Bio-inspired microfluidics: A review.

Biomicrofluidics, a subdomain of microfluidics, has been inspired by several ideas from nature. However, while the basic inspiration for the same may be drawn from the living world, the translation of all relevant essential functionalities to an artificially engineered framework does not remain trivial. Here, we review the recent progress in bio-inspired microfluidic systems via harnessing the integration of experimental and simulation tools delving into the interface of engineering and biology. Development of "on-chip" technologies as well as their multifarious applications is subsequently discussed, accompanying the relevant advancements in materials and fabrication technology. Pointers toward new directions in research, including an amalgamated fusion of data-driven modeling (such as artificial intelligence and machine learning) and physics-based paradigm, to come up with a human physiological replica on a synthetic bio-chip with due accounting of personalized features, are suggested. These are likely to facilitate physiologically replicating disease modeling on an artificially engineered biochip as well as advance drug development and screening in an expedited route with the minimization of animal and human trials.

Targeting Magnetic Nanoparticles in Physiologically Mimicking Tissue Microenvironment.

Magnetic nanoparticles as drug carriers, despite showing immense promises in preclinical trials, have remained to be only of limited use in real therapeutic practice primarily due to unresolved anomalies concerning their grossly contrasting controllability and variability in performance in artificial test benches as compared to human tissues. To circumvent the deficits of reported in vitro drug testing platforms that deviate significantly from the physiological features of the living systems and result in this puzzling contrast, here, we fabricate a biomimetic microvasculature in a flexible tissue phantom and demonstrate distinctive mechanisms of magnetic-field-assisted controllable penetration of biocompatible iron oxide nanoparticles across the same, exclusively modulated by tissue deformability, which has by far remained unraveled. Our experiments deciphering the transport of magnetic nanoparticles in a blood analogue medium unveil a decisive interplay of the flexibility of the microvascular pathways, magnetic pull, and viscous friction toward orchestrating the optimal vascular penetration and targeting efficacy of the nanoparticles in colorectal tissue-mimicking bioengineered media. Subsequent studies with biological cells confirm the viability of using localized magnetic forces for aiding nanoparticle penetration within cancerous lesions. We establish nontrivially favorable conditions to induce a threshold force for vascular rupture and eventual target of the nanoparticles toward the desired extracellular site. These findings appear to be critical in converging the success of in vitro trials toward patient-specific targeted therapies depending on personalized vascular properties obtained from medical imaging data.

Cytological, histochemical, and ultrastructural study of human foetal liver of various gestation with future implications in segmental resection: an anatomical perspective.

The liver is the largest gland of the gastrointestinal tract having both exocrine and endocrine functions. Developmentally it arises as a ventral outgrowth from the gut endoderm during 3rd week of intrauterine life. The foetal liver is very important because of its synthetic and hemopoietic potential. The present work aimed to see the detailed histogenesis and development of the foetal liver by cytological, immunohistochemical and ultrastructural study. The liver tissue of nine aborted foetuses of various gestational age were studied. For cytology: special stains like Masson trichrome, periodic acid Schiff and reticulin were used, immunohistochemical staining was performed with triple antibodies (c-myc, Ki-67 and Ber-H2), and for ultrastructure: aluminium mounted specimens were coated with gold and argon gas and observed under scanning electron microscopy (EM). Cytology and immunohistochemistry showed the development of duct patterns and hemopoietic patterns in all stages of fetogenesis. The ductal plate was marked by the layer of dark brown staining cells at the edge of two portal tracts. The haemopoietic cells with sinusoids and aggregation of hepatocytes were observed in the early weeks of gestation. EM showed tree-like branching of a portal canal depicting hepatic segmentation of foetal liver. The organizational changes in lobular pattern, duct pattern, and microstructure of liver during fetogenesis are very crucial to achieve the adult morphology in feature. Histogenesis of the foetal liver follows a multistep process depending upon the gestational age, any deviation from normalcy may lead to structural and functional abnormality later in life.

Immunohematological and Clinical Characterization of Complement and Non-Complement Associated Warm Autoimmune Haemolytic Anemia and Risk Factors Predicting their Occurrences.

