97 research outputs found
A quantum heat exchanger for nanotechnology
In this paper, we design a quantum heat exchanger which converts heat into light on relatively short quantum optical time scales. Our scheme takes advantage of heat transfer as well as collective cavity-mediated laser cooling of an atomic gas inside a cavitating bubble. Laser cooling routinely transfers individually trapped ions to nano-Kelvin temperatures for applications in quantum technology. The quantum heat exchanger which we propose here might be able to provide cooling rates of the order of Kelvin temperatures per millisecond and is expected to find applications in micro- and nanotechnology
A review on impedimetric immunosensors for pathogen and biomarker detection
Since the discovery of antibiotics in the first quarter of the twentieth century, their use has been the principal approach to treat bacterial infection. Modernized medicine such as cancer therapy, organ transplantation or advanced major surgeries require effective antibiotics to manage bacterial infections. However, the irresponsible use of antibiotics along with the lack of development has led to the emergence of antimicrobial resistance which is considered a serious global threat due to the rise of multidrug-resistant bacteria (Wang et al. in Antibiotic resistance: a rundown of a global crisis, pp. 1645ā1658, 2018). Currently employed diagnostics techniques are microscopy, colony counting, ELISA, PCR, RT-PCR, surface-enhanced Raman scattering and others. These techniques provide satisfactory selectivity and sensitivity (Joung et al. in Sens Actuators B Chem 161:824ā831, 2012). Nevertheless, they demand specialized personnel and expensive and sophisticated machinery which can be labour-intensive and time-consuming, (Malvano et al. in Sensors (Switzerland) 18:1ā11, 2018; Mantzila et al. in Anal Chem 80:1169ā1175, 2008). To get around these problems, new technologies such as biosensing and lab-on-a-chip devices have emerged in the last two decades. Impedimetric immunosensors function by applying electrochemical impedance spectroscopy to a biosensor platform using antibodies or other affinity proteins such as Affimers (Tiede et al. in Elife 6(c):1ā35, 2017) or other binding proteins (Weiss et al. in Electrochim Acta 50:4248ā4256, 2005) as bioreceptors, which provide excellent sensitivity and selectivity. Pre-enrichment steps are not required and this allows miniaturization and low-cost. In this review different types of impedimetric immunosensors are reported according to the type of electrode and their base layer materials, either self-assembled monolayers or polymeric layers, composition and functionalization for different types of bacteria, viruses, fungi and disease biomarkers. Additionally, novel protein scaffolds, both antibody derived and non-antibody derived, used to specifically target the analyte are considered
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The generation of multi-laminar reagent streams for rapid, sequential (bio)chemical reactions on magnetic particles in a continuous flow microreactor
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.We demonstrate a versatile microfluidic system for performing rapid, consecutive (bio)chemical reactions in continuous flow. Surface-functionalised magnetic microparticles are introduced into a chamber
and pulled, via a magnet, across a series of laminar flow streams containing different reagents, thus performing multiple sequential reactions on the particlesā surface. Such a continuous flow method eliminates many of the inefficiencies associated with batch techniques, such as the time-consuming, laborious sequential reaction and washing steps, to yield a system that can perform analyses far more rapidly and with less reagent volume than conventional methods. This innovative device has been applied to a two-reaction step mouse IgG sandwich immunoassay and one- and two-reaction step DNA hybridisation assays, all of which were completed within one minute. These results pave the way for a multi-purpose microreactor that can perform a variety of analytical and synthetic processes.This study is funded by the Engineering and Physical Sciences Research Council (EPSRC)
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Temperature-based tuning of magnetic particle separation by on-chip free-flow magnetophoresis
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.Free-flow magnetophoresis provides a fast and efficient means of continuous flow magnetic separation for the detection of biological analytes, due to the wide variety of magnetic particle surface properties available for binding specific targets. Here, we investigate the effect of temperature changes on the deflection behaviour of magnetic particles in a microfluidic magnetophoresis separation chamber. It was found that the extent of deflection was greatly increased at higher temperatures due to decreased solution
viscosity and thus reduced resistance against particle motion. This concept was used to improve the resolution of the separation of 2.8 Ī¼m and 1 Ī¼m diameter magnetic particles. Hence, controlling the
temperature of the separation system provides a simple but highly effective means of enhancing magnetic separation efficiency. This concept could also be applied to the temperature-based tuning of microparticle
trajectories in many others types of continuous flow processes, such as those using optical, electrical or acoustic forces.This study is funded by the Engineering and Physical Sciences Research Council (EPSRC)
On-chip production of nanometer sized 'Ultra fine' bubble populations
Microbubble (MB) contrast agents have been used for many years as image enhancers for medical Ultrasound (US). Ultra-Fine bubble (UFB) populations of bubbles <1 Āµm in diameter are a relatively new technology that has found use as highly effective āecoā cleaning agents. High-resolution US imaging is another potentially exciting area for UFB. This paper reports the on-chip production of UFB populations with a diameter of ~ 500 ā 700 nm at a concentration of 10Ā¹ā° bub / mL. These UFB showed US scattering at higher frequency fields and enhanced contrast when imaging in in vivo mouse models
Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles
Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body. However, many new therapeutics exhibit poor water solubility or stability, which has led to the requirement for the development of effective hydrophobic drug delivery systems. This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted, triggered drug release. This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gasāaqueous interfaces. Oil layer inside microbubbles were produced with diameters of 2.4Ā±0.3āĪ¼m (s.d., 1.6āĪ¼m) and at concentrations up to 106 bubbles per milliliter. The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements, quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging
The influence of intercalating perfluorohexane into lipid shells on nano and microbubble stability
Microbubbles are potential diagnostic and therapeutic agents. In vivo stability is important as the bubbles are required to survive multiple passages through the heart and lungs to allow targeting and delivery. Here we have systematically varied key parameters affecting microbubble lifetime to significantly increase in vivo stability. Whilst shell and core composition are found to have an important role in improving microbubble stability, we show that inclusion of small quantities of C6F14 in the microbubble bolus significantly improves microbubble lifetime. Our results indicate that C6F14 inserts into the lipid shell, decreasing surface tension to 19 mN m-1, and increasing shell resistance, in addition to saturating the surrounding medium. Surface area isotherms suggest that C6F14 incorporates into the acyl chain region of the lipid at a high molar ratio, indicating ā¼2 perfluorocarbon molecules per 5 lipid molecules. The resulting microbubble boluses exhibit a higher in vivo image intensity compared to commercial compositions, as well as longer lifetimes
Nested-Nanobubbles for Ultrasound Triggered Drug Release
Due to their size (1-10 Ī¼m) microbubble-based drug delivery agents suffer from confinement to the vasculature, limiting tumour penetration and potentially reducing drug efficacy. Nanobubbles (NBs) have emerged as promising candidates for ultrasound triggered drug delivery, due to their small size allowing drug delivery complexes to take advantage of the enhanced permeability and retention effect. In this study we describe a simple method for production of Nested-NBs, by encapsulation of NBs (~ 100 nm) within drug loaded liposomes. This method combines the efficient and well-established drug loading capabilities of liposomes, whilst utilizing NBs as an acoustic trigger for drug release. Encapsulation was characterized using Transmission Electron Microscopy with an encapsulation efficiency of 22 Ā± 2 %. Nested-NBs demonstrated echogenicity using diagnostic B-mode imaging and acoustic emissions were monitored during high intensity focused ultrasound (HIFU) in addition to monitoring of model drug release. Results showed that although the encapsulated NBs were destroyed by pulsed HIFU (peak negative pressure 1.54 ā 4.83 MPa), signified by loss of echogenicity and detection of inertial cavitation, no model drug release was observed. Changing modality to continuous wave (CW) HIFU produced release across a range of peak negative pressures (2.01 ā 3.90 MPa), likely due to a synergistic effect of mechanical and increased thermal stimuli. Due to this, we predict that our NBs contain a mixed population of both gaseous and liquid core particles, which upon CW HIFU undergo rapid phase conversion, triggering liposomal drug release. This hypothesis was investigated using previously described models to predict the existence of droplets and their phase change potential and the ability of this phase change to induce liposomal drug release
Tumour associated vasculature-on-a-chip for the evaluation of microbubble-mediated delivery of targeted liposomes
The vascular system is the primary route for the delivery of therapeutic drugs throughout the body and is an important barrier at the region of disease interest, such as a solid tumour. The development of complex 3D tumour cultures has progressed significantly in recent years however, the generation of perfusable vascularised tumour models still presents many challenges. This study presents a microfluidic-based vasculature system that can be induced to display properties of tumour-associated blood vessels without direct incorporation of tumour cells. Conditioning healthy endothelialāfibroblast cell vasculature co-cultures with media taken from tumour cell cultures was found to result in the formation of disorganised, tortuous networks which display characteristics consistent with those of tumour-associated vasculature. Integrin Ī±vĪ²3, a cell adhesion receptor associated with angiogenesis, was found to be upregulated in vasculature co-cultures conditioned with tumour cell media (TCM) ā consistent with the reported Ī±vĪ²3 expression pattern in angiogenic tumour vasculature in vivo. Increased accumulation of liposomes (LSs) conjugated to antibodies against Ī±vĪ²3 was observed in TCM networks compared to non-conditioned networks, indicating Ī±vĪ²3 may be a potential target for the delivery of drugs specifically to tumour vasculature. Furthermore, the use of microbubbles (MBs) and ultrasound (US) to further enhance the delivery of LSs to TCM-conditioned vasculature was investigated. Quantification of fluorescent LS accumulation post-perfusion of the vascular network showed 3-fold increased accumulation with the use of MBs and US, suggesting that targeted LS delivery could be further improved with the use of locally administered MBs and US
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