scholarly journals A microfluidic approach to studying the injection flow of concentrated albumin solutions

2021 ◽  
Vol 3 (9) ◽  
Author(s):  
Alfredo Lanzaro

Abstract Subcutaneous injection by means of prefilled syringes allows patients to self-administrate high-concentration (100 g/L or more) protein-based drugs. Although the shear flow of concentrated globulins or monoclonal antibodies has been intensively studied and related to the injection force proper of SC processes, very small attention has been paid to the extensional behavior of this category of complex fluids. This work focuses on the flow of concentrated bovine serum albumin (BSA) solutions through a microfluidic “syringe-on-chip” contraction device which shares some similarities with the geometry of syringes used in SC self-injection. By comparing the velocity and pressure measurements in complex flow with rheometric shear measurements obtained by means of the “Rheo-chip” device, it is shown that the extensional viscosity plays an important role in the injection process of protinaceous drugs. Article Highlights A microfluidic “syringe on chip” device mimicking the injection flow of protinaceous drugs has been developed. The velocity field of concentrated BSA solutions through the “syringe on chip” is Newtonian-like. The extensional viscosity of concentrated protein solutions should also be considered when computing injection forces through needles.

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Vincent K. Shen ◽  
Jason K. Cheung ◽  
Jeffrey R. Errington ◽  
Thomas M. Truskett

Proteins aggregate and precipitate from high concentration solutions in a wide variety of problems of natural and technological interest. Consequently, there is a broad interest in developing new ways to model the thermodynamic and kinetic aspects of protein stability in these crowded cellular or solution environments. We use a coarse-grained modeling approach to study the effects of different crowding agents on the conformational equilibria of proteins and the thermodynamic phase behavior of their solutions. At low to moderate protein concentrations, we find that crowding species can either stabilize or destabilize the native state, depending on the strength of their attractive interaction with the proteins. At high protein concentrations, crowders tend to stabilize the native state due to excluded volume effects, irrespective of the strength of the crowder-protein attraction. Crowding agents reduce the tendency of protein solutions to undergo a liquid-liquid phase separation driven by strong protein-protein attractions. The aforementioned equilibrium trends represent, to our knowledge, the first simulation predictions for how the properties of crowding species impact the global thermodynamic stability of proteins and their solutions.


Author(s):  
Yi-Cheng Hsieh ◽  
Huinan Liang ◽  
Jeffrey D. Zahn

Microdialysis is a commonly used technique for separating small biomolecules within a complex biological mixture for continuous biochemical monitoring. Microdialysis is based upon controlling the mass transfer rate of small biomolecules diffusing across a semipermeable membrane into a dialysis fluid while excluding larger molecules such as proteins. These small molecules are subsequently sensed using a biosensor. Since many biosensors are extremely susceptible to fouling, their stability and lifetime can be extended if metabolites are filtered through a microdialysis membrane before the dialysis fluid is moved into the sensor. Dialysis is also used commonly in biological laboratories to desalt high ionic strength protein solutions. As biochemical analysis systems become more integrated for μTAS systems there is a need to automate this process. Thus, an on-chip dialysis system is useful for biochemical reaction engineering where very tight control of ionic conditions must be maintained for effective enzymatic activity. This work demonstrates the ability to integrate polymer microdialysis membranes with microfluidic systems. Microchannels are bonded with a regenerated cellulose membrane. After microchannels are produced using standard processing techniques, they are integrated with these membranes. The cellulose is activated in an oxygen plasma followed by a lamination bond to the microchannels at moderate pressure and elevated temperature. Devices were placed in a solution of rhodamine dye, and dialysis fluid was allowed to flow through the microchannels. The outlet dye concentration was measured by fluorescence intensity as a function of flow rate and follows analytically predicted results.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2260
Author(s):  
Anna Rył ◽  
Piotr Owczarz

Low-concentrated colloidal chitosan systems undergoing a thermally induced sol–gel phase transition are willingly studied due to their potential use as minimally invasive injectable scaffolds. Nevertheless, instrumental injectability tests to determine their clinical utility are rarely performed. The aim of this work was to analyze the flow phenomenon of thermosensitive chitosan systems with the addition of disodium β-glycerophosphate through hypodermic needles. Injectability tests were performed using a texture analyzer and hypodermic needles in the sizes 14G–25G. The rheological properties were determined by the flow curve, three-interval thixotropy test (3ITT), and Cox–Merz rule. It was found that reducing the needle diameter and increasing its length and the crosshead speed increased the injection forces. It was claimed that under the considered flow conditions, there was no need to take into account the viscoelastic properties of the medium, and the model used to predict the injection force, based solely on the shear-thinning nature of the experimental material, showed very good agreement with the experimental data in the shear rate range of 200–55,000 s−1. It was observed that the increase in the shear rate value led to macroscopic structural changes of the chitosan sol caused by the disentangling and ordering of the polysaccharide chains along the shear field.


