transmitted diseases. Here we introduce a novel nanoplasmonic biosensor for simultaneous detection of the two most common bacterial infections: Chlamydia trachomatis and Neisseria gonorrhoeae. Our plasmonic microarray is composed of gold nanohole sensor arrays that exhibit the extraordinary optical transmission (EOT), providing highly sensitive analysis in a label-free configuration. The integration in a microfluidic system and the precise immobilization of specific antibodies on the individual sensor arrays allow for selective detection and quantification of the bacteria in real-time. We achieved outstanding sensitivities for direct immunoassay of urine samples, with a limit of detection of 300 colony forming units (CFU)/mL for C. trachomatis and 1500 CFU/mL for N. gonorrhoeae. The multiplexing capability of our biosensor was demonstrated by analyzing different urine samples spiked with either C trachomatis or N. gonorrhoeae, and also containing both bacteria. We could successfully detect, identify and quantify the levels of the two bacteria in a one-step assay, without the need for DNA extraction or amplification techniques. This work opens up new possibilities for the implementation of point-of-care biosensors that enable fast, simple and efficient diagnosis of sexually transmitted infections.

2017

Early sepsis diagnosis via protein and miRNA biomarkers using a novel point-of-care photonic biosensor

Hatice Altug, Alexander Belushkin

y Sepsis is a condition characterized by a severe stage of blood-infection often leading to tissue damage, organ failure and finally death. Fast diagnosis and identification of the sepsis stage (sepsis, severe sepsis or septic shock) is critical for the patient's evolution and could help in defining the most adequate treatment in order to reduce its mortality. The combined detection of several biomarkers in a timely, specific and simultaneous way could ensure a more accurate diagnosis. We have designed a new optical point-of-care (POC) device based on a phase-sensitive interferometric biosensor with a label-free microarray configuration for potential high-throughput evaluation of specific sepsis biomarkers. The sensor chip, which relies on the use of metallic nanostructures, provides versatility in terms of biofunctionalization, allowing the efficient immobilization of different kind of receptors such as antibodies or oligonucleotides. We have focused on two structurally different types of biomarkers: proteins, including C-reactive protein (CRP) and Interleukin 6 (IL6), and miRNAs, using miRNA-16 as an example. Limits of Detection (LoD) of 18 mu g mL(-1), 88 mu g mL(-1) and 1 mM (6 mu g mL(-1)) have been respectively obtained for CRP, IL6 and miRNA-16 in individual assays, with high accuracy and reproducibility. The multiplexing capabilities have also been assessed with the simultaneous analysis of both protein biomarkers. (C) 2019 Elsevier B.V. All rights reserved.

ELSEVIER SCIENCE BV2019