This PDF file contains the front matter associated with SPIE Proceedings Volume 12374, including the Title Page, Copyright information, Table of Contents and Conference Committee lists.

3D bioprinting technology has promising applications in regenerative medicine and drug testing in the near future for the fabrication of patient-specific replicas of human organs, bones, etc. Previously, we have developed a dual-arm 3D bioprinting system, TwinPrint, using two robots to cooperatively bioprint peptide-based soft matter structures. During 3D bioprinting, optimization of extrusion flow rates of peptide bioinks is critical for efficient cell encapsulation and mechanical stability. Currently, it is dependent on user knowledge and experience from past experiments which may vary in reliability and quality. Thus, this paper proposes a multi-output regression machine learning model to predict optimized peptide flow rates for the microfluidic-based pumping component of the TwinPrint system. Specifically, parameters including peptide bioink type, peptide concentration, phosphate-buffered saline (PBS) concentration and nozzle size are used as inputs for machine learning methods. The output is estimated optimal flow rates of the bioink fluid components, essential in obtaining a consistent amount of gel extrusion. The dataset used to train and test the predictive model is collected from numerous bioprinting experiments conducted on-site. Performance evaluation metrics are applied to examine and assess the developed model, which is incorporated within our in-house developed TwinPrint software to automatically suggest flow rates once the user specifies initial parameters. Finally, the flow rate predictive software in conjunction with the advanced dual-arm robotic system hardware are demonstrated in this work to pave the way for automated optimization of 3D bioprinting for enhanced printability, repeatability and standardization

Microneedles are an emerging technology that offer an alternative to traditional hypodermic needles for drug and vaccine delivery. Less than 1 mm in length, microneedles can penetrate the skin with little to no pain making them a suitable option for the 1-in-10 people that may avoid seeking medical care due to needle phobia. However, there are significant challenges with adapting existing microneedle fabrication methods for large scale manufacturing while matching the repeatability, reliability, and cost of current hypodermic needle mass production processes. In this work we present a novel method of fabricating microneedles using a modified automated wire bonding process that is highly suited for mass production due to existing widespread use of this process and equipment in the semiconductor industry. Microneedle arrays of different densities were fabricated on FR-4 based printed circuit board substrates using this automated process and tested by inserting into porcine skin tissue to determine insertion forces. The required insertion force generally increased with increasing array density due to the “bed of nails” effect and decreased with increasing insertion speed due to the viscoelastic properties of porcine skin tissue. Characterizing the correlations between insertion force, insertion speed, and array density are important for designing microneedle-based devices and applicators that can reliably penetrate skin. Microneedle arrays were also successfully created by automated wire bonding on polyimide-based printed circuit boards to demonstrate that this process can be done on flexible substrates. Further investigation with larger samples sizes is required to expand on the preliminary findings of this work.

Organoids are three-dimensional structures of self-assembled cell aggregates that mimic anatomical features of in vivo organs and, therefore, can serve as in vitro miniaturized organ models for drug testing. The most effective way of studying drug toxicity and efficacy requires fast-paced and high-resolution imaging of organoids which is possible by first immobilizing the organoids. However, suitable platforms that are conducive to high-throughput imaging and can fully immobilize the organoids are missing. We propose a unique microfluidic device capable of hydrogel-free immobilization of cardiac organoids in predetermined locations for viability staining and calcium-transients imaging without compromising their morphology and behavior. In doing so, we treated cardiac organoids with Doxorubicin (DOX), and successfully immobilized and imaged them within our device to evaluate organoid viability upon treatment.

During the COVID-19 pandemic, point-of-care genetic testing (POCT) devices were used for on-time and on-site detection of the virus, which helped to prevent and control the spread of the pandemic. Smartphones, which are widely used electronic devices with many functions, have the potential to be used as a molecular diagnostic platform for universal healthcare monitoring. Several integrated diagnostics platforms for the real-time and end-point detection of COVID-19 were developed using the functions of smartphones, such as the operating system, power, sound, camera, data storage, and display. These platforms use the 5V output power of smartphones, which can be amplified to power a micro-capillary electrophoresis system or a thin-film heater, and the CMOS camera of smartphones can capture the color change during a colorimetric loop-mediated isothermal amplification test and detect fluorescence signals. Smartphones can also be used with self-written web-based apps to enable automatic and remote pathogen analysis on POCT platforms. Our lab developed a handheld micro-capillary electrophoresis device for end-point detection of SARS-CoV-2, as well as an integrated smartphone-based genetic analyzer for the qualitative and quantitative colorimetric detection of foodborne pathogens with the help of a custom mobile app.

