High-throughput sperm DNA analysis at the single-cell and population levels.

Clinical semen quality assessment is critical to the treatment of infertility. Sperm DNA integrity testing provides critical information that can steer treatment and influence outcomes and offspring health. Flow cytometry is the gold standard approach to assess DNA integrity, but it is not commonly applied at the clinical level.

Human sperm cooperate to transit highly viscous regions on the competitive pathway to fertilization.

Human sperm compete for fertilization. Here, we find that human sperm, unexpectedly, cooperate under conditions mimicking the viscosity contrasts in the female reproductive tract. Sperm attach at the head region to migrate as a cooperative group upon transit into and through a high viscosity medium (15-100 cP) from low viscosity seminal fluid.

Rheological Behavior of Phase Change Slurries for Thermal Energy Applications.

Phase change materials that leverage the latent heat of solid-liquid transition have many applications in thermal energy transport and storage. When employed as particles within a carrier fluid, the resulting phase change slurries (PCSs) could outperform present-day single-phase working fluids─provided that viscous losses can be minimized. This work investigates the rheological behavior of encapsulated and nonencapsulated phase change slurries (PCSs) for applicability in flowing thermal energy systems.

Machine learning for sperm selection.

Infertility rates and the number of couples seeking fertility care have increased worldwide over the past few decades. Over 2.5 million cycles of assisted reproductive technologies are being performed globally every year, but the success rate has remained at ~33%.

Selection of high-quality sperm with thousands of parallel channels.

Sperm selection is essential for successful fertilization and embryo development. Current clinical sperm selection methods are labor-intensive and lack the selectivity required to isolate high-quality sperm. Microfluidic sperm selection approaches have shown promise but present a trade-off between the quality and quantity of selected sperm - clinicians demand both.

FertDish: microfluidic sperm selection-in-a-dish for intracytoplasmic sperm injection.

The selection of high quality sperm is critical for intracytoplasmic sperm injection (ICSI), a prevalent assisted reproduction technology. However, standard selection methods are time-consuming and fail to recover the most viable sperm, thereby limiting the ICSI success rate. Microfluidics enables rapid selection of viable sperm in a manner representing in vivo processes, however, existing platforms lack clinical applicability.

Exploring Anomalous Fluid Behavior at the Nanoscale: Direct Visualization and Quantification via Nanofluidic Devices.

Nanofluidics is the study of fluids under nanoscale confinement, where small-scale effects dictate fluid physics and continuum assumptions are no longer fully valid. At this scale, because of large surface-area-to-volume ratios, the fluid interaction with boundaries becomes more pronounced, and both short-range steric/hydration forces and long-range van der Waals forces and electrostatic forces dictate fluid behavior. These forces lead to a spectrum of anomalous transport and thermodynamic phenomena such as ultrafast water flow, enhanced ion transport, extreme phase transition temperatures, and slow biomolecule diffusion, which have been the subject of extensive computational studies.

When robotics met fluidics.

High-throughput fluidic technologies have increased the speed and accuracy of fluid processing to the extent that unlocking further gains will require replacing the human operator with a robotic counterpart. Recent advances in chemistry and biology, such as gene editing, have further exacerbated the need for smart, high-throughput experimentation. A growing number of innovations at the intersection of robotics and fluidics illustrate the tremendous opportunity in achieving fully self-driving fluid systems.

Prediction of DNA Integrity from Morphological Parameters Using a Single-Sperm DNA Fragmentation Index Assay.

Intracytoplasmic sperm injection is a popular form of in vitro fertilization, where single sperm are selected by a clinician and injected into an egg. Whereas clinicians employ general morphology-based guidelines to select the healthiest-looking sperm, it remains unclear to what extent an individual sperm's physical parameters correlate with the quality of internal DNA cargo-a measurement that cannot be obtained without first damaging the sperm. Herein, a single-cell DNA fragmentation index (DFI) assay is demonstrated, which combines the single-cell nature of the acridine orange test with the quantitative aspect of the sperm chromatin structure assay, to create a database of DFI-scored brightfield images.

