Home Medicine Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs
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Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs

  • Robert Mau EMAIL logo , Paul Oldorf , Rigo Peters and Hermann Seitz
Published/Copyright: September 30, 2016
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Current Directions in Biomedical Engineering
From the journal Current Directions in Biomedical Engineering Volume 2 Issue 1

Abstract

Drug delivery systems (DDS) ensure that therapeutically effective drug concentrations are delivered locally to the target site. For that reason, it is common to coat implants with a degradable polymer which contains drugs. However, the use of polymers as a drug carrier has been associated with adverse side effects. For that reason, several technologies have been developed to design polymer-free DDS. In literature it has been shown that micro-sized reservoirs can be applied as drug reservoirs. Inkjet techniques are capable of depositing drugs into these reservoirs. In this study, two different geometries of micro-sized reservoirs have been laden with a drug (ASA) using a drop-on-demand inkjet printhead. Correlations between the characteristics of the drug solution, the operating parameters of the printhead and the geometric parameters of the reservoir are shown. It is indicated that wettability of the surface play a key role for drug deposition into micro-sized reservoirs.

Keywords: drop-on-demand; droplet deposition; drug reservoir; inkjet printing; polymer-free drug delivery system

1 Introduction

It is well known that medical implants cause a reaction of the organism. Drugs are used to influence the immune response. Drug delivery systems (DDS) ensure the delivery of therapeutically effective drug concentrations locally to the target site. They have been shown to be quite promising in facing the major drawbacks of common methods (tablets, intravenous injection) as for instance biodistribution and systemic toxicity [1]. For that reason a wide range of disciplines are concentrating on the development of DDS. The main field is the development of drug eluting cardiovascular stents [2]. But also the fields of glaucoma implants [3] and implants for the inner ear [4] provide wide applications for DDS.

It is common to coat the implants with a degradable polymer incorporated with drugs. The use of polymers as drug carriers is not indisputable. Adverse side effects, for example late stent thrombosis, have been associated with polymeric coatings [5]. In the aim to reduce the use of the carrier polymers there has so far been a lot of research work in the field of discrete drug reservoirs on implant surfaces [5]. Promising geometries of reservoirs for DDS, such as drug eluting stents, are presented in [6]. Hsiao et al. show, that micro-sized reservoirs could lead to a significantly increase of drug capacity with an acceptable marginal trade-off in key clinical attributes such as fatigue safety. In this context it was shown before, that inkjet technique can be a suitable tool, to deposit drugs in micro-sized reservoirs [7].

The presented research work identifies the crucial factors of influence while realizing a drug deposition in laser-drilled micro-sized reservoirs using a drop-on-demand inkjet printhead. The factors of influence are divided into characteristics of the drug solution, operating parameters of the printhead and geometric parameters of the reservoir.

2 Material and methods

2.1 Printhead parameters

For inkjet printing, the drugs which are to be deposited need to be dissolved in appropriate solvents. The printability of the dissolution is also a crucial factor. It is well known that the printability is especially dependent on the viscosity as well as on the surface tension of the fluid to be printed. For drug-loading of micro-reservoirs the evaporation speed also plays a key role. The solvent has to evaporate as fast as possible from the reservoir’s surface so that the next droplet can be placed in. Acetylsalicylic acid (ASA = 99%, Sigma-Aldrich Chemie GmbH, Munich, Germany) is used as a model drug. ASA can be dissolved in various solvents. On the one hand, there is a need of a high saturation limit to deposit a high quantity of drug per single droplet, but on the other hand, a high drug-concentration may affect the printability of the solution. In order to provide a test substance ASA was dissolved in EtOH (≥99,8%, Carl Roth GmbH + Co. KG, Karlsruhe, Germany) by 40 mg/ml. EtOH (ethanol) is well established as a solvent for drugs and is known for its high evaporation rate (compared to other common solvents such as DMSO). The influence of ASA on the critical parameters of viscosity and surface tension is investigated. Viscosity measurements are performed with a rheometer (Haake Mars 2, Thermo Fisher Scientific, Waltham, MA, USA), surface tension measurements are performed with the Pendant Drop Method (OCA 40 Micro, DataPhysics Instruments GmbH, Neuhausen, Germany).

