Effective pathogen detection is an essential prerequisite for the prevention and treatment of infectious diseases. Despite recent advances in biosensors, infectious diseases remain a major cause of illnesses and mortality throughout the world. For instance in developing countries, infectious diseases account for over half of the mortality rate. Pathogen detection platforms provide a fundamental tool in different fields including clinical diagnostics, pathology, drug discovery, clinical research, disease outbreaks, and food safety. Microfluidic lab-on-a-chip (LOC) devices offer many advantages for pathogen detection such as miniaturization, small sample volume, portability, rapid detection time and point-of-care diagnosis. This review paper outlines recent microfluidic based devices and LOC design strategies for pathogen detection with the main focus on the integration of different techniques that led to the development of sample-to-result devices. Several examples of recently developed devices are presented along with respective advantages and limitations of each design. Progresses made in biomarkers, sample preparation, amplification and fluid handling techniques using microfluidic platforms are also covered and strategies for multiplexing and high-throughput analysis, as well as point-of-care diagnosis, are discussed.
The size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd 2 O 3 ) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r 1 , r 2 ) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd 2 O 3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd 2 O 3 nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd 3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG-Gd 2 O 3 and PEG-silane-SPGO (Gd 2 O 3 , < 40 nm diameter). The small and narrow size distribution of US-Gd 2 O 3 was confirmed with TEM (∼3nm)andDLS.PEG-silane-US-Gd 2 O 3 relaxation parameters were twice as high as for Gd-DTPA and the r 2 /r 1 ratio was 1.4. PEG-silane-SPGO gave low r 1 relaxivities and high r 2 /r 1 ratios, less compatible with positive contrast agent requirements. Higher r 1 were obtained with PEG-silane in comparison to DEG-Gd 2 O 3 . Treatment of DEG-US-Gd 2 O 3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd 2 O 3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.
The ambition of lab-on-a-chip (LOC) systems to achieve chip-level integration of a complete analytical process capable of performing a complex set of biomedical protocols is hindered by the absence of standard fluidic components able to be assembled. As a result, most microfluidic platforms built to date are highly specialized and designed to fulfill the requirements of a single particular application within a limited set of operations. Electrowetting-on-dielectric (EWOD) digital microfluidic technology has been recently introduced as a new methodology in the quest for LOC systems. Herein, unit volume droplets are manipulated along electrode arrays, allowing a microfluidic function to be reduced to a set of basic operations. The highly reprogrammable architecture of these systems can satisfy the needs of a diverse set of biochemical assays and ensure reconfigurability, flexibility and portability between different categories of applications and requirements. While important progress was made over past years in the fabrication, miniaturization and function programming of the basic EWOD fluidic operations, the success of this technology will in great part depend on the ability of researchers to couple or integrate digital microfluidics to detection approaches that can make the system competitive for LOC applications. The detection techniques should be able to circumvent the limitations of hydrophobic surfaces and exploit the advantages of the array format, high droplet transport speeds and rapid mixing schemes. This review provides an in-depth look at recent developments for the coupling and integration of detection techniques with digital microfluidic platforms for bio-chemical applications.
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