Arto Heiskanen

Technical University of Denmark | DTU · Department of BIOTECHNOLOGY AND BIOMEDICINE

Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better underst...

Bioimpedance and Bioelectricity Basics, Fourth Edition discusses, in detail, dielectric and electrochemical aspects, as well as electrical engineering concepts of network theory. The book takes readers from an introductory (postgraduate) level to a developed understanding of core dielectric and electrochemical aspects of bioelectricity combined wit...

The pathophysiological progress of Parkinson’s disease leads through degeneration of dopaminergic neurons in the substantia nigra to complete cell death and lack of dopamine in the striatum where it modulates motor functions. Transplantation of dopaminergic stem cell-derived neurons is a possible therapy to restore dopamine levels. We have previous...

Embedded 3D Printing In article number 2201392, Janko Kajtez, Jenny Emnéus, and co‐workers present a modular platform for bioengineering of neuronal networks via direct embedded 3D printing of human stem cells inside self‐healing annealable particle‐extracellular matrix (SHAPE) composites. The approach allows direct freeform patterning and function...

Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support f...

We present here the first impedance-based characterization of the differentiation process of two human mesencephalic fetal neural stem lines. The two dopaminergic neural stem cell lines used in this study, Lund human mesencephalic (LUHMES) and human ventral mesencephalic (hVM1 Bcl-XL), have been developed for the study of Parkinsonian pathogenesis...

Human in vitro models of neural tissue with controllable cellular composition, tunable microenvironment, and defined spatial patterning are needed to facilitate studies of brain development and disease. Towards this end, bioprinting has emerged as a promising strategy. However, precise and programmable printing of extremely soft and compliant mater...

3D interdigitated pyrolytic carbon microelectrodes (3D IDE) with high complexity and interconnectivity were fabricated taking advantage of suspended interdigitated microstructures. A novel fabrication method for a 3D interdigitated polymer precursor template was developed based on a dual photoresist process including multiple UV exposures at two di...

Brain organoids are considered to be a highly promising in vitro model for the study of the human brain and, despite their various shortcomings, have already been used widely in neurobiological studies. Especially for drug screening applications, a highly reproducible protocol with simple tissue culture steps and consistent output, is required. Her...

Carbon microelectrodes are being used extensively in numerous applications due to their intriguing and promising material properties. Here, we present the optimized fabrication of carbon nanograss (CNG) electrodes with a single-step UV lithography with SU-8 photoresist followed by maskless reactive-ion etching and pyrolysis. This simple method prov...

Hydrogels, biocompatible and hydrophilic polymeric networks, have been widely applied in, e.g., pharmaceutical and biomedical research. Their physico-chemical properties can be fine-tuned by changing the fraction and molecular structure of cross-linkers. Hydrogel layers with varying thickness have also been used to support biomimetic lipid bilayers...

A photoresponsive molecular-gated drug delivery system (DDS) based on silicone-hydrogel (poly(HEMA-co-PEGMEA)) interpenetrating polymer networks (IPNs) functionalized with carboxylated spiropyran (SPCOOH) was designed and demonstrated as an on-demand DDS. The triggered-release mechanism relies on controlling the wetting behavior of the surface by l...

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as host polymer and spiropyran (SP) functionalized guest polymer designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as it exploits the change in intermolecular inte...

Advancements in research on the interaction of human neural stem cells (hNSCs) with nanotopographies and biomaterials are enhancing the ability to influence cell migration, proliferation, gene expression, and tailored differentiation toward desired phenotypes. Here, the fabrication of pyrolytic carbon nanograss (CNG) nanotopographies is reported an...

In article number 2001150, Janko Kajtez, Johan Ulrik Lind, and co‐workers present a 3D printing approach to soft lithography for the manufacturing of open‐well compartmentalized microfluidic devices used to engineer human stem‐cell derived neural networks in vitro. The approach provides larger freedom of design, removes the need for manual postproc...

