Tingrui Pan

Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork

PURPOSE Elevated intraocular pressure (IOP) is a risk factor for glaucoma. The principal outflow pathway for aqueous humor in the human eye is through the trabecular meshwork (HTM) and Schlemms canal (SC). The junction between the HTM and SC is thought to have a significant role in the regulation of IOP. A possible mechanism for the increased resistance to flow in glaucomatous eyes is an increase in stiffness (increased elastic modulus) of the HTM. In this study, the stiffness of the HTM in normal and glaucomatous tissue was compared, and a mathematical model was developed to predict the impact of changes in stiffness of the juxtacanalicular layer of HTM on flow dynamics through this region. METHODS Atomic force microscopy (AFM) was used to measure the elastic modulus of normal and glaucomatous HTM. According to these results, a model was developed that simulated the juxtacanalicular layer of the HTM as a flexible membrane with embedded pores. RESULTS The mean elastic modulus increased substantially in the glaucomatous HTM (mean = 80.8 kPa) compared with that in the normal HTM (mean = 4.0 kPa). Regional variation was identified across the glaucomatous HTM, possibly corresponding to the disease state. Mathematical modeling suggested an increased flow resistance with increasing HTM modulus. CONCLUSIONS The data indicate that the stiffness of glaucomatous HTM is significantly increased compared with that of normal HTM. Modeling exercises support substantial impairment in outflow facility with increased HTM stiffness. Alterations in the biophysical attributes of the HTM may participate directly in the onset and progression of glaucoma.

A magnetically driven PDMS micropump with ball check-valves

In this paper, we present a low-cost, PDMS-membrane micropump with two one-way ball check-valves for lab-on-a-chip and microfluidic applications. The micropump consists of two functional PDMS layers, one holding the ball check-valves and an actuating chamber, and the other covering the chamber and holding a miniature permanent magnet on top for actuation. An additional PDMS layer is used to cover the top magnet, and thereby encapsulate the entire device. A simple approach was used to assemble a high-performance ball check-valve using a micropipette and heat shrink tubing. The micropump can be driven by an external magnetic force provided by another permanent magnet or an integrated coil. In the first driving scheme, a small dc motor (6 mm in diameter and 15 mm in length) with a neodymium–iron–boron permanent magnet embedded in its shaft was used to actuate the membrane-mounted magnet. This driving method yielded a large pumping rate with very low power consumption. A maximum pumping rate of 774 µL min−1 for deionized water was achieved at the input power of 13 mW, the highest pumping rate reported in the literature for micropumps at such power consumptions. Alternatively, we actuated the micropump with a 10-turn planar coil fabricated on a PC board. This method resulted in a higher pumping rate of 1 mL min−1 for deionized water. Although more integratable and compact, the planar microcoil driving technique has a much higher power consumption.

Mechanochemotransduction During Cardiomyocyte Contraction Is Mediated by Localized Nitric Oxide Signaling

Nitric oxide exposed to mechanical stress reveals the chemical cues involved in altering Ca2+ signals that lead to arrhythmias. Pulling Harder on the Heartstings To eject blood, a beating heart must contract against afterload, the buildup of mechanical tension in the left ventricle, which imposes mechanical stress. Calcium signaling increases in cardiomyocytes in a beating heart to enhance the strength of the muscular contraction to cope with afterload. However, this increase in calcium signaling can lead to arrhythmias. Jian et al. analyzed cardiomyocytes embedded in a gel matrix that imposed mechanical strain resembling afterload and found that nitric oxide generated near ryanodine receptors, a group of intracellular calcium channels, contributed to the afterload-induced increase in calcium signaling. These results identify potential therapeutic targets for treating various heart diseases that are caused by excessive mechanical stress or dysregulated Ca2+ signaling. Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca2+ dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca2+ transient, which enhanced contractility to counter mechanical load but also caused spontaneous Ca2+ sparks during diastole that could be arrhythmogenic. The increases in the Ca2+ transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2+ in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2+ sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca2+-calmodulin–dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca2+ sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca2+ sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2+ sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress–induced Ca2+ dysregulation, arrhythmias, and cardiomyopathy.

Flexible Transparent Iontronic Film for Interfacial Capacitive Pressure Sensing

A flexible, transparent iontronic film is introduced as a thin-film capacitive sensing material for emerging wearable and health-monitoring applications. Utilizing the capacitive interface at the ionic-electronic contact, the iontronic film sensor offers a large unit-area capacitance (of 5.4 μF cm(-2) ) and an ultrahigh sensitivity (of 3.1 nF kPa(-1) ), which is a thousand times greater than that of traditional solid-state counterparts.

Droplet-driven transports on superhydrophobic-patterned surface microfluidics.

