The research group BioMaterial Engineering works towards development and production techniques for new electrode concepts for active implants. Our material concepts cover nanocomposites, microelectronic circuits for implantable on-board electronics in ECoGs as well as encapsulation strategies for chronic ECoG application. Silicone rubber 3D printing is developed for medical device applications. We develop biochemical sensors for acute in-vivo use as well actuators that allow implants to wrap around their target tissue.
The work group has a dual appointment to High-Performance Center Medical and Pharmaceutical Engineering at Fraunhofer ITEM. In this context we also perform biocompatibilty tests as well as tests and documentation according to DIN/ISO 13485.
Implantation of medical devices is commonly accompanied by inflammatory reactions. The possibility to detect such an inflammation as soon as possible leads to the idea of a biodegradable inflammation sensor on Cochlear Implants. This is realized using a layer of Molecularly Imprinted Polymers (MIPs) to detect inflammation markers using the impedance changes on CI electrode contacts. The biodegradable MIPs layer will be reduced over a period of time to reveal the electrode contacts for regular stimulation. Measurement of inflammation markers will allow physicians to medicate the patient according to the severity of inflammation.
3D printing is omnipresent in research nowadays. Since silicone rubber is a commonly used material in medical implants, a 3D-printer for medical grade silicone rubber was developed in this work group. Printing of medical grade silicone rubber as well as conductive pathways for (active) implants is possible using laser accelerated curing.
The 3D printer functions are augmented towards a hybrid manufacturing platform. A pick-and-place-system is integrated to allow a simultaneous printing of electrodes and insertion of electronic components such as amplifiers or microcontrollers.
Cochlear Implants are constantly improved to reduce insertion trauma and allow for optimal hearing sensation. One improvement is a pre curved electrode shaft. We developed an actuator based on a hydrogel and silicone rubber compound to bend cochlear implants after implantation and allow for a patient-individual CI curvature depending on the amount of hydrogel in the compound.
All materials under investigation in our implant development research are under investigation for biocompatibility under ISO 10993. Cell proliferation and morphology as well as metabolism and toxicology are investigated parallel to material evaluation.
Materials used in implanted devices are under a lot of mechanical and chemical and, if applicable, electrical stress. The duration that materials can endure the harsh environment of the human body combined with the strain from their function is investigated both experimentally and in a numerical model. The resulting verified damage model can be used to reduce testing in future medical implant development and therefore allow for reduced costs.
Publications:
J. Stieghorst, K. Tegtmeier, P. Aliuos, H. Zernetsch, B. Glasmacher, T. Doll, Self-bending hydrogel actuation for electrode shafts in cochlear implants, 2014, PSSA DOI 10.1002/pssa.201330404.
K. Tegtmeier, P. Aliuos, J. Stieghorst, M. Schickedanz, H. Zernetsch, G. Glasmacher, T. Doll, Aligned carbon nanotube - liquid silicone rubber conductors and electrode surfaces for stimulating medical implants, 2015, PSSA DOI 10.1002/pssa.201330405.
J. Stieghorst, A. Bondarenkova, N. Burblies, P. Behrens, T. Doll, 3D silicone rubber interfaces for individually tailored implants, Biomedical Microdevices, 2015, DOI: 10.1007/s10544-015-9960-y.
K. Tegtmeier, P. Aliuos, T. Lenarz, T. Doll, Residual Rubber Shielded Multi Walled Carbon Nanotube Electrodes for Neural Interfacing in Active Medical Implants, Physics in Medicine, 2016, DOI: 10.1016/j.phmed.2016.04.001.
J. Stieghorst, B.N. Tran, S. Hadeler, D. Beckmann and T. Doll, Hydrogel-based actuation for modiolar hugging cochlear implant electrode arrays. Proc. Eng. 168, 1529-1532 (2016).
K. Tegtmeier, F. Borrmann and T. Doll, Wet-etch induced changes in impedance of carbon nanotube-silicone rubber electrode materials for active implants, Procedia Engineering; 2016, DOI: 10.1016/j.proeng.2016.11.393.
K. Hackner,P. Errhalt, M.R. Müller, M. Speiser, B. Marzluf, A. Schulheim, P. Schenk, J. Bilek, T. Doll, Canine scent detection for the diagnosis of lung cancer in a screening-like situation, J. Breath Res. 10 (2016) 046003 doi:10.1088/1752-7155/10/4/046003.