Geological sequestration of CO2 in the pore space of subsurface rock formations offers a safe and permanent carbon storage solution. In this work, we present the application of a pore-scale flow simulator to the study of CO2 storage in geological formations. We model the rock pore space geometry, extracted from high-resolution X-ray microtomography images of suitable rocks as a network of connected capillaries. Assuming piston-like flow within each capillary and conservation of mass at each network node, a large system of equations can be solved to compute properties like pressure distribution or flow rate at each point in the network. Multi-phase flow simulations track the displacement in time of the fluid interface within each capillary. These dynamic simulations on the high-resolution capillary network representation of the rock are very computationally costly. Alternatively, analysis is carried out on the aggregate results of multiple two-phase flow simulations on several statistically equivalent capillary network models of the rock sample, which retain topological properties of the original at a significantly lower computational cost. We performed a sensitivity analysis with respect to multiple fluid parameters, such as viscosity, interfacial tension, contact angle, pressure, and temperature, and quantify their influence on the infiltration and retention of CO2 inside a capillary network that is representative of an actual rock.

Detection and quantification of bacterial populations in droplets is a fundamental prerequisite for the application of droplet microfluidic technology in antibiotic susceptibility assays, paving the way for single-cell profiling and quantifying hetero-resistance. While several label-free detection approaches have been proposed, limited detection sensitivity and the ability to quantify bacterial populations in droplets accurately remain challenging. Furthermore, these approaches are prone to a high number of false positives resulting in low accuracy and requiring highly monodisperse droplets. This study presents a speckle image-based detection technique for the quantification of the bacterial population in droplets. Speckles are generated by scattering laser light from bacteria-loaded droplets in a flow cytometric approach. Spatial segregation of the scattering signal from the droplet surface as well as its contents allows the detection of encapsulated bacteria with a high signal-to-noise ratio. This results in a detection sensitivity of ⁓100 CFU/droplet, the highest achieved by any label-free detection technique in a flow format thus far. It also allows the identification of false-positive signals, thereby increasing the accuracy of detection and enabling operation with polydisperse droplets (diameter: 10–500 µm). The properties of the speckle image generated from droplets, such as speckle grain size and density, can be used to quantify the population of bacteria in droplets. This detection approach applies to a wide range of bacteria species of clinical and industrial importance, creating avenues for innovation in bacteria analysis using droplet microfluidics.

Implementation of microsystems on flexible substrates has enabled a new class of noninvasive medical devices. Flexible substrates are interfaced with soft tissues without causing damage or discomfort for the users. This will enable noninvasive attachment of medical microsystems to the surface of fragile tissues such as infants’ skin. In this talk, we will introduce two noninvasive medical microsystems on flexible substrates: a smart, wireless, battery-free, chipless patch for detection of cutaneous melanoma and a Band-Aid-like conductive hearing aid for pediatric patients. The patch will be placed on the epidermis layer for detection of abnormality in impedance of skin, and the flexible hearing aid will be attached to an infant’s skin behind the ear to bypass pediatric conductive hearing loss. These technologies will enable early action on melanoma and pediatric hearing loss, avoiding long-term consequences of these diseases.

Implantable conductive hearing aids are invasive for infants’ fragile cranial cortices, and the nonsurgical rigid aids often become displaced and may cause skin irritation for pediatric patients. Micro-epidermal actuators on a flexible substrate generate vibrations on the surface of the skin for noninvasive Band-Aid©-like conductive hearing aids. However, the major challenges are to increase the strength of vibration transmission to the cranial cortex from the thin actuator and to overcome vibration damping due to flexible substrate and soft skin. Here we designed and fabricated two micro epidermal actuators to increase coupling from the actuator to the bone. We used a laser Doppler vibrometer to measure the transmissibility of vibrations for a piezoelectric actuator. We also measured the mode of vibrations and acceleration for two designs. Our results show that vibrations are transmitted from the actuator to a rigid foundation more efficiently when a piezoelectric actuator is embedded into the flexible substrate.

Fabrication of Microfluidic devices have gained popularity in a wide range of application demanding fluid flow control such as Anti-microbial resistance, Integrated blood test systems, drug delivery system, protein separation, DNA extraction, in- vitro diagnostic studies, lab-on-a-chip, organ-on-a-chip, inkjet printers and other industrial sensors. Fluid flow regulation, on/off switching and sealing of fluids can be achieved by incorporating Microvalves. The shape of the microvalve plays a key role in desired actuation of the microvalves. Therefore, a detailed study of various structures of the microvalve is crucial. This work discusses about the stability and reliability of different microvalve shapes. Simulation work gives a comparative study showcasing the displacement of the microvalve thin film polymer layer on account of applied pressure on several shapes of same area. Furthermore, details of stress distribution for the same has been carried out. The analysis focusses on the circular, elliptical and capsule shapes of the microvalve. The comparative study of the simulation results revealed that the maximum stress experienced by the microvalves of circular shape is 1.1 times lower than that of elliptical shape. While, circular shape microvalve shows 1.22 times lower stress when compared to capsule shape. In addition, displacement of the circular shape microvalve is 1.33 and 1.31 times greater than elliptical and capsule shapes for the same area and applied pressure respectively. The study manifests that the circular shape microvalve performance indicate better stable actuation when compared to the rest of the shapes. Microfabrication of the same is carried out using dry film photoresist which is highly cost effective.