Microfluidic-based systems for the management of diabetes.

Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature.

Reconsidering tympanal-acoustic interactions leads to an improved model of auditory acuity in a parasitoid fly.

Although most binaural organisms locate sound sources using neurological structures to amplify the sounds they hear, some animals use mechanically coupled hearing organs instead. One of these animals, the parasitoid flyOrmia ochracea(O. ochracea), has astoundingly accurate sound localization abilities. It can locate objects in the azimuthal plane with a precision of 2°, equal to that of humans, despite an intertympanal distance of only 0.5 mm, which is less than1/100th of the wavelength of the sound emitted by the crickets that it parasitizes.O. ochraceaaccomplishes this feat via mechanically coupled tympana that interact with incoming acoustic pressure waves to amplify differences in the signals received at the two ears. In 1995, Mileset aldeveloped a model of hearing mechanics inO. ochraceathat represents the tympana as flat, front-facing prosternal membranes, though they lie on a convex surface at an angle from the flies' frontal and transverse planes. The model works well for incoming sound angles less than±30∘but suffers from reduced accuracy (up to 60% error) at higher angles compared to response data acquired fromO. ochraceaspecimens. Despite this limitation, it has been the basis for bio-inspired microphone designs for decades. Here, we present critical improvements to this classic hearing model based on information from three-dimensional reconstructions ofO. ochracea's tympanal organ. We identified the orientation of the tympana with respect to a frontal plane and the azimuthal angle segment between the tympana as morphological features essential to the flies' auditory acuity, and hypothesized a differentiated mechanical response to incoming sound on the ipsi- and contralateral sides that depend on these features. We incorporated spatially-varying model coefficients representing this asymmetric response, making a new quasi-two-dimensional (q2D) model. The q2D model has high accuracy (average errors of under 10%) for all incoming sound angles. This improved biomechanical model may inform the design of new microscale directional microphones and other small-scale acoustic sensor systems.

Frequency-specific, valveless flow control in insect-mimetic microfluidic devices.

Inexpensive, portable lab-on-a-chip devices would revolutionize fields like environmental monitoring and global health, but current microfluidic chips are tethered to extensive off-chip hardware. Insects, however, are self-contained and expertly manipulate fluids at the microscale using largely unexplored methods. We fabricated a series of microfluidic devices that mimic key features of insect respiratory kinematics observed by synchrotron-radiation imaging, including the collapse of portions of multiple respiratory tracts in response to a single fluctuating pressure signal. In one single-channel device, the flow rate and direction could be controlled by the actuation frequency alone, without the use of internal valves. Additionally, we fabricated multichannel chips whose individual channels responded selectively (on with a variable, frequency-dependent flow rate, or off) to a single, global actuation frequency. Our results demonstrate that insect-mimetic designs have the potential to drastically reduce the actuation overhead for microfluidic chips, and that insect respiratory systems may share features with impedance-mismatch pumps.

Effects of coral colony morphology on turbulent flow dynamics.

Local flow dynamics play a central role in physiological processes like respiration and nutrient uptake in coral reefs. Despite the importance of corals as hosts to a quarter of all marine life, and the pervasive threats facing corals, characterizing the hydrodynamics between the branches of scleractinian corals has remained a significant challenge. Here, we investigate the effects of colony branch density and surface structure on the local flow field using three-dimensional immersed boundary, large-eddy simulations for four different colony geometries under unidirectional oncoming flow conditions. The first two colonies were from the Pocillopora genus, one with a densely branched geometry, and one with a comparatively loosely branched geometry. The second pair of geometries were derived from a scan of a single Montipora capitata colony, one with the roughness elements called verrucae covering the surface intact, and one with the verrucae removed. For the Pocillopora corals, we found that the mean velocity profiles changed substantially in the center of the dense colony, becoming significantly reduced at middle heights where flow penetration was poor, while the mean velocity profiles in the loosely branched colony remained similar in character from the front to the back of the colony. For the Montipora corals, somewhat counterintuitively, the colony without verrucae produced almost double the maximum Reynolds stress magnitude above the colony compared to the colony without verrucae. This implies that the smooth colony will have enhanced mass transport and higher bed shear stress and friction velocity values relative to the colony with verrucae.

Selective pumping in a network: insect-style microscale flow transport.

A new paradigm for selective pumping of fluids in a complex network of channels in the microscale flow regime is presented. The model is inspired by internal flow distributions produced by the rhythmic wall contractions observed in many insect tracheal networks. The approach presented here is a natural extension of previous two-dimensional modeling of insect-inspired microscale flow transport in a single channel, and aims to manipulate fluids efficiently in microscale networks without the use of any mechanical valves. This selective pumping approach enables fluids to be transported, controlled and precisely directed into a specific branch in a network while avoiding other possible routes. In order to present a quantitative analysis of the selective pumping approach presented here, the velocity and pressure fields and the time-averaged net flow that are induced by prescribed wall contractions are calculated numerically using the method of fundamental solutions. More specifically, the Stokeslets-meshfree method is used in this study to solve the Stokes equations that govern the flow motions in a network with moving wall contractions. The results presented here might help in understanding some features of the insect respiratory system function and guide efforts to fabricate novel microfluidic devices for flow transport and mixing, and targeted drug delivery applications.