Sensitive optical detection of clinically relevant biomarkers in affordable microfluidic devices: Overcoming substrate diffusion limitations

One of the biggest challenges in miniaturization of optical immunoassays is the short light path distance of microchannels/microcapillaries. Protein biomarkers are often presented in circulating blood in the picomolar-femtomolar range, requiring exceptional levels of sensitivity that cannot be met with traditional chromogenic substrates and without sophisticated, bulky detection systems. This study discloses an effective strategy for increasing the sensitivity and shorten the total test time for sandwich ELISAs in microfluidic devices optically interrogated, based on enhancing enzymatic amplification. We found that activity of Horseradish Peroxidase (HRP) in mesofluidic systems is highly limited by diffusion, therefore increasing the concentration of enzymatic substrate in these systems does not translate into an enhancement in enzymatic conversation. The opposite happens in microfluidic systems due to short diffusion distances, however increased concentration of the second enzymatic substrate, hydrogen peroxide (H 2O 2), leads to enzyme inhibition as herein reported. Consequently, we found that the molar ratio of o-phenylenediamine (OPD) to hydrogen peroxide from commercially substrate formulations is not suitable for miniaturized systems. Sandwich ELISA quantitation of a cancer biomarker PSA and human cytokine IL-1β in fluoropolymer microfluidic strips revealed over one order of magnitude increase in sensitivity and 10-fold decrease in incubation time by simply changing the molar ratio of OPD:H 2O 2 from 1:3 to 1:1 and increasing OPD concentration from 1 to 4 mg/ml. This enhancement in enzymatic amplification offers finally the sensitivity required for optical interrogation of novel portable and affordable microfluidic devices with inexpensive and ubiquitous smartphones and flatbed scanners. </p

A Lab-in-a-briefcase for rapid prostate specific antigen (PSA) screening from whole blood

We present a new concept for rapid and fully portable Prostate Specific Antigen (PSA) measurement, termed “Lab-in-a-Briefcase”, which integrates an affordable microfluidic ELISA platform utilising a melt-extruded fluoropolymer Micro Capillary Film (MCF) containing 10 bore, 200 μm internal diameter capillaries, a disposable multi-syringe aspirator (MSA) plus a sample tray pre-loaded with all required immunoassay reagents, and a portable film scanner for colorimetric signal digital quantitation. Each MSA can perform 10 replicate microfluidic immunoassays on 8 samples, allowing 80measurements to be made in less than 15 minutes based on semi-automated operation and norequirement of additional fluid handling equipment. An assay was optimised for measurement of a clinically relevant range of PSA from 0.9 to 60.0 ng/ml in 15 minutes with CVs in the order of 5% based on intra-assay variability when read using a consumer flatbed film scanner. The PSA assay performance in the MSA remained robust in the presence of undiluted or 1:2 diluted human serum or whole blood, and the matrix effect could simply be overcome by extending sample incubation times. The PSA "Lab-in-a-briefcase" is particularly suited to a low-resource health setting where diagnostic labs and automated immunoassay systems are not accessible, by allowing PSA measurement outside the laboratory using affordable equipment

Algumas incursões sobre o significado de espaço público nos pensamentos de Hannah Arendt, Jürgen Habermas, Charles Taylor e Nelson Saldanha

Algumas incursões sobre o significado de espaço público nos pensamentos de Hannah Arendt, Jürgen Habermas, Charles Taylor e Nelson Saldanh

LP-based heuristic procedure for the optimal design of water using networks with multi-contaminants

This paper proposes a new strategy for the optimal design of water-using networks in industrial systems featuring possibly more than a single water source and multiple contaminants. The model formulation is supported on a superstructure that exploits reuse opportunities and gives rise to a non-convex nonlinear which often leads to local optimal solutions. To overcome this, the new approach generates multiple initialization points, one for each possible sequence of operations, where a particular starting point is obtained by the sequential solution of a small set of related linear programs. The best solution of the several non-linear problems that are solved is then assumed to be the global optimal solution. The results obtained for a set of case studies have shown that the best initialization point is often the global optimal solution and that the procedure as a whole is efficient in escaping local optima

impacts on the health and work of caregivers in Portugal

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Mixed-Integer Linear Programming Approach for Life-Cycle Carpet Profit

This paper proposes an mixed-integer linear programming (MILP) model to accurately represent a product life-cycle design considering profit maximization. The model that takes into account the effects on the demand lev-el and a measure of the customer utility considering recycled raw materials and prices of the traditional and modular products. Demand functions for traditional and modular products are considered. Given the presence of bilinear terms in the formulation (for example due to the multiplication of product price for the demand), the multi-parametric disaggregation technique is used to obtain a line-ar model. The developed model is applied to a company that produces tradition-al carpets and it wants to manufacture carpets based on a new modular design where recycled materials must be incorporated. The objective of the company is to maximize the total profit taking into account the design specifications and the selling prices for traditional and modular carpets. In addition, the amount of square meters of traditional carpets must be determined and the take-back rate must be considered. The practical behavior of the formulation is analyzed through computational experiments exploring the analyzed case-study.Sociedad Argentina de Informática e Investigación Operativ

Mixed-Integer Linear Programming Approach for Life-Cycle Carpet Profit

This paper proposes an mixed-integer linear programming (MILP) model to accurately represent a product life-cycle design considering profit maximization. The model that takes into account the effects on the demand lev-el and a measure of the customer utility considering recycled raw materials and prices of the traditional and modular products. Demand functions for traditional and modular products are considered. Given the presence of bilinear terms in the formulation (for example due to the multiplication of product price for the demand), the multi-parametric disaggregation technique is used to obtain a line-ar model. The developed model is applied to a company that produces tradition-al carpets and it wants to manufacture carpets based on a new modular design where recycled materials must be incorporated. The objective of the company is to maximize the total profit taking into account the design specifications and the selling prices for traditional and modular carpets. In addition, the amount of square meters of traditional carpets must be determined and the take-back rate must be considered. The practical behavior of the formulation is analyzed through computational experiments exploring the analyzed case-study.Sociedad Argentina de Informática e Investigación Operativ

Mixed-Integer Linear Programming Approach for Life-Cycle Carpet Profit

This paper proposes an mixed-integer linear programming (MILP) model to accurately represent a product life-cycle design considering profit maximization. The model that takes into account the effects on the demand lev-el and a measure of the customer utility considering recycled raw materials and prices of the traditional and modular products. Demand functions for traditional and modular products are considered. Given the presence of bilinear terms in the formulation (for example due to the multiplication of product price for the demand), the multi-parametric disaggregation technique is used to obtain a line-ar model. The developed model is applied to a company that produces tradition-al carpets and it wants to manufacture carpets based on a new modular design where recycled materials must be incorporated. The objective of the company is to maximize the total profit taking into account the design specifications and the selling prices for traditional and modular carpets. In addition, the amount of square meters of traditional carpets must be determined and the take-back rate must be considered. The practical behavior of the formulation is analyzed through computational experiments exploring the analyzed case-study.Sociedad Argentina de Informática e Investigación Operativ