Edwin Jager

Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function

Significant advances have been made in the understanding of the pathophysiology, molecular targets and therapies for the treatment of a variety of nervous-system disorders. Particular therapies involve electrical sensing and stimulation of neural activity, and significant effort has therefore been devoted to the refinement of neural electrodes. However, direct electrical interfacing suffers from some inherent problems, such as the inability to discriminate amongst cell types. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmitters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmitters, the device mimics the nerve synapse. Using the peripheral auditory system, we show that out of a diverse population of cells, the device can selectively stimulate nerve cells responding to a specific neurotransmitter. This is achieved by precise electronic control of electrophoretic migration through a polymer film. This mechanism provides several sought-after features for regulation of cell signalling: exact dosage determination through electrochemical relationships, minimally disruptive delivery due to lack of fluid flow, and on-off switching. This technology has great potential as a therapeutic platform and could help accelerate the development of therapeutic strategies for nervous-system disorders.

Electrochemical modulation of epithelia formation using conducting polymers

Conducting polymers are soft, flexible materials, exhibiting material properties that can be reversibly changed by electrochemically altering the redox state. Surface chemistry is an important determinant for the molecular events of cell adhesion. Therefore, we analyzed whether the redox state of the conducting polymer PEDOT:Tosylate can be used to control epithelial cell adhesion and proliferation. A functionalized cell culture dish comprising two adjacent electrode surfaces was developed. Upon electronic addressing, reduced and oxidized surfaces are created within the same device. Simultaneous analysis of how a homogenous epithelial MDCK cell population responded to the electrodes revealed distinct surface-specific differences. Presentation of functional fibronectin on the reduced electrode promoted focal adhesion formation, involving alpha(v)beta(3) integrin, cell proliferation, and ensuing formation of polarized monolayers. In contrast, the oxidized surface harbored only few cells with deranged morphology showing no indication of proliferation. This stems from the altered fibronectin conformation, induced by the different surface chemistry of the PEDOT:Tosylate electrode in the oxidized state. Our results demonstrate a novel use of PEDOT:Tosylate as a cell-hosting material in multiple-electrode systems, where cell adhesion and proliferation can be controlled by electrochemical modulation of surface properties.

Control of neural stem cell adhesion and density by an electronic polymer surface switch.

Adhesion is an essential parameter for stem cells. It regulates the overall cell density along the carrying surface, which further dictates the differentiation scheme of stem cells toward a more matured and specified population as well as tissue. Electronic control of the seeding density of neural stem cells (c17.2) is here reported. Thin electrode films of poly(3,4-ethylenedioxythiophene) (PEDOT):Tosylate were manufactured along the floor of cell growth dishes. As the oxidation state of the conjugated polymer electrodes was controlled, the seeding density could be varied by a factor of 2. Along the oxidized PEDOT:Tosylate-electrodes, a relatively lower density of, and less tightly bonded, human serum albumin (HSA) was observed as compared to reduced electrodes. We found that this favors adhesion of the specific stem cells studied. Surface analysis experiments, such as photoelectron spectroscopy, and water contact angle measurements, were carried out to investigate the mechanisms responsible for the electronic control of the seeding density of the c17.2 neural stem cells. Further, our findings may provide an opening for electronic control of stem cell differentiation.

Polypyrrole micro actuators

The doping and undoping of conjugated polymers is accompanied by a volume change. This volume change can be used to make micro-actuators. We have built polypyrrole (PPy) gold bilayer structures. The volume change of PPy induces a bending of the bilayer. We have made micro-actuators based on this principle, which have been examined with video-microscopy. Some applications for these microactuators are proposed, including opening and closing boxes for cell biology and nanoliter chemistry and micro-robotics.

Active Control of Epithelial Cell‐Density Gradients Grown Along the Channel of an Organic Electrochemical Transistor

Complex patterning of the extracellular matrix, cells, and tissues under in situ electronic control is the aim of the technique presented here. The distribution of epithelial cells along the channel of an organic electrochemical transistor is shown to be actively controlled by the gate and drain voltages, as electrochemical gradients are formed along the transistor channel when the device is biased..

Electronic control of cell detachment using a self-doped conducting polymer.

An electronic detachment technology based on thin films of a poly(3,4-ethylene-dioxythiophene) derivative is evaluated for controlled release of human epithelial cells. When applying a potential of ...

The Cell Clinic: Closable Microvials for Single Cell Studies

We present the development of a cell clinic. This is a micromachined cavity, or microvial, that can be closed with a lid. The lid is activated by two polypyrrole/Au microactuators. Inside the microvials two Au electrodes have been placed in order to perform impedance studies on single or a small number of cells. We report on impedance measurements on Xenopus leavis melanophores. We could measure a change in the impedance upon cell spreading and identify intracellular events such as the aggregation of pigment granules. The electrical data is correlated to optical microscopy.

Label-free impedimetric biosensor for Salmonella Typhimurium detection based on poly [pyrrole-co-3-carboxyl-pyrrole] copolymer supported aptamer.

The Gram-negative bacterium, Salmonella Typhimurium (S. Typhimurium) is a food borne pathogen responsible for numerous hospitalisations and deaths all over the world. Conventional detection methods for pathogens are time consuming and labour-intensive. Hence, there is considerable interest in faster and simpler detection methods. Polypyrrole-based polymers, due to their intrinsic chemical and electrical properties, have been demonstrated to be valuable candidates for the fabrication of chemo/biosensors and functional surfaces. Similarly aptamers have been shown to be good alternatives to antibodies in the development of affinity biosensors. In this study, we report on the combination of poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and aptamer for the development of a label-less electrochemical biosensor suitable for the detection of S. Typhimurium. Impedimetric measurements were facilitated by the effect of the aptamer/target interaction on the intrinsic conjugation of the poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and subsequently on its electrical properties. The aptasensor detected S. Typhimurium in the concentration range 10(2)-10(8) CFU mL(-1) with high selectivity over other model pathogens and with a limit of quantification (LOQ) of 100 CFU mL(-1) and a limit of detection (LOD) of 3 CFU mL(-1). The suitability of the aptasensor for real sample detection was demonstrated via recovery studies performed in spiked apple juice samples. We envisage this to be a viable approach for the inexpensive and rapid detection of pathogens in food, and possibly in other environmental samples.

Control of Neural Stem Cell Survival by Electroactive Polymer Substrates

Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy), a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs). NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS), tosylate (TsO), perchlorate (ClO4) and chloride (Cl), showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS) but low on PPy containing TsO, ClO4 and Cl. On PPy(DBS), NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS) created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS) films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs.

Effect of the Electrolyte Concentration and Substrate on Conducting Polymer Actuators

The effect of the electrolyte concentration (NaCl aqueous electrolyte) on the dimensional variations of films of polypyrrole doped with dodecylbenzenesulfonate PPy(DBS) on Pt and Au wires was studied. Any parallel reaction that occurs during the redox polymeric reaction that drives the mechanical actuation, as detected from the coulovoltammetric responses, was avoided by using Pt wires as substrate and controlling the potential limits, thus significantly increasing the actuator lifetime. The NaCl concentration of the electrolyte, when studied by cyclic voltammetry or chronoamperometry, has a strong effect on the performance as well. A maximum expansion was achieved in 0.3 M aqueous solution. The consumed oxidation and reduction charges control the fully reversible dimensional variations: PPy(DBS) films are faradaic polymeric motors. Parallel to the faradaic exchange of the cations, osmotic, electrophoretic, and structural changes play an important role for the water exchange and volume change of PPy(DBS).