Nucleic acid analysis on paper substrates (NAAPs): an innovative tool for Point of Care (POC) infectious disease diagnosis.

The cost-effective rapid diagnosis of infectious diseases is an essential and important factor for curing such diseases in the global public health care picture. Owing to poor infrastructure and lack of sanitation, these diseases have an extreme impact on remote and rural areas, especially in developing countries, and there are unresolved challenges. Molecular diagnosis, such as nucleic acid analysis, plays a key role in the significant treatment of numerous infectious diseases. Current molecular diagnostic assays require a sophisticated laboratory setup with expensive components. Molecular diagnosis on a microfluidic point-of-care (POC) platform is attractive to researchers for disease detection with proper prevention. Compared to various microfluidic substrate materials, paper-based POC technologies offer significant cost-effective solutions over high-cost clinical instruments to fill the gap between the needs of users and affordability. Low-cost paper-based microfluidic POC technologies provide portable and disposable diagnostic systems for multiple disease detection that may be extremely useful in remote areas. This article presents a critical review of paper-based microfluidic device technology which has become an imminent platform to adjust the current health scenario for the detection of diseases using different stages of nucleic acid analysis, such as extraction, amplification and detection of nucleic acid, with future perspectives for paper substrates.

Anatomical variations in cortical bone surface permeability: Tibia versus femur.

Cortical bone surfaces (periosteal and endosteal) exhibit differential (re)modelling response to mechanical loading. This poses a serious challenge in establishing an in silico model to predict site-specific new bone formation as a function of mechanical stimulus. In this regard, mechanical loading-induced fluid motion in lacunar-canalicular system (LCS) is assumed osteogenic. Micro-architectural properties, especially permeability regulate canalicular fluid motion within the bone. The knowledge of these properties is required to compute flow distribution. Along the same line, it is possible that cortical surfaces may experience differential fluid distribution due to anatomical variations in microarchitectural properties which may induce distinct new bone response at cortical surfaces. Nevertheless, these properties are not well reported for cortical surfaces in the literature. Accordingly, the present study aims to measure microarchitectural properties especially permeability at different anatomical locations (medial, lateral, anterior, and posterior) of periosteal and endosteal surfaces using nanoindentation. A standard poroelastic optimization technique was used to estimate permeability, shear modulus, and Poisson's ratio. The properties are also compared for two weight-bearing bones i.e. tibia and femur. Endosteal surface was found more permeable as compared to the periosteal surface. Tibial endosteal surface had shown greater permeability values at most of the anatomical locations as compared to femoral endosteal surface. The outcomes may be used to precisely predict site-specific osteogenesis in cortical bone as a function of canalicular flow distribution. This work may ultimately be beneficial in designing the loading parameters to stimulate desired new bone response for the prevention and the cure of bone loss.

Signalling molecule transport analysis in lacunar-canalicular system.

Mechanical loading-induced fluid flow in lacunar-canalicular space (LCS) of bone excites osteocyte cells to release signalling molecules which initiate osteo-activities. Theoretical models considered canaliculi as a uniform and symmetrical space/channel in bone. However, experimental studies reported that canalicular walls are irregular and curvy resulting in inhomogeneous fluid motion which may influence the molecular transport. Therefore, a new mathematical model of LCS with curvy canalicular walls is developed to characterize cantilever bending-induced canalicular flow behaviour in terms of pore-pressure, fluid velocity, and streamlines. The model also analyses the mobility of signalling molecules involved in bone mechanotransduction as a function of loading frequency and permeability of LCS. Inhomogeneous flow is observed at higher loading frequency which amplifies mechanotransduction; nevertheless, it also promotes trapping of signalling molecules. The effects of shape and size of signalling molecules on transport behaviour are also studied. Trivially, signalling molecules larger in size and weight move slower as compared to molecules small in size and weight which validates the findings of the present study. The outcomes will ultimately be useful in designing better biomechanical exercise in combination with pharmaceutical agents to improve the bone health.

MEMS impedance flow cytometry designs for effective manipulation of micro entities in health care applications.

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34+), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.