ORCID Profile
0000-0002-1461-229X
Current Organisation
Monash University
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Fluidisation and Fluid Mechanics | Interdisciplinary Engineering | Fluid mechanics and thermal engineering | Biomedical fluid mechanics | Microfluidics and nanofluidics | Biomedical Instrumentation | Computational Fluid Dynamics | Animal developmental and reproductive biology | Reproduction |
Expanding Knowledge in Engineering | Expanding Knowledge in the Physical Sciences | Scientific Instruments | Expanding Knowledge in the Biological Sciences |
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0LC01182G
Abstract: A 3D-structured sperm selection device is presented that achieves both high selectivity and high yield via thousands of parallel channels. The device significantly outperforms the best clinical practice by selecting ∼100 000 of higher-quality sperm.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6LC00490C
Abstract: Highly motile sperm with high DNA integrity can be selected based on their preference to turn corners. The result is a microfluidic device that passively collects sperm with high DNA integrity with the aim of improving the success rates of assisted reproduction.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 29-11-2021
Publisher: American Scientific Publishers
Date: 12-2012
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3LC51254A
Abstract: Sperm selection is essential to assisted reproductive technology (ART), influencing treatment outcomes and the health of offspring. The fundamental challenge of sperm selection is dictated by biology: a heterogeneous population of ~10(8) sperm per milliliter with a short lifetime in vitro. However, conventional sperm selection approaches result in less than 50% improvement in DNA integrity. Here, a clinically applicable microfluidic device is presented that selects sperm based on the progressive motility in 500 parallel microchannels. The result is a one-step procedure for semen purification and high DNA integrity sperm selection from 1 mL of raw semen in under 20 minutes. Experiments with bull sperm indicate more than 89% improvement in selected sperm vitality. Clinical tests with human sperm show more than 80% improvement in human DNA integrity, significantly outperforming the best current practices. These results demonstrate the presence of a sub-population of sperm with nearly intact chromatin and DNA integrity, and a simple clinically-applicable lab-on-a-chip method to select this population.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1LC01144H
Abstract: This perspective provides an overview of microfluidics for fertility efforts with a particular focus on clinical applications and commercialization.
Publisher: AIP Publishing
Date: 07-2015
DOI: 10.1063/1.4928129
Publisher: Wiley
Date: 09-02-2022
Abstract: Sperm swim through the female reproductive tract by propagating a 3D flagellar wave that is self‐regulatory in nature and driven by dynein motors. Traditional microscopy methods fail to capture the full dynamics of sperm flagellar activity as they only image and analyze sperm motility in 2D. Here, an automated platform to analyze sperm swimming behavior in 3D by using thin‐lens approximation and high‐speed dark field microscopy to reconstruct the flagellar waveform in 3D is presented. It is found that head‐tethered mouse sperm exhibit a rolling beating behavior in 3D with the beating frequency of 6.2 Hz using spectral analysis. The flagellar waveform bends in 3D, particularly in the distal regions, but is only weakly nonplanar and ambidextrous in nature, with the local helicity along the flagellum fluctuating between clockwise and counterclockwise handedness. These findings suggest a nonpersistent flagellar helicity. This method provides new opportunities for the accurate measurement of the full motion of eukaryotic flagella and cilia which is essential for a biophysical understanding of their activation by dynein motors.
Publisher: Oxford University Press (OUP)
Date: 03-2016
DOI: 10.1373/CLINCHEM.2015.250282
Abstract: More than 70 million couples worldwide are affected by infertility, with male-factor infertility accounting for about half of the cases. Semen analysis is critical for determining male fertility potential, but conventional testing is costly and complex. Here, we demonstrate a paper-based microfluidic approach to quantify male fertility potential, simultaneously measuring 3 critical semen parameters in 10 min: live and motile sperm concentrations and sperm motility. The device measures the colorimetric change of yellow tetrazolium dye to purple formazan by the diaphorase flavoprotein enzyme present in metabolically active human sperm to quantify live and motile sperm concentration. Sperm motility was determined as the ratio of motile to live sperm. We assessed the performance of the device by use of clinical semen s les, in parallel with standard clinical approaches. Detection limits of 8.46 and 15.18 million/mL were achieved for live and motile sperm concentrations, respectively. The live and motile sperm concentrations and motility values from our device correlated with those of the standard clinical approaches (R2 ≥ 0.84). In all cases, our device provided 100% agreement in terms of clinical outcome. The device was also robust and could tolerate conditions of high absolute humidity (22.8 g/m3) up to 16 weeks when packaged with desiccant. Our device outperforms existing commercial paper-based assays by quantitatively measuring live and motile sperm concentrations and motility, in only 10 min. This approach is applicable to current clinical practices as well as self-diagnostic applications.