In order to deposit drugs in micro-sized reservoirs on implant surfaces a micro-dispensing device (Nanoplotter 2.1, GeSiM Gesellschaft für Silizium-Mikrosysteme mbH, Großerkmannsdorf, Germany) is used. The printhead (PicoTip J, GeSiM) follows the piezoelectric drop-on-demand principle (DoD), i.e. a drop is released exactly when the piezo ceramic actuator is triggered. In order to realize a precise deposition in micro-sized reservoirs, the major requirement is a reproducible droplet formation, with a suitable volume and trajectory of the droplet. For that reason, the droplet formation of the test substance is investigated under the use of various drive parameters. The major parameters to control the droplet formation of piezo driven printheads are the voltage, pulse width and frequency as well as the nozzle diameter of the printhead. In this study, the printhead is driven with a voltage of 40 V up to 80 V (in 5 V steps). The pulse width (20 μs) and frequency (100 Hz) are set to fix standard values. With reference to the nozzle diameter of the printhead (d = 25 μm), droplets with ∼40 μm in diameter should be expected. The droplet formation is monitored by a stroboscope camera. The resulting image is analyzed with respect to the droplet volume and droplet positioning estimation. A deviation of the droplet trajectory from the vertical line is denoted as angle failure. Five droplets are analyzed per 5 V step using this method. The results will be compared to the printing process of pure EtOH.

2.2 Drug depositing into micro-sized reservoirs

In this study drug depositing is applied to two variants of reservoirs. Variant one has a diameter of ∼100 μm and a depth of ∼20 μm (R100-20); variant two has a higher depth of ∼50 μm (R100-50). The reservoir generation was performed by a picosecond laser (TruMicro 5 × 50, TRUMPF Laser- und Systemtechnik GmbH & Co.KG, Ditzingen, Germany) using a high-precision micromachining system (GL.5, GFH GmbH, Deggendorf, Germany). Picosecond laser provide a high peak power and extremely short interaction time. As result the reservoirs show a sharp contour (see Figure 1).

Figure 1 Confocal laser scanning microscopy (CLSM)-picture of a reservoir R100-50.
Figure 1

Confocal laser scanning microscopy (CLSM)-picture of a reservoir R100-50.

The micro dosing device uses automatic target recognition to identify the reservoirs. It is assumed that after being printed, the solvent will vaporize and there will be a deposit of drug in the reservoir. Approximately 2 ng of ASA is printed per droplet (∼50 pl). The volume of a reservoir is limited (R100-20 ∼120 pl; R100-50 ∼270 pl). In order to achieve a fill grade of ∼50%, 42 droplets have to be printed in a 100-20 reservoir (calculated with ρASA = 1,35 g/cm3). Because of the limited volume of the reservoirs, there is the need to split the depositing into steps, because the drug-solution needs time to vaporize and overfilling should be avoided. In a first test setup, a reservoir was filled with three droplets per step and 14 steps were performed, with a delay of ∼5 s each. However, such small amounts of fluid are subject to effects like wettability. For that reason two more test setups with a reduced number of droplets per step were performed. In the second test setup, a reservoir was filled with two droplets per step and 21 steps were performed. In the last (3rd) test setup, 42 steps were performed with 1 droplet each. The reservoirs R100-50 were laden with the same test setups. Five reservoirs were filled for each setup.

3 Results and discussion

3.1 Printhead parameters

As expected the droplet formation depends on the applied voltage pulses of the piezo. Increasing the voltage increases the droplet volume and decreases the angle failure (see Figures 2 and 3). If the printhead is driven at low voltage (40 V/45 V), a single droplet is formed with a low droplet volume (Figure 4A). However, there is a significant angle failure as a result of a low droplet speed that is caused by the low application of energy. At higher voltage, the main droplet is followed by a single satellite droplet. As seen in Figure 4B, the satellite is located in the trajectory of the main droplet. If the voltage is increased (70 V) the number of satellite droplets increases as well as the droplet volume. Furthermore, an upper limit of voltage was determined. If the piezo is driven with a voltage of about 75 up to 80 V, the reproducibility of the droplet formation decreases and a sort of spattering can be observed (Figure 4C). Under these conditions a measurement of droplet volume and angle failure was not possible. In comparison to inkjet printing of pure ethanol, ASA seemed to have no significant influence on the droplet formation. However there is a tendency to a lower angle failure. All in all, these results coincide with the expectations derived from surface tension measurements (EtOH: Ø22,5 mN/m, EtOH+ASA: Ø22,4 mN/m, n = 5) and viscosity measurements (EtOH: Ø1,18 mPas, EtOH+ASA: Ø1,23 mPas, n = 3, y˙ = 25/s, double-cone geometry 60/1°), where no significant influence of EtOH due to ASA was determined.