Deep learning-based selection of human sperm with high DNA integrity.

Despite the importance of sperm DNA to human reproduction, currently no method exists to assess individual sperm DNA quality prior to clinical selection. Traditionally, skilled clinicians select sperm based on a variety of morphological and motility criteria, but without direct knowledge of their DNA cargo. Here, we show how a deep convolutional neural network can be trained on a collection of ~1000 sperm cells of known DNA quality, to predict DNA quality from brightfield images alone.

Two-dimensional planar swimming selects for high DNA integrity sperm.

Selection of high-quality sperm is critical to the success of assisted reproductive technologies. Clinical screening for top sperm has long focused on sperm swimming ability when following boundaries or when fully free of constraints. In this work, we demonstrate a sperm selection approach with parallel 2 μm tall confined selection channels that prohibit rotation of the sperm head and require planar swimming.

Deep Learning with Microfluidics for Biotechnology.

Advances in high-throughput and multiplexed microfluidics have rewarded biotechnology researchers with vast amounts of data but not necessarily the ability to analyze complex data effectively. Over the past few years, deep artificial neural networks (ANNs) leveraging modern graphics processing units (GPUs) have enabled the rapid analysis of structured input data - sequences, images, videos - to predict complex outputs with unprecedented accuracy. While there have been early successes in flow cytometry, for example, the extensive potential of pairing microfluidics (to acquire data) and deep learning (to analyze data) to tackle biotechnology challenges remains largely untapped.

Capillary Condensation in 8 nm Deep Channels.

Condensation on the nanoscale is essential to understand many natural and synthetic systems relevant to water, air, and energy. Despite its importance, the underlying physics of condensation initiation and propagation remain largely unknown at sub-10 nm, mainly due to the challenges of controlling and probing such small systems. Here we study the condensation of n-propane down to 8 nm confinement in a nanofluidic system, distinct from previous studies at ∼100 nm.

Microfluidics for sperm analysis and selection.

Infertility is a growing global health issue with far-reaching socioeconomic implications. A downward trend in male fertility highlights the acute need for affordable and accessible diagnosis and treatment. Assisted reproductive technologies are effective in treating male infertility, but their success rate has plateaued at ∼33% per cycle.

The Full Pressure-Temperature Phase Envelope of a Mixture in 1000 Microfluidic Chambers.

Knowing the thermodynamic state of complex mixtures-liquid, gas, supercritical or two-phase-is essential to industrial chemical processes. Traditionally, phase diagrams are compiled piecemeal from individual measurements in a pressure-volume-temperature cell performed in series, where each point is subject to a long fluid equilibrium time. Herein, 1000 microfluidic chambers, each isolated by a liquid piston and set to a different pressure and temperature combination, provide the complete pressure-temperature phase diagram of a hydrocarbon mixture at once, including the thermodynamic phase envelope.

Microfluidic and nanofluidic phase behaviour characterization for industrial CO, oil and gas.

Microfluidic systems that leverage unique micro-scale phenomena have been developed to provide rapid, accurate and robust analysis, predominantly for biomedical applications. These attributes, in addition to the ability to access high temperatures and pressures, have motivated recent expanded applications in phase measurements relevant to industrial CO, oil and gas applications. We here present a comprehensive review of this exciting new field, separating microfluidic and nanofluidic approaches.

Periodic harvesting of microalgae from calcium alginate hydrogels for sustained high-density production.

High-density biomass production is currently only realized in biofilm-based photobioreactors. Harvest yields of whole biofilms are self-limited by daughter-upon-parent cell growth that hinders light and leads to respiratory biomass losses. In this work, we demonstrate a sustainable multi-harvest approach for prolonged generation of high-density biomass.

