Picoliter-volume inkjet printing into planar microdevice reservoirs for low-waste, high-capacity drug loading.

Oral delivery of therapeutics is the preferred route for systemic drug administration due to ease of access and improved patient compliance. However, many therapeutics suffer from low oral bioavailability due to low pH and enzymatic conditions, poor cellular permeability, and low residence time. Microfabrication techniques have been used to create planar, asymmetric microdevices for oral drug delivery to address these limitations. The geometry of these microdevices facilitates prolonged drug exposure with unidirectional release of drug toward gastrointestinal epithelium. While these devices have significantly enhanced drug permeability in vitro and in vivo, loading drug into the micron-scale reservoirs of the devices in a low-waste, high-capacity manner remains challenging. Here, we use picoliter-volume inkjet printing to load topotecan and insulin into planar microdevices efficiently. Following a simple surface functionalization step, drug solution can be spotted into the microdevice reservoir. We show that relatively high capacities of both topotecan and insulin can be loaded into microdevices in a rapid, automated process with little to no drug waste

A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples

Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly documented sexually transmitted infections each year. Once appropriately diagnosed, NG infections can be readily treated with antibiotics, but high-risk patients often do not return to the clinic for treatment if results are not provided at the point of care. A rapid, sensitive molecular diagnostic would help increase NG treatment and reduce the prevalence of this sexually transmitted disease. Here, we report on the design and development of a rapid, highly sensitive, paperfluidic device for point-of-care diagnosis of NG. The device integrates patient swab sample lysis, nucleic acid extraction, thermophilic helicase-dependent amplification (tHDA), an internal amplification control (NGIC), and visual lateral flow detection within an 80 min run time. Limits of NG detection for the NG/NGIC multiplex tHDA assay were determined within the device, and clinical performance was validated retroactively against qPCR-quantified patient samples in a proof-of-concept study. This paperfluidic diagnostic has a clinically relevant limit of detection of 500 NG cells per device with analytical sensitivity down to 10 NG cells per device. In triplicate testing of 40 total urethral and vaginal swab samples, the device had 95% overall sensitivity and 100% specificity, approaching current laboratory-based molecular NG diagnostics. This diagnostic platform could increase access to accurate NG diagnoses to those most in need.This work was funded by the National Institute of Health National Institute of Allergy and Infectious Diseases award number R01 AI113927 to Boston University and the NIH National Institute of Biomedical and Bioengineering award number U54 EB007958 to Johns Hopkins University. (R01 AI113927 - National Institute of Health National Institute of Allergy and Infectious Diseases; U54 EB007958 - NIH National Institute of Biomedical and Bioengineering)Accepted manuscrip

Highly flexible, foldable, and rollable microsupercapacitors on an ultrathin polyimide substrate with high power density.

The design and functionality of extremely flexible, foldable, and rollable microsupercapacitors (MSCs) with in-plane interdigital electrodes that consist of single-walled carbon nanotube (SWCNT) networks on an ultrathin polyimide substrate are demonstrated through experiments and finite element simulations. The all-solid-state MSCs can be reversibly bent, folded, and rolled purely elastically without degradation of their electrical performance. The simulation results confirm that the deformation in bent, folded, and rolled MSCs is purely elastic. The high power density (1125 W cm-3) and small time constant (1 ms) of the present MSCs are comparable to those of aluminum electrolytic capacitors. The MSCs operate at scan rates of up to 1000 V s-1, are characterized by a volumetric capacitance of 18 F cm-3 and an energy density of 1.6 mWh cm-3, and exhibit superior electrochemical stability with 96% capacity retention even after 100,000 charge/discharge cycles. The developed MSCs demonstrate high potential for integration in flexible and wearable electronic systems

Design of an innovative polymerase chain reaction device based on buoyancy driven flow