Author(s):  
N. Cheng ◽  
A. M. Gronenborn ◽  
C. M. Clore ◽  
A. C. Steven

Human macrophage inflammatory protein 1β (hMIP-1β), also known as Act-2, is a small protein that belongs to an extensive class of chemotactic cytokines. The high resolution solution structure of hMIP-1β has recently been determined by multidimensional NMR spectroscopy, revealing a dimeric molecule of 2 x 8 kDa. The fold of the monomer is very similar to that of the related cytokine, interleukin-8, which was solved previously. However, the mode of association whereby two monomers form a dimer is quite different. To maintain a sufficiently high concentration of soluble protein for NMR studies, hMIP-1β was dissolved at a pH of 2.5. During solubility trials, it was noticed that the hMIP-1β-containing solutions became birefringent at higher pHs, suggesting the formation of ordered light-scattering structures. We have investigated this phenomenon by negative staining electron microscopy.hMIP-1β was obtained from an expression vector, extracted from inclusion bodies, and purified as described. Protein solutions at 0.7 mg/ml, 100 mM NaCl, 20mM Na citrate, pH2.3, were dialyzed against 20mM ionic strength buffers at pH 4.5, 5.0 and 5.5 (sodium citrate), and pH 6.0 and 7.0 (sodium phosphate) at 4°C. Samples were withdrawn at various time-points, applied to glow-discharged carbon films, stained briefly (5s) with uranyl acetate, and examined in a Philips EM400RT microscope.


2017 ◽  
Vol 7 (6) ◽  
pp. 2308-2312
Author(s):  
M. Elashmawy

Injection process into a confined cross flow is quite important for many applications including chemical engineering and water desalination technology. The aim of this study is to investigate the performance of the injection process into a confined cross-flow of a round pipe using a single piston injection pump. A computational fluid dynamics (CFD) analysis has been carried out to investigate the effect of the locations of the maximum velocity and minimum pressure on the confined cross-flow process. The jet trajectory is analyzed and related to the injection pump shaft angle of rotation during the injection duty cycle by focusing on the maximum instant injection flow of the piston action. Results indicate a low effect of the jet trajectory within the range related to the injection pump operational conditions. Constant cross-flow was used and injection flow is altered to vary the jet to line flow ratio (QR). The maximum jet trajectory exhibits low penetration inside the cross-flow. The results showed three regions of the flow ratio effect zones with different behaviors. Results also showed that getting closer to the injection port causes a significant decrease on the locations of the maximum velocity and minimum pressure.


2021 ◽  
Vol 333 ◽  
pp. 16001
Author(s):  
Akihisa Matsui ◽  
Naoya Ogiyama ◽  
Takumi Endo ◽  
Jun Arakawa ◽  
Takao Nakagaki

Reduction of the energy penalty and cost of CO2 capture from concentrated gas streams using amine-based solutions can be achieved by minimizing the energy penalty in the solvent regeneration process. High concentration 2-Amino-2-methyl-1-propanol (AMP) solution precipitates as a carbonate when enough CO2 has been absorbed. By sending the separated carbonate to the stripper, the sensible heat of regeneration can be reduced. However, previous testing using 50 weight percent AMP solution mixed with Piperazine (PZ) with solid-liquid separation showed that the CO2 recovery rate was limited to 65% due to the lack of PZ regeneration. To improve the CO2 recovery rate, a novel solution and injection process were developed. N-Methyl-1,3-diaminopropane (MAPA) was selected as an alternative promoter based on reaction rate testing. Various tests were employed to characterize the behaviour of the AMP/MAPA solution under CO2 capture and recovery conditions. The injection point was relocated to avoid the inhibition of CO2 absorption observed when CO2 semi-lean liquid was sent to the upper portion of the absorber. The CO2 recovery rate and the precipitation quantity were simulated using a model built in Aspen Plus®. The novel solution and injection set-up were evaluated experimentally by a bench-scale apparatus.


2015 ◽  
Vol 493 (1-2) ◽  
pp. 70-74 ◽  
Author(s):  
Ingo Fischer ◽  
Astrid Schmidt ◽  
Andrew Bryant ◽  
Ahmed Besheer

2014 ◽  
Vol 889-890 ◽  
pp. 1638-1643
Author(s):  
Yi Zhang ◽  
Tong Tong Li ◽  
Yong Chen Song ◽  
Duo Li ◽  
Yang Chun Zhan ◽  
...  

The sensitivity analysis of wellbore heat transfer during the CO2injection process is of vital importance to Carbon dioxide utilization and sequestration (CCUS). A numerical simulation method is developed to simulate the process of wellbore heat transfer during injecting carbon dioxide by amending the classical heat transfer modelRamey models. It analyses how the selected parameters affect the distribution of the wellbore temperature and pressure, which include CO2injection temperature, pressure and density, the injection flow rate and Joule Thomson coefficient. The results show that, CO2injection temperature has greater impact on the initial level of the temperature distribution; higher injection pressure raises the temperature mainly because of the effect of Joule Thomson coefficient; also, when the injection process lasts a longer time, the distribution is much more stable. When the injection flow rate is higher, the strata temperature has less influence on the flow temperature. The injection pressure and density has very appreciable effect on the pressure distribution. However, the other parameters have less influence on it. The modified simulation method was applied in Jiangsu Caoshe oil field and the simulation results coincided with the measuring data well.


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