For a precise droplet deposition there is a need of a high reproducibility of droplet formation and a low angle failure. Because of that, a piezo driving voltage of 60 V was determined for the drug deposition in micro-sized reservoirs.

Figure 2 Droplet volume over driving voltage of the printhead.
Figure 2

Droplet volume over driving voltage of the printhead.

Figure 3 Angle failure of main droplet over driving voltage of the printhead.
Figure 3

Angle failure of main droplet over driving voltage of the printhead.

Figure 4 Droplet formation of EtOH+ASS under different voltage pulses (stroboscope delay 200 μs) (A) 40 V; (B) 60 V; (C) 80 V.
Figure 4

Droplet formation of EtOH+ASS under different voltage pulses (stroboscope delay 200 μs) (A) 40 V; (B) 60 V; (C) 80 V.

3.2 Drug depositing

Figure 5A shows the results of drug depositing in R100-20 by the first test setup. The drug is deposited around the reservoir, instead of inside the reservoir. For test setups no. 2 and 3, the effect decreases significantly. However, drug sedimentations around the reservoir cannot be eliminated (Figure 5B) for this reservoir size. The reason for this could be a wetting of the surface around the reservoir, possibly caused by an overfilling or missing of the reservoirs. In comparison to these results, filling deeper reservoirs (R100-50) results in deposits of the drug inside the reservoir (Figure 5C). This is an indication for valid droplet positioning. However, it can be seen that the deposit of ASA is concentrated at the walls of the reservoir.

Figure 5 Drug-laden reservoirs (A) R100-20 filled in 14 steps and 3 droplets/step; (B) R100-20 filled in 42 steps and 1 droplet/step; (C) R100-50 filled in 42 steps and 1 droplet/step.
Figure 5

Drug-laden reservoirs (A) R100-20 filled in 14 steps and 3 droplets/step; (B) R100-20 filled in 42 steps and 1 droplet/step; (C) R100-50 filled in 42 steps and 1 droplet/step.

4 Conclusion

This study demonstrates drug deposition into micro-sized reservoirs according to the characteristics of the drug solution, operating parameters of the printhead and geometric parameters of the reservoir. In addition, a feasible manufacturing method for micro-sized reservoirs is shown.

In the shown setup of drug deposition, effects such as wettability may have an important influence, especially when the used solvent shows a high wettability of metal surfaces, as is the case for EtOH. It is indicated that there is the need to figure out an optimal ratio between droplet volume and the volume of the reservoir to be loaded. In further investigations the deposition process will be tested using more variations of reservoirs and solvents.

Acknowledgement

The authors wish to acknowledge the skillful assistance of Franz Stachitz.

Author’s Statement

Research funding: We would like to thank the “Bundesministerium für Bildung und Forschung” (BMBF) for financial support for RESPONSE – Partnerschaft für Innovation in der Implantattechnologie. This support is provided with financial resources by the program “Zwanzig20 – Partnerschaft für Innovation”, hosted by BMBF. We would also like to thank the “Ministerium für Wirtschaft, Bau und Tourismus”, Mecklenburg-Vorpommern which provided funding of the Gesim Nanoplotter 2.1 with financial resources via ERDF. Conflict of interest: Authors state no conflict of interest. Material and Methods: Informed consent: Informed consent has been obtained from all individuals included in this study Ethical approval: The research related to human use complies with all the relevant national regulations, institutional policies and was performed in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

References

[1] Jeon G, Yang SY, Kim JK. Funcional nanoporous membranes for drug delivery. J Mater Chem. 2012;22:14814-34.10.1039/c2jm32430jSearch in Google Scholar