Publisher: Wiley
Date: 04-12-2017
Abstract: Magnetotactic bacteria (MTB) play an important role in Earth's biogeochemical cycles by transporting minerals in aquatic ecosystems, and have shown promise for controlled transport of microscale objects in flow conditions. However, how MTB traverse complex flow environments is not clear. Here, using microfluidics and high-speed imaging, it is revealed that magnetotaxis enables directed motion of Magnetospirillum magneticum over long distances in flow velocities ranging from 2 to 1260 µm s
Publisher: eLife Sciences Publications, Ltd
Date: 03-2021
Publisher: Wiley
Date: 15-08-2022
Abstract: Infertility is a growing global health concern, with male factor infertility contributing to half of all cases. Semen analysis is crucial to infertility diagnostics. However, sperm morphology assessment, as a routine part of analysis, is still performed manually and is thus highly subjective. Here, a stacked ensemble of convolutional neural networks (CNNs) is presented for automated classification of human sperm head morphology. By combining traditional CNN models with modern residual and densely connected architectures using a multi‐class meta‐classifier, classification rate improvements of 2.7% (to 98.2%) and 2.3% (to 63.3%) on the HuSHeM and SCIAN‐MorphoSpermGS (SCIAN) datasets, respectively, are achieved. This considerable improvement in prediction performance is achieved as the meta‐classifier improves upon the in idual classification rates of the base models by ≈8.5%. The ensembled deep learning model is a powerful step toward an automated sperm morphology analysis, providing new opportunities to standardize clinical practice and reduce treatment costs to improve patient treatment.
Publisher: Research Square Platform LLC
Date: 16-09-2022
DOI: 10.21203/RS.3.RS-1993459/V1
Abstract: Sperm Selection is an essential component of all Assisted Reproductive Treatments (ART), and is by far and large the most neglected step in the ART workflow when it comes to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies and levels of DNA integrity Gold-standard techniques Density Gradient Centrifugation (DGC) and Swim Up (SU) have been proven to induce DNA fragmentation through the introduction of reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey towards selection. Sperm are first selected based on their motility and boundary following behavior, then on their expression of apoptotic markers, yielding over 68% more motile sperm than previously reported methods within a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results demonstrate an easy-to-use platform for sperm selection mimicking the biological function of the female reproductive tract during conception.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3AN00564J
Abstract: An automated analysis method for the sperm chromatin dispersion assay is demonstrated that quantifies DNA quality of more than 1000 of sperm at the single-cell and population levels within 7 minutes – a 40-fold reduction in processing time.
Publisher: ASMEDC
Date: 2011
Abstract: In the present paper a new model is proposed for electric double layer (EDL) overlapped in nanochannels. The model aimed to obtain a deeper insight of transport phenomena in nanoscale. Two-dimensional Nernst and ionic conservation equations are used to obtain electroosmotic potential distribution in flow field. In the proposed study, transport equations for flow, ionic concentration and electroosmotic potential are solved numerically via finite volume method. Moreover, Debye-Hu¨ckle (DH) approximation and symmetry condition, which limit the application, are avoided. Thus, the present model is suitable for prediction of electroosmotic flows through nanochannels as well as complicated asymmetric geometries with large nonuniform zeta potential distribution. For homogeneous zeta potential distribution, it has been shown that by reduction of channel height to values comparable with EDL thickness, Poisson-Boltzmann model produces inaccurate results and must be avoided. Furthermore, for overlapped electric double layer in nanochannels with heterogeneous zeta potential distribution it has been found that the present model returns modified ionic concentration and electroosmotic potential distribution compare to previous EDL overlapped models due to 2D solution of ionic concentration distribution. Finally, velocity profiles in EDL overlapped nanochannels are investigated and it has been showed that for pure electroosmotic flow the velocity profile deviates from the expected plug-like profile towards a parabolic profile.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2LC00803C
Abstract: We developed a device utilising acoustic streaming to drive a tuneable, well-regulated continuous flow in a microfluidic channel with suitable velocity range for probing sperm rheotaxis behaviour.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0LC00457J
Abstract: We presented an automated option for motility-based sperm selection with the potential to sort based on morphology with surface acoustic wave microfluidics.
Publisher: AIP Publishing
Date: 07-2018
DOI: 10.1063/1.5045672
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0LC00874E
Abstract: The FertDish features a clinically applicable sperm processing format, and enables high recovery of motile sperm with high DNA quality.
