Additively Manufactured Detection Module with Integrated Tuning Fork for Enhanced Photo-Acoustic Spectroscopy.

Starting from Quartz-Enhanced Photo-Acoustic Spectroscopy (QEPAS), we have explored the potential of a tightly linked method of gas/vapor sensing, from now on referred to as Tuning-Fork-Enhanced Photo-Acoustic Spectroscopy (TFEPAS). TFEPAS utilizes a non-piezoelectric metal or dielectric tuning fork to transduce the photoacoustic excitation and an optical interferometric readout to measure the amplitude of the tuning fork vibration. In particular, we have devised a solution based on Additive Manufacturing (AM) for the Absorption Detection Module (ADM). The novelty of our solution is that the ADM is entirely built monolithically by Micro-Metal Laser Sintering (MMLS) or other AM techniques to achieve easier and more cost-effective customization, extreme miniaturization of internal volumes, automatic alignment of the tuning fork with the acoustic micro-resonators, and operation at high temperature. This paper reports on preliminary experimental results achieved with ammonia at parts-per-million concentration in nitrogen to demonstrate the feasibility of the proposed solution. Prospectively, the proposed TFEPAS solution appears particularly suited for hyphenation to micro-Gas Chromatography and for the analysis of complex solid and liquid traces samples, including compounds with low volatility such as illicit drugs, explosives, and persistent chemical warfare agents.

3-D Printed Adjustable Microelectrode Arrays for Electrochemical Sensing and Biosensing.

Printed Electronics has emerged as an important fabrication technique that overcomes several shortcomings of conventional lithography and provides custom rapid prototyping for various sensor applications. In this work, silver microelectrode arrays (MEA) with three different electrode spacing were fabricated using 3-D printing by the aerosol jet technology. The microelectrodes were printed at a length scale of about 15 µm, with the space between the electrodes accurately controlled to about 2 times (30 µm, MEA30), 6.6 times (100 µm, MEA100) and 12 times (180 µm, MEA180) the trace width, respectively. Hydrogen peroxide and glucose were chosen as model analytes to demonstrate the performance of the MEA for sensor applications. The electrodes are shown to reduce hydrogen peroxide with a reduction current proportional to the concentration of hydrogen peroxide for certain concentration ranges. Further, the sensitivity of the current for the three electrode configurations was shown to decrease with an increase in the microelectrode spacing (sensitivity of MEA30: MEA100: MEA180 was in the ratio of 3.7: 2.8: 1), demonstrating optimal MEA geometry for such applications. The noise of the different electrode configurations is also characterized and shows a dramatic reduction from MEA30 to MEA100 and MEA180 electrodes. Further, it is shown that the response current is proportional to MEA100 and MEA180 electrode areas, but not for the area of MEA30 electrode (the current density of MEA30 : MEA100 : MEA180 is 0.25 : 1 : 1), indicating that the MEA30 electrodes suffer from diffusion overlap from neighboring electrodes. The work thus establishes the lower limit of microelectrode spacing for our geometry. The lowest detection limit of the MEAs was calculated (with S/N = 3) to be 0.45 µM. Glucose oxidase was immobilized on MEA100 microelectrodes to demonstrate a glucose biosensor application. The sensitivity of glucose biosensor was 1.73 µAmM-1 and the calculated value of detection limit (S/N = 3) was 1.7 µM. The electrochemical response characteristics of the MEAs were in agreement with the predictions of existing models. The current work opens up the possibility of additive manufacturing as a fabrication technique for low cost custom-shaped MEA structures that can be used as electrochemical platforms for a wide range of sensor applications.

3D Printing of Reservoir Devices for Oral Drug Delivery: From Concept to Functionality through Design Improvement for Enhanced Mucoadhesion.

So far, microdevices for oral drug delivery have been fabricated as square or cylindrical reservoir structures with a localized and unidirectional release. The fabrication is usually carried out using sophisticated and costly microfabrication techniques. Here, 3D printing of microreservoirs on sacrificial substrates is presented. This approach allows the devices to be accurately arranged in predetermined patterns, enabling implementation into batch production schemes in which the fabrication of the devices is linked to processing steps such as automated drug loading and sealing. Moreover, design and 3D printing of alternative geometries of minireservoirs featuring anchor-like surface structures for improved mucoadhesion and intestinal retention is demonstrated. Surface texturing of minireservoirs increases mucoadhesion of the devices up to two-fold compared to a nonstructured control. The structuring also leads to a strong bias in mucoadhesion in different orientations, which can facilitate a correct orientation of the devices and thus lead to unidirectional release of drugs toward the intestinal mucosa for increased drug uptake.

Modeling and Experimental Study of the Localized Electrochemical Micro Additive Manufacturing Technology Based on the FluidFM.