Christin Schuelke Poster FENS 2020

Compartmentalized microfluidic platforms are an invaluable tool in neuroscience research. However, harnessing the full potential of this technology remains hindered by the lack of a simple fabrication approach for the creation of intricate device architectures with high‐aspect ratio features. Here, a hybrid additive manufacturing approach is presen...

Evaluation and understanding the effect of drug delivery in in vitro systems is fundamental in drug discovery. We present an assay based on real-time electrical impedance spectroscopy (EIS) measurements that can be used to follow the internalisation and cytotoxic effect of a matrix metalloproteinase (MMP)–sensitive liposome formulation loaded with...

The transwell assay is currently the most popular approach to studying cellular invasion due to its ease of use and readout, and the possibility for quantitative measurements. However, it only allows end-point measurements without the possibility for real-time tracking of the dynamics of cell movement during an invasion. Moreover, it requires cell...

Vesicles constructed of either synthetic polymers alone (polymersomes) or a combination of polymers and lipids (lipo-polymersomes) demonstrate excellent long-term stability and ability to integrate membrane proteins. Applications using lipo-polymersomes with integrated membrane proteins require suitable supports to maintain protein functionality. U...

Over the past 30 years, stem cell technologies matured from an attractive option to investigate neurodegenerative diseases to a possible paradigm shift in their treatment through the development of cell-based regenerative medicine (CRM). Implantable cell replacement therapies promise to completely restore function of neural structures possibly chan...

In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic...

Harvesting the energy generated by photosynthetic organisms through light-dependent reactions is a significant step towards a sustainable future energy supply. Thylakoid membranes are the site of photosynthesis, and thus particularly suited for developing photo-bioelectrochemical cells. Novel electrode materials and geometries could potentially imp...

In this work, a poly (methyl methacrylate) membrane containing micro-holes (MHs) as a prototype of a simple sensing platform of a lab-on-a-chip device has been developed for a potential analysis of clinical fluidic samples. A four probe electrochemical impedance spectroscopy (EIS) setup, with two electrodes placed on each side of the membrane, was...

In this work, we present a dual-functional sensor that can perform surface-enhanced Raman spectroscopy (SERS) based identification and electrochemical (EC) quantification of analytes in liquid samples. A lithography-free reactive ion etching process was utilized to obtain nanostructures of high aspect ratios distributed homogeneously on a 4-inch fu...

The barley aleurone layer is an established model system for studying phytohormone signalling, enzyme secretion and programmed cell death during seed germination. Most analyses performed on the aleurone layer are end-point assays based on cell extracts, meaning each sample is only analysed at a single time point. By immobilising barley aleurone lay...

We present a robust easy to use lab-on-a-disc (LoD) device with integrated sample pre-treatment and electrochemical detection system for cell-free detection of a secondary metabolite, p-Coumaric acid (pHCA), produced by genetically modified E. coli. In the LoD device, which incorporates eight filtration and electrochemical detection units, the samp...

In this study, we explore the potential of electrical impedance tomography (EIT) for miniaturised 3D samples to provide a noninvasive approach for future applications in tissue engineering and 3D cell culturing. We evaluated two different electrode configurations using an array of nine circular chambers (Ø 10 mm), each having eight gold plated need...

We compare ultrasonic welding (UW) and thermal bonding (TB) for the integration of embedded thin-film gold electrodes for electrochemical applications in injection molded (IM) microfluidic chips. The UW bonded chips showed a significantly superior electrochemical performance compared to the ones obtained using TB. Parameters such as metal thickness...

An impedance-based label-free affinity sensor was developed for the recognition of glycated hemoglobin (HbA1c). Interdigitated gold microelectrode arrays (IDA) were first modified with a self-assembled monolayer of cysteamine followed by cross-linking with glutaraldehyde and subsequent binding of 3-aminophenylboronic acid (APBA), which selectively...

Redox regulation is important for numerous processes in plant cells including abiotic stress, pathogen defence, tissue development, seed germination and programmed cell death. However, there are few methods allowing redox homeostasis to be addressed in whole plant cells, providing insight into the intact in vivo environment. An electrochemical redo...