[2] Sternberg K, Petersen S, Grabow N, Senz V, Meyer zu Schwabedissen H, Kroemer HK, et al. Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications. Biomed Tech (Berl). 2013;58:417–27.10.1515/bmt-2012-0049Search in Google Scholar PubMed

[3] Löbler M, Sternberg K, Stachs O, Allemann R, Grabow N, Roock A, et al. Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery. J Biomed Mater Res. 2011;97B:388–95.10.1002/jbm.b.31826Search in Google Scholar PubMed

[4] Ceschi P, Bohl A, Sternberg K, Neumeister A, Senz V, Schmitz KP, et al. Biodegradable polymeric coatings on cochlear implant surfaces and their influence on spiral ganglion cell survival. J. Biomed Mater Res. 2014;102:1255–67.10.1002/jbm.b.33110Search in Google Scholar PubMed

[5] Chen W, Habraken TC, Hennink WE, Kok RJ. Polymer-free drug eluting stents: an overview of coating strategies and comparison with polymer-coated drug-eluting stents. Bioconjugate Chem. 2015;26:1277-88.10.1021/acs.bioconjchem.5b00192Search in Google Scholar PubMed

[6] Hsiao HM, Chiu YH, Wu TY, Shen JK, Lee TY. Effects of through-hole drug reservoirs on key clinical attributes for drug-eluting depot stent. Med Eng Phys. 2013;35:884-97.10.1016/j.medengphy.2012.08.021Search in Google Scholar PubMed

[7] Vehse M, Gieseke M, Fiedler S, Petersen S, Irsig R, Senz V, et al. Loading method for discrete drug depots on implant surfaces. Biomed Tech. 2012;57:1089–92.10.1515/bmt-2012-4006Search in Google Scholar