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Polymerase Chain Reaction (PCR) plays a central role in the field of molecular biology. The miniaturization of PCR systems is promising as it potentially minimizes costly reagent consumption and time required for analysis. In PCR microdevices a sample solution is usually handled by external pumps. An alternative solution relies on temperature-induced density difference in the presence of a body force to induce buoyancy driven flow. This alternative method is easy to be used and does not require expensive setup, but, to date, the thermo-fluid-dynamic field in the micro-channels still needs to be optimized. The present study focuses on the design of micro-channels, having innovative and optimized shapes to obtain proper fluid actuation and DNA sample amplification within buoyancy driven flow PCR devices. A parametric study is carried out by means of computational thermal fluid dynamic modeling: several channel geometry configurations were compared in terms of time required for analysis, temperature distribution and priming volume. The advantages and disadvantages of such configurations are discussed

Microfluidic DNA amplification - a review

The application of microfluidic devices for DNA amplification has recently been extensively studied. Here, we review the important development of microfluidic polymerase chain reaction (PCR) devices and discuss the underlying physical principles for the optimal design and operation of the device. In particular, we focus on continuous-flow microfluidic PCR on-chip, which can be readily implemented as an integrated function of a micro-total-analysis system. To overcome sample carryover contamination and surface adsorption associated with microfluidic PCR, microdroplet technology has recently been utilized to perform PCR in droplets, which can eliminate the synthesis of short chimeric products, shorten thermal-cycling time, and offers great potential for single DNA molecule and single-cell amplification. The work on chip-based PCR in droplets is highlighted

Axisymmetric polydimethysiloxane microchannels for in vitro hemodynamic studies

The current microdevices used for biomedical research are often manufactured using microelectromechanical systems (MEMS) technology. Although it is possible to fabricate precise and reproducible rectangular microchannels using soft lithography techniques, this kind of geometry may not reflect the actual physiology of the microcirculation. Here, we present a simple method to fabricate circular polydimethysiloxane (PDMS) microchannels aiming to mimic an in vivo microvascular environment and suitable for state-of-the-art microscale flow visualization techniques, such as confocal µPIV/PTV. By using a confocal µPTV system individual red blood cells (RBCs) were successfully tracked trough a 75 µm circular PDMS microchannel. The results show that RBC lateral dispersion increases with the volume fraction of RBCs in the solution, i.e. with the hematocrit

Giant Planar Hall Effect in Epitaxial (Ga,Mn)As Devices

Large Hall resistance jumps are observed in microdevices patterned from epitaxial (Ga,Mn)As layers when subjected to a swept, in-plane magnetic field. This giant planar Hall effect is four orders of magnitude greater than previously observed in metallic ferromagnets. This enables extremely sensitive measurements of the angle-dependent magnetic properties of (Ga,Mn)As. The magnetic anisotropy fields deduced from these measurements are compared with theoretical predictions.Comment: 3 figure

Implantable Unpowered Parylene MEMS Intraocular Pressure Sensor

This paper presents the first implantable, unpowered, parylene-based micro-electro-mechanical-systems (MEMS) pressure sensor for intraocular pressure (IOP) sensing. From in situ mechanical deformation of the compliant structures, this sensor registers pressure variations without power consumption/transduction. Micromachined high-aspect-ratio thin-walled tubes in different geometric layouts are exploited to obtain a high-sensitivity pressure response. An integrated packaging method has been successfully developed to realize suture-less implantation of the device. In vitro testing results have demonstrated that the IOP sensor can achieve 0.67 degree/mmHg angular sensitivity with a spiral-tube design, 3.43 µm/mmHg lateral sensitivity with a long-armed-tube design, and 0.38 µm/mmHg longitudinal sensitivity with a serpentine-tube design. This IOP sensor is designed to be implanted in the anterior chamber of the eye and anchored directly on the iris so that, under incident visible light, the pressure response of the implant can be directly observed from outside the eye, which enables faithful and unpowered IOP monitoring in glaucoma patient