Droplet-based transport phenomena driven by surface tension have been explored as an automated pumping source for a number of chemical and biological applications. In this paper, we present a comprehensive theoretical and experimental investigation of unconventional droplet-based motions on a superhydrophobic-patterned surface microfluidic (S(2)M) platform. The S(2)M surfaces are monolithically fabricated using a facile two-step laser micromachining technique on regular polydimethylsiloxane (PDMS) chemistry. Unlike the traditional droplet-driven pumps built on an enclosed microfluidic network, the S(2)M network pins the liquid-solid interface of droplets to the lithographically defined wetting boundary and establishes a direct linkage between the volumetric and hydraulic measures. Moreover, diverse modes of droplet motions are theoretically determined and experimentally characterized in a bi-droplet configuration, among which several unconventional droplet-driven transport phenomena are first demonstrated. These include big-to-small droplet merging, droplet balancing, as well as bidirectional transporting, in addition to the classic small-to-big droplet transition. Furthermore, multi-stage programmable bidirectional pumping has been implemented on the S(2)M platform, according to the newly established droplet manipulation principle, to illustrate its potential use for automated biomicrofluidic and point-of-care diagnostic applications.

From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities.

Endogenous electric currents might guide rostral migration of neuroblasts

Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 μA/cm2, average field strength of ∼3 mV/mm) along the rostral migration path in adult mouse brain. Electric fields of similar strength direct migration of neuroblasts from the SVZ in culture and in brain slices. The purinergic receptor P2Y1 mediates this migration. The results indicate that naturally occurring electric currents serve as a new guidance mechanism for rostral neuronal migration.

A reworkable adhesive-free interconnection technology for microfluidic systems

In this paper, we present a simple adhesive-free interconnect technology for microfluidic systems. Reliable connection between microfluidic devices and macroscopic world is a critical issue in many lab-on-a-chip applications. In such interconnections, it is particularly advantageous to avoid liquid adhesives (e.g., epoxy, silicone, etc.) since they can create reliability (blockage or leakage) and reproducibility problems. Our adhesive-free interconnection technology is based on a micromachined silicon flange which is connected to a medical-grade silastic tube using a heat shrink tubing sleeve. The silicon part was fabricated by consecutive anisotropic and isotropic etching processes resulting in a through-hole surrounded by a connection socket ring created using the well known lag effect of deep reactive ion etching. Biocompatible polyolefin heat shrink tubing (expansion ratio of 2:1 at its shrink temperature of 143/spl deg/C) was used to connect and tightly seal the silicon flange to the silastic tube without application of any adhesive. A two-step heat treatment starting from the silicon flange and terminating at the silastic tubing was used to seal the connection. High temperature removability of the heat shrink tubing makes interconnects reworkable. Pull-out force was measured to test the mechanical strength of interconnects with different socket shapes (square, hexagon, octagon, and 32-side circle). Increasing the number of sides improves the mechanical strength with the circular interconnects having an average pull-out force of more than 3N. Leakage tests were also performed to characterize the seal quality. The circular connectors of two different flange sizes showed zero leakage up to the maximum test pressure of 200 kPa (29 psi).

Photopatternable Superhydrophobic Nanocomposites for Microfabrication

In this paper, we first report on direct-photolithography-based microfabrication of transparent super-hydrophobic micropatterns using novel photodefinable nanocomposites, combining the nanomorphology and hydrophobicity of polytetrafluoroethylene (PTFE) nanoparticles and the photopatternability and transparency of an SU-8 photoresist using both direct-mixing and coating-immobilization methods. The direct mixture of PTFE-SU-8 nanocomposite can be reliably spin-coated and photopatterned onto transparent substrates (e.g., glass or polymers) with a minimal feature resolution of 50 ¿m. The resulting nanocomposite film possesses a contact angle of water at 150°, although its optical transparency is less than 30%. Furthermore, a modified coating-immobilization approach, employing spray coating and thermal immobilization of PTFE nanoparticles onto an SU-8 polymer matrix, significantly enhances superhydrophobicity, lithography resolution, as well as optical transparency. The highest optical transparency of 80% and a minimal feature resolution of 10 ¿m have been achieved using the standard photolithography approach, while the contact angle of water above 165° enables extraordinary superhydrophobicity with low hysteresis. The novel PTFE-SU-8 nanocomposites provide a unique combination of superhydrophobicity, optical transparency, and photopatternability, along with excellent adaptability and simple processability, which offer great extension to rapidly evolving micro-nanoengineering applications.

Droplet-based interfacial capacitive sensing

This paper presented a novel droplet-based pressure sensor using elastic and capacitive electrode-electrolyte interfaces to achieve ultrahigh mechanical-to-electrical sensitivity (1.58 μF kPa(-1)) and resolution (1.8 Pa) with a simple device architecture. The miniature transparent droplet sensors, fabricated by one-step laser micromachining, consisted of two flexible polymer membranes with conductive coating and a separation layer hosting a sensing chamber for an electrolyte droplet. The sensing principle primarily relied on high elasticity of the sensing droplet and large capacitance presented at the electrode-electrolyte interface. A simple surface modification scheme was introduced to the conductive coating, which reduced hysteresis of the droplet deformation without substantially compromising the interfacial capacitance. Moreover, the major concern of liquid evaporation was addressed by a mixture of glycerol and electrolyte with long-term stability in a laboratory environment. Theoretical analyses and experimental investigations on several design parameters (i.e., the dimensions of the sensing chamber and the droplet size) were thoroughly conducted to characterize and optimize the overall sensitivity of the device. Moreover, the environmental influences (e.g., temperature and humidity) on the capacitive measurement were further investigated. Finally, the simply constructed and mechanically flexible droplet sensor was successfully applied to detect minute blood pressure variations on the skin surface (with the maximum value less than 100 Pa) throughout cardiovascular cycles.