Published Online: 2016-9-30
Published in Print: 2016-9-1

©2016 Robert Mau et al., licensee De Gruyter.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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https://doi.org/10.1515/cdbme-2016-0086
Keywords for this article
drop-on-demand; droplet deposition; drug reservoir; inkjet printing; polymer-free drug delivery system
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  72. Evaluation of an app-based stress protocol
  73. Medication process in Styrian hospitals
  74. Control tower to surgical theater
  75. Development of a skull phantom for the assessment of implant X-ray visibility
  76. Surgical navigation with QR codes
  77. Investigation of the pressure gradient of embolic protection devices
  78. Computer assistance in femoral derotation osteotomy: a bottom-up approach
  79. Automatic depth scanning system for 3D infrared thermography
  80. A service for monitoring the quality of intraoperative cone beam CT images
  81. Resectoscope with an easy to use twist mechanism for improved handling
  82. In vitro simulation of distribution processes following intramuscular injection
  83. Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs
  84. A flexible standalone system with integrated sensor feedback for multi-pad electrode FES of the hand
  85. Smart control for functional electrical stimulation with optimal pulse intensity
  86. Tactile display on the remaining hand for unilateral hand amputees
  87. Effects of sustained electrical stimulation on spasticity assessed by the pendulum test
  88. An improved tracking framework for ultrasound probe localization in image-guided radiosurgery
  89. Improvement of a subviral particle tracker by the use of a LAP-Kalman-algorithm
  90. Learning discriminative classification models for grading anal intraepithelial neoplasia
  91. Regularization of EIT reconstruction based on multi-scales wavelet transforms
  92. Assessing MRI susceptibility artefact through an indicator of image distortion
  93. EyeGuidance – a computer controlled system to guide eye movements
  94. A framework for feedback-based segmentation of 3D image stacks
  95. Doppler optical coherence tomography as a promising tool for detecting fluid in the human middle ear
  96. 3D Local in vivo Environment (LivE) imaging for single cell protein analysis of bone tissue
  97. Inside-Out access strategy using new trans-vascular catheter approach
  98. US/MRI fusion with new optical tracking and marker approach for interventional procedures inside the MRI suite
  99. Impact of different registration methods in MEG source analysis
  100. 3D segmentation of thyroid ultrasound images using active contours
  101. Designing a compact MRI motion phantom
  102. Cerebral cortex classification by conditional random fields applied to intraoperative thermal imaging
  103. Classification of indirect immunofluorescence images using thresholded local binary count features
  104. Analysis of muscle fatigue conditions using time-frequency images and GLCM features
  105. Numerical evaluation of image parameters of ETR-1
  106. Fabrication of a compliant phantom of the human aortic arch for use in Particle Image Velocimetry (PIV) experimentation
  107. Effect of the number of electrodes on the reconstructed lung shape in electrical impedance tomography
  108. Hardware dependencies of GPU-accelerated beamformer performances for microwave breast cancer detection
  109. Computer assisted assessment of progressing osteoradionecrosis of the jaw for clinical diagnosis and treatment
  110. Evaluation of reconstruction parameters of electrical impedance tomography on aorta detection during saline bolus injection
  111. Evaluation of open-source software for the lung segmentation
  112. Automatic determination of lung features of CF patients in CT scans
  113. Image analysis of self-organized multicellular patterns
  114. Effect of key parameters on synthesis of superparamagnetic nanoparticles (SPIONs)
  115. Radiopacity assessment of neurovascular implants
  116. Development of a desiccant based dielectric for monitoring humidity conditions in miniaturized hermetic implantable packages
  117. Development of an artifact-free aneurysm clip
  118. Enhancing the regeneration of bone defects by alkalizing the peri-implant zone – an in vitro approach
  119. Rapid prototyping of replica knee implants for in vitro testing
  120. Protecting ultra- and hyperhydrophilic implant surfaces in dry state from loss of wettability
  121. Advanced wettability analysis of implant surfaces
  122. Patient-specific hip prostheses designed by surgeons
  123. Plasma treatment on novel carbon fiber reinforced PEEK cages to enhance bioactivity
  124. Wear of a total intervertebral disc prosthesis
  125. Digital health and digital biomarkers – enabling value chains on health data
  126. Usability in the lifecycle of medical software development
  127. Influence of different test gases in a non-destructive 100% quality control system for medical devices
  128. Device development guided by user satisfaction survey on auricular vagus nerve stimulation
  129. Empirical assessment of the time course of innovation in biomedical engineering: first results of a comparative approach
  130. Effect of left atrial hypertrophy on P-wave morphology in a computational model
  131. Simulation of intracardiac electrograms around acute ablation lesions
  132. Parametrization of activation based cardiac electrophysiology models using bidomain model simulations
  133. Assessment of nasal resistance using computational fluid dynamics
  134. Resistance in a non-linear autoregressive model of pulmonary mechanics
  135. Inspiratory and expiratory elastance in a non-linear autoregressive model of pulmonary mechanics
  136. Determination of regional lung function in cystic fibrosis using electrical impedance tomography
  137. Development of parietal bone surrogates for parietal graft lift training
  138. Numerical simulation of mechanically stimulated bone remodelling
  139. Conversion of engineering stresses to Cauchy stresses in tensile and compression tests of thermoplastic polymers
  140. Numerical examinations of simplified spondylodesis models concerning energy absorption in magnetic resonance imaging
  141. Principle study on the signal connection at transabdominal fetal pulse oximetry
  142. Influence of Siluron® insertion on model drug distribution in the simulated vitreous body
  143. Evaluating different approaches to identify a three parameter gas exchange model
  144. Effects of fibrosis on the extracellular potential based on 3D reconstructions from histological sections of heart tissue
  145. From imaging to hemodynamics – how reconstruction kernels influence the blood flow predictions in intracranial aneurysms
  146. Flow optimised design of a novel point-of-care diagnostic device for the detection of disease specific biomarkers
  147. Improved FPGA controlled artificial vascular system for plethysmographic measurements
  148. Minimally spaced electrode positions for multi-functional chest sensors: ECG and respiratory signal estimation
  149. Automated detection of alveolar arches for nasoalveolar molding in cleft lip and palate treatment
  150. Control scheme selection in human-machine- interfaces by analysis of activity signals
  151. Event-based sampling for reducing communication load in realtime human motion analysis by wireless inertial sensor networks
  152. Automatic pairing of inertial sensors to lower limb segments – a plug-and-play approach
  153. Contactless respiratory monitoring system for magnetic resonance imaging applications using a laser range sensor
  154. Interactive monitoring system for visual respiratory biofeedback
  155. Development of a low-cost senor based aid for visually impaired people
  156. Patient assistive system for the shoulder joint
  157. A passive beating heart setup for interventional cardiology training
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