Antigen - antibody complexes on heavily coated red cells in Warm autoimmune haemolytic anemia (WAIHA) often activates the complement pathway and red cells bound C3 complement component are encountered in complement associated WAIHA (CWAIHA). Patients belonging to CWAIHA and non-complement associated WAIHA (NCWAIHA) may demographically, clinically and immunohematologically behave differently therefore we planned to study the clinical and immunohematological characteristics of CWAIHA and NCWAIHA with emphasis to various potential factors associated with CWAIHA. The prospective study included 229 patients of WAIHA. Complete DAT evaluation was performed in all these patients. Details of patients and their hematological and biochemical parameters were obtained from patient file and Hospital Information System. In vivo hemolysis was documented as per the criteria established by previous workers. Statistical analysis was done using SPSS statistical package. Of the total 229 patients of WAIHA, 83 (36.2%) belonged to the complement associated WAIHA group. A total of 146 (63.8%) patients were females of which 43 (29.4%) had CWAIHA. The median age of WAIHA patients was 37 years. A total of 46 (56.1%) patients above age 40 years suffered from CWAIHA. Where secondary WAIHA was found in 121 (52.8%) patients; more than half (61.4%) with CWAIHA had underlying aetiology. Over 95% of patients in both categories presented with weakness and pallor. Strong DAT (> 2 +) was observed in 86.7% of CWAIHA patients. Factors like gender, age, aetiology and DAT IgG dilution were independent risk factors for CWAIHA. DAT remained positive even at the end of 10 months of successful treatment. We conclude that detailed characterization of WAIHA with particular emphasis to complement and non-complement associated WAIHA is essential to evaluate the disease characters, immunological behaviours, prognosis and therapeutic management. Moreover an understanding of the risk factors of CWAIHA will help physicians / hematologists and immunohematologists to manage WAIHA more prudently and solicitously.

A Comprehensive Study of the Bridge Site and Substrate Relaxation Asymmetry for Methanethiol Adsorption on Au(111) at Low Coverage.

We use dispersion-corrected density functional theory to explore the bridge-site asymmetry for methanethiol adsorbed on Au(111) with two different S-C bond orientations. We attribute the asymmetry to the intrinsic character of the Au(111) surface rather than the adsorbate. The preference for bridge-fcc versus bridge-hcp SCH3 adsorption sites is controlled by the S-C bond orientation. The system energy difference favors the bridge-fcc site by 8.1 meV on the unrelaxed Au(111) surface. Relaxing the Au substrate increased this energy difference to 26.1 meV. This asymmetry is also reflected in the atomic displacement of the relaxed Au surface. Although in both cases, the bridge-site Au atoms shift away from the fcc 3-fold hollow site, the motion is greater for the bridge-fcc allowing a more favorable geometry for the sulfur atom to bond to the bridging atoms. We confirm that the adsorption energy is strongly dependent on the S-C bond orientation and position, which can be understood in terms of a simple coordination geometry model. This work has important implications for alkanethiol surface diffusion and the structure of their self-assembled monolayers.

Interaction of the (2√3 × 3)rect. Adsorption-Site Basis and Alkyl-Chain Close Packing in Alkanethiol Self-Assembled Monolayers on Au(111): A Molecular Dynamics Study of Alkyl-Chain Conformation.

We show that the adsorption site basis of the (2√3 × 3)rect. phase of n-alkanethiol self-assembled monolayers plays a key role in determining the molecular conformation of the close-packed alkyl chains. Ten proposed reconstructed Au-S interfaces are used to explore the minimized energy alkyl-chain packing of n-decanethiol molecules using molecular dynamics with the all-atom description. In this comparative study, all models have the same alkyl-chain surface density of four molecules per unit cell; thus, differences are due to the headgroup spacing within the 4-molecule basis as opposed to the average surface density. We demonstrate for the first time the 4-molecule-basis twist structure driven by the packing of alkanethiol molecules in a large simulation box (100 molecules, 25 unit cells) using molecular dynamics. Our results validate the prediction put forward by Mar and Klein that to achieve the 4-molecule-basis twist symmetry observed by the experiment, the headgroups must deviate from the high-symmetry (√3 × âˆš3)R30° sites. The key structural parameters: tilt, twist, and end-group height, as well as their spatial order, are compared with experimental results, which we show is a highly sensitive approach that can be used to vet proposed Au-S interfacial models.

Collective dynamics of red blood cells on an in vitro microfluidic platform.