Publisher: eLife Sciences Publications, Ltd
Date: 30-04-2021
DOI: 10.7554/ELIFE.62524
Abstract: We demonstrate a technique for investigating the energetics of flagella or cilia. We record the planar beating of tethered mouse sperm at high resolution. Beating waveforms are reconstructed using proper orthogonal decomposition of the centerline tangent-angle profiles. Energy conservation is employed to obtain the mechanical power exerted by the dynein motors from the observed kinematics. A large proportion of the mechanical power exerted by the dynein motors is dissipated internally by the motors themselves. There could also be significant dissipation within the passive structures of the flagellum. The total internal dissipation is considerably greater than the hydrodynamic dissipation in the aqueous medium outside. The net power input from the dynein motors in sperm from Crisp2 -knockout mice is significantly smaller than in wildtype s les, indicating that ion-channel regulation by cysteine-rich secretory proteins controls energy flows powering the axoneme.
Publisher: Elsevier BV
Date: 09-2011
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6AY01506A
Abstract: A comprehensive paper-based assay for sperm chromatin integrity analysis has been demonstrated that quantifies both DNA fragmentation and packaging.
Publisher: Wiley
Date: 04-03-2022
Abstract: Selection of high‐quality sperm is crucial to assisted reproduction. However, conventional clinical methods for sperm selection are manual and prone to operator errors. This article presents ‘sperm syringe', a scalable technology that mimics the highly parallelized 3D selection process in vivo via a 3D network of 560 microchannels to select high‐quality sperm. Sperm syringe retrieves more than 41% of healthy sperm from the initial sperm s le in under 15 min, providing a sufficient volume (≈500 µL) and number (1,600,000) of high‐quality sperm for fertility treatments. Experiments with bull and human sperm indicate 65% improvement in selected sperm morphology and DNA integrity, considerably outperforming the current best clinical practices. This approach enables the selection of a subpopulation of high‐quality human sperm from an oligozoospermia s le with DNA integrity below the reference value for fertility. The fabrication method of the device is also simple and scalable, representing a commercially viable technology for translation and clinical adoption. Sperm syringe provides a promising opportunity for clinics to use less invasive assisted reproductive technologies (ARTs) over intracytoplasmic sperm injection, thus reducing the associated clinical workload and optimizing long‐term health outcomes for ART‐conceived children.
Publisher: American Scientific Publishers
Date: 12-2011
Publisher: Springer Science and Business Media LLC
Date: 06-05-2023
DOI: 10.1038/S42003-023-04875-2
Abstract: 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. Sperm groups benefit from higher swimming velocity, exceeding that of in idual sperm by over 50%. We find that sperm associated with a group possess high DNA integrity (7% fragmentation index) – a stark contrast to in idual sperm exhibiting low DNA integrity ( 50% fragmentation index) – and feature membrane decapacitation factors that mediate sperm attachment to form the group. Cooperative behaviour becomes less prevalent upon capacitation and groups tend to disband as the surrounding viscosity reduces. When sperm from different male sources are present, related sperm preferentially form groups and achieve greater swimming velocity, while unrelated sperm are slowed by their involvement in a group. These findings reveal cooperation as a selective mode of human sperm motion – sperm with high DNA integrity cooperate to transit the highly viscous regions in the female tract and outcompete rival sperm for fertilization – and provide insight into cooperation-based sperm selection strategies for assisted reproduction.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2015
DOI: 10.1038/NCOMMS9703
Abstract: Sperm motion near surfaces plays a crucial role in fertilization, but the nature of this motion has not been resolved. Using total internal reflection fluorescence microscopy, we selectively imaged motile human and bull sperm located within one micron of a surface, revealing a distinct two-dimensional (2D) ‘slither’ swimming mode whereby the full cell length (50–80 μm) is confined within 1 μm of a surface. This behaviour is distinct from bulk and near-wall swimming modes where the flagellar wave is helical and the head continuously rotates. The slither mode is intermittent (∼1 s, ∼70 μm), and in human sperm, is observed only for viscosities over 20 mPa·s. Bull sperm are slower in this surface-confined swimming mode, owing to a decrease in their flagellar wave litude. In contrast, human sperm are ∼50% faster—suggesting a strategy that is well suited to the highly viscous and confined lumen within the human fallopian tube.