8. Stieghorst J, Majaura D, Wevering H, Doll T, Toward 3D printing of medical implants: Reduced lateral droplet spreading of silicone rubber under intense IR curing, ACS Appl. Mater. Interfaces 2016 Mar;8(12):8239-46. doi: 10.1021/acsami.5b12728
K. Hackner,P. Errhalt, T. Doll, Reply to Comment on 'Canine scent detection for the diagnosis of lung cancer in a screening-like situation', J. Breath Res. 11 038002 (2017) doi.org/10.1088/1752-7163/aa78fd
A. Behrens, K. Tegtmeier, T. Doll, Carbon Nanotube-Silicone Rubber Electrodes for Active Implants, PSSA 2017 accepted.
J. P. Marcoleta, W. Nogueira, U. Froriep, T. Doll, Flexible and High Density Active Neural Implants combining a Distributed Multiplexing Transceiver Architecture in Biocompatible Technology, Physica Status Solidi (a) Applications and Materials Science 215 (2018), No. 15, p. 1700134.doi: 10.1002/pssa.201700134
J. Stieghorst T. Doll, Rheological Behavior of PDMS Silicone Rubber for 3D Printing of Medical Implants, Additive Manufacturing, in press Oct. 4, 2018.
M. Pereira Madureira, J. P. Marcoleta, J. Stieghorst, S. Gassman, T. Doll, 3D printing of active medical implants, Trans. AMMM Vol 1 No 1 (2019) DOI 10.18416/AMMM.2019.1909S03P08.
J.P. Marcoleta; W. Nogueira; N. Becerra Yoma; J. Wuth; F. Jakimovski; V.M. Fuenzalida; T. Doll, Implantable Neuroamplifiers for Electrocorticography Using Flexible and Biocompatible Technology, Physica Status Solidi (A) - Applications and Materials Science, DOI: 10.1002/pssa.201900830.
G. Wackers, T. Putzeys, M. Peeters, L. Van de Cauter, P. Cornelis, M. Wübbenhorst, J. Tack, F. Troost, N. Verhaert, T. Doll, P. Wagner, Towards a catheter-based impedimetric sensor for the assessment of intestinal histamine levels in IBS patients, Biosensors and Bioelectronics, doi.org/10.1016/j.bios.2020.112152
J.P. Marcoleta, W. Nogueira, T. Doll, Distributed mixed signal demultiplexer for electrocorticography electrodes, 2020, Biomedical Physics & Engineering Express 2057-1976, N2 (accepted manuscript iopscience.iop.org/article/10.1088/2057-1976/ab9fed).
F.C. Wiegandt, U.P. Froriep, T. Doll, A. Dietzel, G. Pohlmann, Novel Test Bench for Inhaler Characterization Including Real-Time Determination of Output, Output Rate, and Liquid Water Content of Delivered Aerosols, Journal of Aerosol Medicine and Pulmonary Drug Delivery July 22, 2020 doi.org/10.1089/jamp.2020.1611
G. Wackers, P. Cornelis, T. Putzeys, M. Peeters, J. Tack, F. Troost, T. Doll, N. Verhaert and P. Wagner, Electropolymerized Receptor Coatings for the Quantitative Detection of Histamine with a Catheter-Based, Diagnostic Sensor, ACS Sensors (online Dec. 4, 2020) https://dx.doi.org/10.1021/acssensors.0c01844
Ailke Behrens, Jan Stieghorst, Theodor Doll, Ulrich P. Froriep, " Laser-Facilitated Additive Manufacturing Enables Fabrication of Biocompatible Neural Devices," Sensors 2020, 20(22), 6614; https://doi.org/10.3390/s20226614
Foremny, K., Konerding, W. S., Behrens, A., Baumhoff, P., Froriep, U. P., Kral, A., Doll, T. (2021). Carbon nanotube-coated surface electrodes for cortical recordings In Vivo. Nanomaterials (Basel) 11: 1029. doi: 10.3390/nano1104102 - Open Access.
Wiegandt, F. C., Biegger, D., Fast, J. F., Matusiak, G., Mazela, J., Ortmaier, T., Doll, T., Dietzel, A., Bohnhorst, B., Pohlmann, G. (2021). "Detection of Breathing Movements of Preterm Neonates by Recording Their Abdominal Movements with a Time-of-Flight Camera." Pharmaceutics 13(5). doi: 10.3390/pharmaceutics13050721 - Open Access.
Wiegandt, F. C., Froriep, U. P., Müller, F., Doll, T., Dietzel, A., Pohlmann, G. (2021). "Breath-triggered drug release system for preterm neonates." Pharmaceutics 13(5). doi: 10.3390/pharmaceutics13050657 - Open Access.
Lennart Guntenhöner, Katharina Foremny, Jan Stieghorst, Michaela Kreienmeyer, Theodor Doll,
3D quantification of short vertical neurites in membrane pores and their differentiation from other cell parts, Physics in Medicine, Volume 12, 2021, 100040, ISSN 2352-4510, https://doi.org/10.1016/j.phmed.2021.100040.