Understanding the dynamics of blood flow in physiologically relevant confinements turns out to be an outstanding proposition in biomedical research. Despite the large number of studies being reported to theoretically elucidate the dynamics of red blood cells (RBCs) in confined geometries, in vitro experimental studies unveiling the implications of the collective dynamics of red blood cells in physiologically relevant bio-mimetic microfluidic channels remain elusive. Here, we investigate the implications of complex dynamvic interactions between the whole blood and a deformable channel wall fabricated using a hydrogel matrix. For a range of flow rates, we map the trajectories of the RBCs for varying levels of softness of the microchannel wall. We compare these scenarios with the reference cases of rigid polydimethylsiloxane (PDMS) channels. Our results reveal that the smallest channels investigated herein exhibit the most intricate interactions between the collective dynamics of the RBC and the wall flexibility, attributable to confinement-induced hydrodynamic interactions in the presence of spatially varying shear rates. These results may open up new paradigms in conceptual understanding of in vivo dynamics of blood flow through simple in vitro experiments on a simple microfluidic platform.

Two-dimensional collagen-graphene as colloidal templates for biocompatible inorganic nanomaterial synthesis.

In this study, natural graphite was first converted to collagen-graphene composites and then used as templates for the synthesis of nanoparticles of silver, iron oxide, and hydroxyapatite. X-ray diffraction did not show any diffraction peaks of graphene in the composites after inorganic nucleation, compared to the naked composite which showed (002) and (004) peaks. Scanning electron micrographs showed lateral gluing/docking of these composites, possibly driven by an electrostatic attraction between the positive layers of one stack and negative layers of another, which became distorted after inorganic nucleation. Docking resulted in single layer-like characteristics in certain places, as seen under transmission electron microscopy, but sp2/sp3 ratios from Raman analysis inferred three-layer composite formation. Strain-induced folding of these layers into uniform clusters at the point of critical nucleation, revealed beautiful microstructures under scanning electron microscopy. Lastly, cell viability studies using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed the highest cell viability for the collagen-graphene-hydroxyapatite composites. In this manner, this study provided - to the field of nanomedicine - a new process for the synthesis of several nanoparticles (with low toxicity) of high interest for numerous medical applications.

Optimizing superparamagnetic iron oxide nanoparticles as drug carriers using an in vitro blood-brain barrier model.

In the current study, an optimized in vitro blood-brain barrier (BBB) model was established using mouse brain endothelial cells (b.End3) and astrocytes (C8-D1A). Before measuring the permeability of superparamagnetic iron oxide nanoparticle (SPION) samples, the BBB was first examined and confirmed by an immunofluorescent stain and evaluating the transendothelial electrical resistance. After such confirmation, the permeability of the following five previously synthesized SPIONs was determined using this optimized BBB model: 1) GGB (synthesized using glycine, glutamic acid, and bovine serum albumin [BSA]), 2) GGC (glycine, glutamic acid, and collagen), 3) GGP (glycine, glutamic acid, and polyvinyl alcohol), 4) BPC (BSA, polyethylene glycol, and collagen), and 5) CPB (collagen, polyvinyl alcohol, and BSA). More importantly, after the permeability test, transmission electron microscopy thin section technology was used to investigate the mechanism behind this process. Transmission electron microscopy thin section images supported the hypothesis that collagen-coated CPB SPIONs displayed better cellular uptake than glycine and glutamine acid-coated GGB SPIONs. Such experimental data demonstrated how one can modify SPIONs to better deliver drugs to the brain to treat a wide range of neurological disorders.

Clinical and serological characterization of cold agglutinin syndrome in a Tertiary Care Hospital in Eastern India.

BACKGROUND AND AIM: Cold agglutinin syndrome (CAS) primary or secondary represents approximately 16-32% of autoimmune hemolytic anemia cases. Most patients present with mild, chronic hemolytic anemia with exacerbation of the condition in the cold environment. Red cell transfusions are only indicated when there is a life-threatening anemia causing crisis. We studied the clinical and serological characterization of CAS with the aim that the information gained from this study would help in proper diagnosis and management of these patients. MATERIALS AND METHODS: The prospective study included nine patients who were admitted with severe anemia. Detailed work-up were conducted to establish the diagnosis, severity of in vivo hemolysis and transfusion management. RESULTS: All patients presented with pallor, weakness, fatigue and painful fingers and toes with exacerbation of symptoms in winter months. Secondary CAS was observed in three patients suffering from malignant lymphoma. Red cells of all patients were coated with complements (C3) more specifically C3d. In one patient suffering from malignant lymphoma, the cold autoagglutinin titer was as high as 4096. Autoantibody in seven patients was specific to "I" antigen and one to "i" antigen. CONCLUSIONS: We conclude that detailed clinical and serological characterization is needed to diagnose and manage CAS. Whereas avoidance of cold exposure is the primary therapy, but no critical patient should be denied blood transfusion due to serological complications. All transfusion services should follow the correct protocol to maximize blood safety in CAS.