Publisher: AIP Publishing
Date: 2018
DOI: 10.1063/1.5024508
Abstract: Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250 μm s−1. Our findings bring new insights into the migration behaviour of MTB in their natural habitats and their potential in vivo applications as microbiorobots.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2021
DOI: 10.1038/S41467-021-23773-X
Abstract: The fallopian tube is lined with a highly complex folded epithelium surrounding a lumen that progressively narrows. To study the influence of this labyrinthine complexity on sperm behavior, we use droplet microfluidics to create soft curved interfaces over a range of curvatures corresponding to the in vivo environment. We reveal a dynamic response mechanism in sperm, switching from a progressive surface-aligned motility mode at low curvatures (larger droplets), to an aggressive surface-attacking mode at high curvatures (smaller droplets of µm-radius). We show that sperm in the attacking mode swim ~33% slower, spend 1.66-fold longer at the interface and have a 66% lower beating litude than in the progressive mode. These findings demonstrate that surface curvature within the fallopian tube alters sperm motion from a faster surface aligned locomotion in distal regions to a prolonged physical contact with the epithelium near the site of fertilization, the latter being known to promote capacitation and fertilization competence.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2023
DOI: 10.1038/S41378-023-00501-7
Abstract: Sperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen ( n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.
Publisher: Elsevier BV
Date: 2011
Publisher: American Chemical Society (ACS)
Date: 20-10-2015
DOI: 10.1021/JACS.5B08523
Abstract: DNA analysis is essential for diagnosis and monitoring of many diseases. Conventional DNA testing is generally limited to the laboratory. Increasing access to relevant technologies can improve patient care and outcomes in both developed and developing regions. Here, we demonstrate direct DNA analysis in paper-based devices, uniquely enabled by ion concentration polarization at the interface of patterned nanoporous membranes in paper (paper-based ICP). Hepatitis B virus DNA targets in human serum are simultaneously preconcentrated, separated, and detected in a single 10 min operation. A limit of detection of 150 copies/mL is achieved without prior viral load lification, sufficient for early diagnosis of hepatitis B. We clinically assess the DNA integrity of sperm cells in raw human semen s les. The percent DNA fragmentation results from the paper-based ICP devices strongly correlate (R(2) = 0.98) with the sperm chromatin structure assay. In all cases, agreement was 100% with respect to the clinical decision. Paper-based ICP can provide inexpensive and accessible advanced molecular diagnostics.
Publisher: American Chemical Society (ACS)
Date: 22-05-2020
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 17-05-2021
DOI: 10.1038/S41585-021-00465-1
Abstract: 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%. Machine learning, an automated method of data analysis based on patterns and inference, is increasingly being deployed within the health-care sector to improve diagnostics and therapeutics. This technique is already aiding embryo selection in some fertility clinics, and has also been applied in research laboratories to improve sperm analysis and selection. Tremendous opportunities exist for machine learning to advance male fertility treatments. The fundamental challenge of sperm selection - selecting the most promising candidate from 10
Publisher: Elsevier BV
Date: 12-2010
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2LC01190E
Abstract: A microfluidic chip capable of separating 16 000 motile sperm with high DNA integrity using rheotaxis activated by boomerang-shaped microchannels.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2016
DOI: 10.1038/SREP26669
Abstract: Sperm migration through the female tract is crucial to fertilization, but the role of the complex and confined structure of the fallopian tube in sperm guidance remains unknown. Here, by confocal imaging microchannels head-on, we distinguish corner- vs. wall- vs. bulk-swimming bull sperm in confined geometries. Corner-swimming dominates with local areal concentrations as high as 200-fold that of the bulk. The relative degree of corner-swimming is strongest in small channels, decreases with increasing channel size and plateaus for channels above 200 μm. Corner-swimming remains predominant across the physiologically-relevant range of viscosity and pH. Together, boundary-following sperm account for over 95% of the sperm distribution in small rectangular channels, which is similar to the percentage of wall swimmers in circular channels of similar size. We also demonstrate that wall-swimming sperm travel closer to walls in smaller channels (~100 μm), where the opposite wall is within the hydrodynamic interaction length-scale. The corner accumulation effect is more than the superposition of the influence of two walls and over 5-fold stronger than that of a single wall. These findings suggest that folds and corners are dominant in sperm migration in the narrow (sub-mm) lumen of the fallopian tube and microchannel-based sperm selection devices.
Start Date: 2023
End Date: 2023
Amount: $425,963.00
Funder: Australian Research Council
View Funded ActivityStart Date: 02-2021
End Date: 12-2024
Amount: $344,301.00
Funder: Australian Research Council
View Funded ActivityStart Date: 05-2019
End Date: 10-2023
Amount: $460,000.00
Funder: Australian Research Council
View Funded Activity