Advanced control strategies for continuous capture of monoclonal antibodies based upon biolayer interferometry.

The semi and fully continuous production of monoclonal antibodies (mAbs) has been gaining traction as a lower cost, and efficient production of mAbs to broaden patient access. To be truly flexible and adaptive to process demands, the industry has lacked sufficient advanced control strategies. The variation of the upstream product concentration typically cannot be handled by the downstream capture step, which is configured for a constant feed concentration and fixed binding capacity. This inflexibility leads to losses of efficiency and product yield. This study shows that these challenges can be overcome by a novel advanced control strategy concept that includes dynamic control throughout a perfusion bioreactor, with cell retention by alternating tangential flow, integrated with simulated moving bed (SMB) multi-column chromatography. The automation workflow and advanced control strategy were implemented through the use of a visual programming development environment. This enabled dynamic flow control across the upstream and downstream process integrated with a dynamic column loading of the SMB. A sensor prototype, based on continuous biolayer interferometry measurements was applied to detect mAb breakthrough within the last column flow-through to manage column switching. This novel approach provided higher specificity and lower background signal compared to commonly used spectroscopy methods, resulting in an optimized resin utilization while simultaneously avoiding product loss. The dynamic loading was found to provide a twofold increase of the mAb concentration in the eluate compared to a conservative approach with a predefined recipe with similar impurity removal. This concept shows that advanced control strategies can lead to significant process efficiency and yield improvement.

Screen-Printed Structures from a Highly Conductive Mildly Oxidized Graphene Suspension for Flexible Electronics.

In this study, the screen-printed flexible humidity sensor and supercapacitor structures from a suspension of mildly oxidized graphene (MOG) was obtained. MOG suspension with a low atomic oxygen content (~20%) was synthesized by electrochemical exfoliation of natural graphite in an aqueous solution of ammonium sulfate. MOG films (average thickness 5 µm) with a surface resistance of 102-103 kΩ/sq were obtained by screen printing on a flexible substrate. The thermal reduction of MOG films at 200 °C reduced the surface resistance to 1.5 kΩ/sq. The laser reduction with a 474 nm and 200 mW solid-state laser reduced the surface resistance to ~0.065 kΩ/sq. Various structures were screen-printed on a flexible substrate for a variety of flexible electronics applications. The structures representing a flat supercapacitor had an average specific capacitance of ~6 µF/cm2. The tensile deformations occurring during bending reduced the capacitance by 40% at a bending radius of 2 mm. Humidity sensing structures with sensitivity of 9% were obtained.

Graphene-PEDOT: PSS Humidity Sensors for High Sensitive, Low-Cost, Highly-Reliable, Flexible, and Printed Electronics.

A comparison of the structure and sensitivity of humidity sensors prepared from graphene (G)-PEDOT: PSS (poly (3,4-ethylenedioxythiophene)) composite material on flexible and solid substrates is performed. Upon an increase in humidity, the G: PEDOT: PSS composite films ensure a response (a linear increase in resistance versus humidity) up to 220% without restrictions typical of sensors fabricated from PEDOT: PSS. It was found that the response of the examined sensors depends not only on the composition of the layer and on its thickness but, also, on the substrate used. The capability of flexible substrates to absorb the liquid component of the ink used to print the sensors markedly alters the structure of the film, making it more porous; as a result, the response to moisture increases. However, in the case of using paper, a hysteresis of resistance occurs during an increase or decrease of humidity; that hysteresis is associated with the capability of such substrates to absorb moisture and transfer it to the sensing layer of the sensor. A study of the properties of G: PEDOT: PSS films and test device structures under deformation showed that when the G: PEDOT: PSS films or structures are bent to a bending radius of 3 mm (1.5% strain), the properties of those films and structures remain unchanged. This result makes the composite humidity sensors based on G: PEDOT: PSS films promising devices for use in flexible and printed electronics.