Assessment of spontaneous pneumothorax in adults in a tertiary care hospital.

CONTEXT: Pneumothorax continues to be a major cause of morbidity and mortality among respiratory patients, but there is a paucity of data regarding etiology, clinical profile, management, and outcome of spontaneous pneumothorax (SP), from this part of the world. AIMS: To assess the patients of spontaneous pneumothorax in adults with special reference to the etiology, clinical presentation, management, and outcome of SP. SETTINGS AND DESIGN: Prospective, observational study conducted in a tertiary care institution over a period of one year. MATERIALS AND METHODS: All adult patients of SP attending the department of pulmonary medicine in a tertiary hospital were studied and detailed clinical, radiological, and management data were recorded and analyzed. RESULTS: Sixty consecutive patients, who satisfied the inclusion criteria were included in the study. Among them 10 had primary spontaneous pneumothorax (PSP) and 50 had secondary spontaneous pneumothorax (SSP). The overall male to female ratio was 4:1. The mean age of the PSP patients was 26.3 ± 2.19 years, whereas, that of the SSP patients was 53.42 ± 2.07 years (P < 0.0001). Seventy percent of the patients were smokers. The most common clinical manifestation of PSP was chest pain (80%) in contrast to dyspnea in SSP (96%). The most common cause of SSP (42%) was found to be chronic obstructive pulmonary disease (COPD) followed by pulmonary tuberculosis (30%). The cases were managed with intercostal tube drainage (85%), simple aspiration (8.33%), and observation (6.67%). Full expansion of the lung was noted in 91.67% of the cases. CONCLUSION: Spontaneous pneumothorax was more common in men. SSP was far more common in this study, and the predominant underlying cause of SSP was COPD, which surpassed tuberculosis as the leading cause of SSP. This is in contrast to the results from previous studies done in our country. Intercostal tube drainage was the mainstay of treatment and the response was good.

Anomalously augmented charge transport capabilities of biomimetically transformed collagen intercalated nanographene-based biocolloids.

Collagen microfibrils biomimetically intercalate graphitic structures in aqueous media to form graphene nanoplatelet-collagen complexes (G-Cl). Synthesized G-Cl-based stable, aqueous bionanocolloids exhibit anomalously augmented charge transportation capabilities oversimple collagen or graphene based colloids. The concentration tunable electrical transport properties of synthesized aqueous G-Cl bionanocolloids has been experimentally observed, theoretically analyzed, and mathematically modeled. A comprehensive approach to mathematically predict the electrical transport properties of simple graphene and collagen based colloids has been presented. A theoretical formulation to explain the augmented transport characteristics of the G-Cl bionanocolloids based on the physicochemical interactions among the two entities, as revealed from extensive characterizations of the G-Cl biocomplex, has also been proposed. Physical interactions between the zwitterionic amino acid molecules within the collagen triple helix with the polar water molecules and the delocalized π electrons of graphene and subsequent formation of partially charged entities has been found to be the crux mechanism behind the augmented transport phenomena. The analysis has been observed to accurately predict the degree of enhancement in transport of the concentration tunable composite colloids over the base colloids. The electrically active G-Cl bionanocolloids with concentration tunability promises find dual utility in novel gel bioelectrophoresis-based protein separation techniques and advanced surface charge modulated drug delivery using biocolloids.

Contralateral contiguous tuberculous lymphadenitis in a case of right breast carcinoma--Diagnostic dilemma.

Coexistence of tuberculosis (TB) in the breast or axillary lymph nodes with breast carcinoma though rare is not unknown. A 55-year-old woman presented with right axillary and left supraclavicular lymphadenopathies with no detectable lesion in either breasts or left axilla. Right axillary lymph node excision biopsy revealed metastatic adenocarcinoma. Diagnostic workup showed intense fluorodeoxyglucose (FDG)-avid lymph nodes on the left side neck at level V, supraclavicular, axillary, subpectoral and para-aortic regions, and low FDG activity in the right breast. Core biopsy of right breast lesion was reported as invasive ductal carcinoma and cytology of multiple left axillary lymphadenopathies as reactive hyperplasia. Excision biopsy of the supraclavicular lymph nodes unveiled the diagnosis of TB. She underwent right-modified radical mastectomy followed by external beam radiotherapy, has completed antituberculous treatment and is on follow-up. Extrapulmonary TB though uncommon; may be found in certain cases. Clinicians must be aware of its existence.

Cervical lymphadenopathy--pitfalls of blind antitubercular treatment.