In this work, the localized electrochemical micro additive manufacturing technology based on the FluidFM (fluidic force microscope) has been introduced to fabricate micro three-dimensional overhang metal structures at sub-micron resolution. It breaks through the localized deposition previously achieved by micro-anode precision movement, and the micro-injection of the electrolyte is achieved in a stable electric field distribution. The structure of electrochemical facilities has been designed and optimized. More importantly, the local electrochemical deposition process has been analyzed with positive source diffusion, and the mathematical modeling has been revealed in the particle conversion process. A mathematical model is proposed for the species flux under the action of pulsed pressure in an innovatively localized liquid feeding process. Besides, the linear structure, bulk structure, complex structure, and large-area structure of the additive manufacturing are analyzed separately. The experimental diameter of the deposited cylinder structure is linearly fitted. The aspect ratio of the structure is greater than 20, the surface roughness value is between 0.1-0.2 µm at the surface of bulk structures, and the abilities are verified for deposition of overhang, hollow complex structures. Moreover, this work verifies the feasibility of 3D overhang array submicron structure additive manufacturing, with the application of pulsed pressure. Furthermore, this technology opens new avenues for the direct fabrication of nano circuit interconnection, tiny sensors, and micro antennas.

Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination.

The skin is an attractive tissue target for vaccination, as it is readily accessible and contains a dense population of antigen-presenting and immune-accessory cells. Microneedle arrays (MNAs) are emerging as an effective tool for in situ engineering of the cutaneous microenvironment to enable diverse immunization strategies. Here, we present novel dissolving undercut MNAs and demonstrate their application for effective multicomponent cutaneous vaccination. The MNAs are composed of micron-scale needles featuring pyramidal heads supported by undercut stem regions with filleted bases to ensure successful skin penetration and retention during application. Prior efforts to fabricate dissolving undercut microstructures were limited and required complex and lengthy processing and assembly steps. In the current study, we strategically combine three-dimensional (3D) laser lithography, an emerging micro-additive manufacturing method with unique geometric capabilities and nanoscale resolution, and micromolding with favorable materials. This approach enables reproducible production of dissolving MNAs with undercut microneedles that can be tip-loaded with multiple biocargos, such as antigen (ovalbumin) and adjuvant (Poly(I:C)). The resulting MNAs fulfill the geometric (sharp tips and smooth edges) and mechanical-strength requirements for failure-free penetration of human and murine skin to simultaneously deliver multicomponent (antigen plus adjuvant) vaccines to the same cutaneous microenvironment. Cutaneous vaccination of mice using these MNAs induces more potent antigen-specific cellular and humoral immune responses than those elicited by traditional intramuscular injection. Together, the unique geometric features of these undercut MNAs and the associated manufacturing strategy, which is compatible with diverse drugs and biologics, could enable a broad range of non-cutaneous and cutaneous drug delivery applications, including multicomponent vaccination.

Manipulation and Localized Deposition of Particle Groups with Modulated Electric Fields.

This paper presents a new micro additive manufacturing process and initial characterization of its capabilities. The process uses modulated electric fields to manipulate and deposit particles from colloidal solution in a contactless way and is named electrophoretically-guided micro additive manufacturing (EPµAM). The inherent flexibility and reconfigurability of the EPµAM process stems from electrode array as an actuator use, which avoids common issues of controlling particle deposition with templates or masks (e.g., fixed template geometry, post-process removal of masks, and unstable particle trapping). The EPµAM hardware testbed is presented alongside with implemented control methodology and developed process characterization workflow. Additionally, a streamlined two-dimensional (2D) finite element model (FEM) of the EPµAM process is used to compute electric field distribution generated by the electrode array and to predict the final deposition location of particles. Simple particle manipulation experiments indicate proof-of-principle capabilities of the process. Experiments where particle concentration and electric current strength were varied demonstrate the stability of the process. Advanced manipulation experiments demonstrate interelectrode deposition and particle group shaping capabilities where high, length-to-width, aspect ratio deposits were obtained. The experimental and FEM results were compared and analyzed; observed process limitations are discussed and followed by a comprehensive list of possible future steps.

Customized fast-separable microneedles prepared with the aid of 3D printing for nanoparticle delivery.

3D printing of master molds for soft lithography-based fabrication of microneedles (MNs) is a cost effective, easy and fast method for producing MNs with variable designs. Deviating from the classical geometries of MNs, 'tanto blade'-inspired MNs showed effective skin penetration, acting as sharp structures with low insertion force of 10.6 N, which is sufficient for manual insertion. Additionally, hydrophilic, fluorescent noble metal nanocluster-modified gelatin nanocarriers were loaded in polyvinyl alcohol/sucrose MNs to act as a novel potential theranostic system emitting light in the near-infrared (λem = ~700 nm). Nanoparticles (NPs) distribution within the MNs and release have been monitored using confocal laser scanning microscopy by means of spectral analysis and linear unmixing. Furthermore, the MNs patch was modified by carving a channel at each of the four corners of the patch. This facilitated the separation process of MNs from the patch base into skin, when 15 µL phosphate buffered saline was applied through each channel post-skin insertion of the MNs. Then, the patch base can be removed easily leaving the implanted MNs inside the skin for further release of the NP cargo. This successfully reduced the application time to 1 min for enhanced patient compliance.