Microfluidic Manufacturing of Polymeric Nanoparticles: Comparing Flow Control of Multiscale Structure in Single-Phase Staggered Herringbone and Two-Phase Reactors.

We compare the microfluidic manufacturing of polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles (NPs) in a single-phase staggered herringbone (SHB) mixer and in a two-phase gas-liquid segmented mixer. NPs generated from two different copolymer compositions in both reactors and at three different flow rates, along with NPs generated using a conventional bulk method, are compared with respect to morphologies, dimensions, and internal crystallinities. Our work, the first direct comparison between alternate microfluidic NP synthesis methods, shows three key findings: (i) NP morphologies and dimensions produced in the bulk are different from those produced in a microfluidic mixer, whereas NP crystallinities produced in the bulk and in the SHB mixer are similar; (ii) NP morphologies, dimensions, and crystallinities produced in the single-phase SHB and two-phase mixers at the lowest flow rate are similar; and (iii) NP morphologies, dimensions, and crystallinities change with flow rate in the two-phase mixer but not in the single-phase SHB mixer.

Direct Measurement of the Fluid Phase Diagram.

The thermodynamic phase of a fluid (liquid, vapor or supercritical) is fundamental to all chemical processes, and the critical point is particularly important for supercritical chemical extraction. Conventional phase measurement methods require hours to obtain a single datum on the pressure and temperature diagram. Here, we present the direct measurement of the full pressure-temperature phase diagram, with 10 000 microwells.

Breathable waveguides for combined light and CO2 delivery to microalgae.

Suboptimal light and chemical distribution (CO2, O2) in photobioreactors hinder phototrophic microalgal productivity and prevent economically scalable production of biofuels and bioproducts. Current strategies that improve illumination in reactors negatively impact chemical distribution, and vice versa. In this work, an integrated illumination and aeration approach is demonstrated using a gas-permeable planar waveguide that enables combined light and chemical distribution.

Self-assembled nanoparticle-stabilized photocatalytic reactors.

The efficiency of nanostructured photocatalysts continues to improve at an impressive pace and is closing in on those needed for commercial applications; however, present-day reactor strategies used to deploy these nanostructures fail to achieve the sufficient areas (>1 m(2)) needed for solar application. Here we report the Self-assembled Nanoparticle-stabilized Photocatalytic Reactor (SNPR), a fully-scalable reactor strategy comprised only of nanoparticles adsorbed at the fluid-fluid interfaces of oil-in-water emulsions, water-in-oil emulsions, and CO2-in-water foams. We show that SNPRs naturally disperse over open water and need no physical substrate, requiring only photocatalysts and fluid.

Microalgae on display: a microfluidic pixel-based irradiance assay for photosynthetic growth.

Microalgal biofuel is an emerging sustainable energy resource. Photosynthetic growth is heavily dependent on irradiance, therefore photobioreactor design optimization requires comprehensive screening of irradiance variables, such as intensity, time variance and spectral composition. Here we present a microfluidic irradiance assay which leverages liquid crystal display technology to provide multiplexed screening of irradiance conditions on growth.

Fast fluorescence-based microfluidic method for measuring minimum miscibility pressure of CO2 in crude oils.

Carbon capture, storage, and utilization has emerged as an essential technology for near-term CO2 emission control. The largest CO2 projects globally combine storage and oil recovery. The efficiency of this process relies critically on the miscibility of CO2 in crude oils at reservoir conditions.

Quantifying the volume of single cells continuously using a microfluidic pressure-driven trap with media exchange.

We demonstrate a microfluidic device capable of tracking the volume of individual cells by integrating an on-chip volume sensor with pressure-activated cell trapping capabilities. The device creates a dynamic trap by operating in feedback; a cell is periodically redirected back and forth through a microfluidic volume sensor (Coulter principle). Sieve valves are positioned on both ends of the sensing channel, creating a physical barrier which enables media to be quickly exchanged while keeping a cell firmly in place.