Tuberculosis (TB) is the most common cause of cervical lymphadenopathy in the TB-endemic zone, like India but it can also mimic other diseases. Four cases of cervical lymphadenopathy presented to us as initial treatment failure after completion of six months of antitubercular drugs (ATD), including rifampicin, isoniazid, pyrazinamide, and ethambutol. All were diagnosed as having tuberculosis either by fine needle aspiration cytology or clinically from outside our institution. In one case, tuberculosis was the final diagnosis but, unfortunately, it was multidrug-resistant. In other three cases, Hodgkin disease, Non-Hodgkin lymphoma, and Kikuchi's disease were the diagnoses. In resource-poor countries, like India, which is also a TB-endemic zone, TB should be the first diagnosis in all cases of chronic cervical lymphadenopathy, based on clinical and/or cytological evidences. So, they were correctly advised antitubercular therapy (ATT) initially. Sometimes, TB mimics other aetiologies where apparent initial improvement with ATT finally results in treatment failure. Hence, investigations for microbiological and histopathological diagnosis are warranted, depending on the resources and feasibility. If these tests are not routinely available, the patients should be under close monitoring so that lymphoma, drug-resistant TB, or other aetiologies of cervical lymphadenopathy are not missed. Patients with cervical lymphadenopathy rarely presents acutely; so, a physician can take the opportunity of histopathological study of lymphnode tissue.

Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity.

In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed "biomimetic". Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells.

Controlling ferrofluid permeability across the blood­brain barrier model.

In the present study, an in vitro blood­brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood­brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood­brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood­brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood­brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood­brain barrier (e.g. CPB).

Managing uncontrolled postsplenectomy reactive thrombocytosis in idiopathic thrombocytopenic purpura: role of thrombocytapheresis.

Reactive thrombocytosis occurs in response to infection, trauma, or surgery. Splenectomy alone accounts for 19% of all possible causes of extreme thrombocytosis. We performed thrombocytapheresis in a young lady with chronic idiopathic thrombocytopenic purpura (ITP) who developed postsplenectomy reactive thrombocytosis. Her post splenectomy platelet count was 227 × 10(6)/ml which elevated to 1623 × 10(6)/ml on the 7th postoperative day. A single thrombocytapheresis procedure reduced her platelet to 403 × 10(6)/ml. She was discharged on the 10th postoperative day and then maintained a count of 204-238 × 10(6)/ml with aspirin. Thrombocytapheresis reduces the platelet count rapidly in thrombocytosis and prevents patients from having thrombotic events. However, such procedures should be performed very meticulously to ensure patient safety.

Comparison study of ferrofluid and powder iron oxide nanoparticle permeability across the blood-brain barrier.

In the present study, the permeability of 11 different iron oxide nanoparticle (IONP) samples (eight fluids and three powders) was determined using an in vitro blood-brain barrier model. Importantly, the results showed that the ferrofluid formulations were statistically more permeable than the IONP powder formulations at the blood-brain barrier, suggesting a role for the presently studied in situ synthesized ferrofluid formulations using poly(vinyl) alcohol, bovine serum albumin, collagen, glutamic acid, graphene, and their combinations as materials which can cross the blood-brain barrier to deliver drugs or have other neurological therapeutic efficacy. Conversely, the results showed the least permeability across the blood-brain barrier for the IONP with collagen formulation, suggesting a role as a magnetic resonance imaging contrast agent but limiting IONP passage across the blood-brain barrier. Further analysis of the data yielded several trends of note, with little correlation between permeability and fluid zeta potential, but a larger correlation between permeability and fluid particle size (with the smaller particle sizes having larger permeability). Such results lay the foundation for simple modification of iron oxide nanoparticle formulations to either promote or inhibit passage across the blood-brain barrier, and deserve further investigation for a wide range of applications.

A rare mediastinal tumour in a young male mimicking massive pleural effusion.

A 30-year-old male, carpenter by profession, presented with a history of dry cough and progressive shortness of breath for two months along with right-sided chest pain for one and a half months. The clinico-radiological picture was suggestive of right-sided massive pleural effusion. Computed tomography (CT) scan of the thorax showed a huge mediastinal mass occupying the entire right hemithorax with very small amount of pleural effusion. CT-guided fine needle aspiration cytology and tru-cut biopsy from the mass both revealed small round-cell tumour, possibly small cell carcinoma of the lung. However, on immunohistochemistry tumour cells expressed Mic-2 and it was consistent with a diagnosis of primitive neuroectodermal tumour.