This work presents the fabrication and characterization of suspended three-dimensional (3D) pyrolytic carbon microelectrodes for electrochemical applications. For this purpose, an optimized process with multiple steps of UV photolithography with the negative tone photoresist SU-8 followed by pyrolysis at 900ºC for 1h was developed. With this proces...

This work presents the fabrication and characterization of multi-layered three-dimensional (3D) pyrolysed carbon microelectrodes for electrochemical applications. For this purpose, an optimized UV photolithography and pyrolysis process with the negative tone photoresist SU-8 has been developed. The fabricated three electrode electrochemical cell is...

Parkinson’s disease is a serious problem, especially as the life span increases in the general population, mostly because there is no cure and the current treatment options are far from being optimal. The disease is characterized by insufficient dopamine in the brain, a neurotransmitter involved in the motor function. Recent approaches recognize th...

Limitations in controlling scaffold architecture using traditional fabrication techniques are a problem when constructing engineered tissues/organs. Recently, integration of two pore architectures to generate dual-pore scaffolds with tailored physical properties has attracted wide attention in tissue engineering community. Such scaffolds features p...

In this study, we perform experimental studies as well as simulations for cyclic voltammetry(CV) of the redox couple FeIII(CN)63-/FeII(CN)64- on a gold plated ECC biosensor encapsulated by a microfluidic system. We examine the effect of flow rate, scan rate, varying supporting electrolyte, exchange current density and the position of electrode on t...

Study of the copper binding properties of metformin is important for revealing its mechanism of action as a first-line type-2 diabetes drug. A quantitative investigation of interactions between metformin and l-cysteine-copper complexes was performed. The results suggest that metformin could interact with biological copper, which plays a key role in...

Impedance is a promising technique for sensing the overall process of tissue engineering. Different electrode configurations can be used to characterize the scaffold that supports cell organization in terms of hydrogel polymerization and degree of porosity, monitoring cell loading, cell proliferation as well as the spatial distribution of cell aggr...

We present the characterisation and validation of multiplexed 4-terminal (4T) impedance measurements as a method for sensing the spatial location of cell aggregates within large three-dimensional (3D) gelatin scaffolds. The measurements were performed using an array of four rectangular chambers, each having eight platinum needle electrodes for para...

We propose a novel alternative approach to long-term glycaemic monitoring using eggshell membranes (ESMs) as a new immobilising platform for the selective label-free electrochemical sensing of glycated haemoglobin (HbA1c), a vital clinical index of the glycaemic status in diabetic individuals. Due to the unique features of a novel 3-aminophenylboro...

We investigated the combined effect between the initial cell density (12500, 35000, 75000, and 100000 cell/cm2) and concentrations of the anti-cancer drug Doxorubicin on HeLa cells by performing time-dependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation between the rate of cell death and the initial cel...

In this work, we compare pyrolyzed carbon derived from the photoresist SU-8 alone or in combination with polystyrene and poly(styrene)-block-poly(dimethylsiloxane) copolymer (PS-b-PDMS), to be used as novel materials for micro- and nanoelectrodes. The pyrolyzed carbon films are evaluated with scanning electron microscopy, thermal gravimetric analys...

Black lipid membranes (BLMs) are significant in studies of membrane transport, incorporated proteins/ion transporters, and hence in construction of biosensor devices. Although BLMs provide an accepted mimic of cellular membranes, they are inherently fragile. Techniques are developed to stabilize them, such as hydrogel supports. In this paper, we pr...

As a part of developing new systems for continuously monitoring the presence of pesticides in groundwater, a microfluidic amperometric immunosensor was developed for detecting the herbicide residue 2,6-dichlorobenzamide (BAM) in water. A competitive immunosorbent assay served as the sensing mechanism and amperometry was applied for detection. Both...

We investigate the effect of flow rate on the electrical current response to the applied voltage in a micro electrochemical system. To accomplish this, we considered an ion-transport model that is governed by the Nernst-Planck equation coupled to the Navier-Stokes equations for hydrodynamics. The Butler-Volmer relation provides the boundary conditi...