Wagner, P., Doll, T., Schoening, M.J. (2020). Engineering of Functional Interfaces. PHYSICA STATUS SOLIDI A-APPLICATIONS AND MATERIALS SCIENCE, 217 (13), Art.No. ARTN 2000345. doi: 10.1002/pssa.202000345
Wagner, P., Keusgen, M., Doll, T., Wagner, T., Schoning, M.J. (2018). Editorial. PHYSICA STATUS SOLIDI A-APPLICATIONS AND MATERIALS SCIENCE, 215 (15), Art.No. ARTN 1800519. doi: 10.1002/pssa.201800519
Wagner, P., Lisdat, F., Doll, T., Wagner, T., Schoning, M.J. (2017). Engineering of Functional Interfaces Preface. Physica Status Solidi A, Applications and Materials Research, 214 (9), Art.No. 1770154.
Doll, T., Wagner, T., Wagner, P., Schoening, M.J. (2016). Engineering of Functional Interfaces 2016 Preface. Physica Status Solidi A, Applications and Materials Research, 213 (6), 1393-1394.
Wagner, T., Wagner, P.H., Doll, T., Schoening, M.J. (2015). Engineering of functional interfaces. Physica Status Solidi A, Applications and Materials Research, 212 (6), 1183-1183.
Wagner, P.H., Doll, T., Schoening, M.J. (2014). Engineering of Functional Interfaces Preface. Physica Status Solidi A, Applications and Materials Research, 211 (6), 1339-1339.
Wagner, P.H., Doll, T., Keusgen, M., Schoening, M.J. (2011). Engineering of Functional Interfaces Preface. Physica Status Solidi A, Applications and Materials Research, 208 (6), 1216-1216. Open Access.
Wagner, P., Keusgen, M., Doll, T., Wagner, T., Schöning, M.J. (2018). Editorial. Physica Status Solidi (A) Applications and Materials Science, 215 (15). doi: 10.1002/pssa.201800519
Doll, T., Wagner, P.H., Schoening, M.J. (2009). Papers presented at the workshop on Engineering of Functional Interfaces - EnFI 08 Julich (Solar Campus of the Aachen University of Applied Sciences), Germany, 12-13 June 2008 Preface. Physica Status Solidi A, Applications and Materials Research, 206 (3), 389-390.
Wagner, P., Doll, T., Schöning, M.J. (2010). Physica Status Solidi (A) Applications and Materials: preface. Physica Status Solidi (A) Applications and Materials Science, 207 (4), 777-779. doi: 10.1002/pssa.200983325
T. Doll, H. Boettner, J. Woellenstein, M. JAegle, M. Lehmann, Micro-srucuresd gas sensor with control of gas sensitivie properties by application of an electrical field
S. Maeder, T. Haas, U. Kunze, T. Doll, Ultrathin metal oxidation for vacuum monitoring device applications.
Doll, T., Oberröhrmann, J., Baum, S., Köhler, R., Schütte, H., Gassmann, S., et al. (2021). Probing Ionization Energies for Trace Gas Identification: The Micro Photo Electron Ionization Detector (PEID), Chem. Proc. 2021, 3, x. https://doi.org/10.3390/ CSAC2021-10431.
Mao Y, Pechenizkiy I, Stieglitz T, Doll T. Numerical Evaluation on Residual Thermal Stress-Induced Delamination at PDMS-Metal Interface of Neural Prostheses. Micromachines. 2021; 12(6):669. https://doi.org/10.3390/mi12060669
Onken A, Schütte H, Wulff A, Lenz-Strauch H, Kreienmeyer M, Hild S, Stieglitz T, Gassmann S, Lenarz T, Doll T. Predicting Corrosion Delamination Failure in Active Implantable Medical Devices: Analytical Model and Validation Strategy. Bioengineering. 2022; 9(1):10. https://doi.org/10.3390/bioengineering9010010
Foremny K, Nagels S, Kreienmeyer M, Doll T, Deferme W. Biocompatibility Testing of Liquid Metal as an Interconnection Material for Flexible Implant Technology. Nanomaterials. 2021; 11(12):3251. https://doi.org/10.3390/nano11123251
Ali Abdul Nabi Ali, Mesbah Alam, Simon Klein, Nicolai Behmann, Joachim K. Krauss, Theodor Doll, Holger Blume, Kerstin Schwabe, Predictive accuracy of CNN for cortical oscillatory activity in an acute rat model of parkinsonism, Neural Networks, 2021, , ISSN 0893-6080, https://doi.org/10.1016/j.neunet.2021.11.025.
Secretary's office
Nadja Hasselberg
(0)511 532 1549
hasselberg.nadja(at)mh-hannover.de
NIFE
Stadtfelddamm 34
30625 Hanover
Lecture:
Microplastic manufacturing technology at Leibniz Universität Hannover