In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anti-cancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, developed for targeted drug delivery, was evaluated using...

Down scaling of microfluidic cell culture and detection devices for electrochemical monitoring is mostly focused on the miniaturization of the microfluidic chips which are often designed for specific applications and therefore they lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with...

We present the application of electrochemical impedance spectroscopy (EIS) as a method for discriminating between different polydimethylsiloxane (PDMS) scaffolds for three-dimensional (3D) cell cultures. The validity of EIS characterisation for scaffolds having different degree of porosity (networks of structured or random channels) is discussed in...

Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3D-carbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed carbon material induces spontaneous hNSC differentiat...

We present the potential role of aptamers in elucidating the function of hypothetical proteins, as well as the possibilities provided by bioinformatics for establishing a benchmark for aptamer-protein prediction methods. With these future perspectives, the role of hypothetical proteins as target molecules for diagnostics and therapies could prove t...

In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes functioning as a counter and reference electrode in cl...

A theoretical and experimental comparison between vertical and coplanar interdigitated sensing configurations for impedimetric cell growth tracking is presented. These widely-adopted approaches are quantitatively compared on the same cell populations and on the same 10 μm interdigitated microelectrodes using a versatile custom-made monitoring platf...

A surface modification of interdigitated gold microelectrodes (IDEs) with a doped polypyrrole (PPy) film for detection of dopamine released from populations of differentiated PC12 cells is presented. A thin PPy layer was potentiostatically electropolymerized from an aqueous pyrrole solution onto electrode surfaces. The conducting polymer film was d...

In this work, we develop a generic DNA based sensing platform used for characterizing surface functionalization and detecting DNA hybridization. Silicon nitride cantilever sensors are fabricated with an integrated three-electrode system and integrated in a microfluidic chip. Cantilevers with gold electrodes are functionalized with thiol-modified si...

Conventionally, microbial bioelectrochemical assays have been conducted using immobilized cells on an electrode that is placed in an electrochemical batch cell. In this paper, we describe a developed microfluidic platform with integrated microelectrode arrays for automated bioelectrochemical assays utilizing a new double mediator system to map redo...

Since the use of impedance measurements for label-free monitoring of cells has become widespread but still the choice of sensing configuration is not unique though crucial for a quantitative interpretation of data, we demonstrate the application of a novel custom multipotentiostat platform to study optimal detection strategies. Electrochemical Impe...

A novel potentiostat containing 54 current amplifiers matched to an array of custom-fabricated 5μm microelectrodes for electrochemical imaging of released neurotransmitters is presented. The board is integrated with a programmable microfluidic cell culture system and the whole assembly is thin and compact enough to be placed under the objective of...

An electrochemical detection system specifically designed for multi-parameter real-time monitoring of stem cell culturing/differentiation in a microfluidic system is presented. It is composed of a very compact 24-channel electronic board, compatible with arrays of microelectrodes and coupled to a microfluidic cell culture system. A versatile data a...

SU-8 is the preferred photoresist for development and fabrication of high aspect ratio (HAR) three dimensional patterns. However, processing of SU-8 is a challenging task, especially when the film thickness as well as the aspect ratio is increasing and the size of the features is close to the resolution limit of photolithography. This paper describ...

Biosensing systems based on detecting changes in cantilever surface stress have attracted great interest. To achieve high reliability of measurements, high quality and high reproducibility in functionalization of the sensor surface are key points. In this paper, we investigate different methods to clean and regenerate the sensing surface of cantile...

The elucidation of the human and Saccharomyces cerevisiae genomes has opened new possibilities in biology, medicine and drug discovery. This knowledge has increased the number of targets and ways to treat diseases; clinical studies of disease manifestation can effectively be translated to the level of certain genes and their products, proteins. The...

A versatile microfluidic, multichamber cell culture and analysis system with an integrated electrode array and potentiostat suitable for electrochemical detection and microscopic imaging is presented in this paper. The system, which allows on-line electrode cleaning and modification, was developed for real-time monitoring of cellular dynamics, exem...