A deep sea lab on a chip chemical sensor

The measurement of chemical concentrations within the oceans is crucial for our understanding of its biogeochemical processes. Such data is vital for; studies of climate and environment change; natural resource management; assessment of pollution, human impact and biodiversity. Current measurement methods (sampling and large in situ instrumentation) cannot provide the quantity and quality of biogeochemical data that is required. The factors limiting the widespread collection of quality data include, sample degradation/contamination, instrument size, cost and insufficient sensitivity.New technologies allow the manufacture of Lab On a Chip (L.O.C.) devices that can be used as small, low-cost and low power sensors. There are numerous demonstrations of these devices in the laboratory where it is possible to use standard bench top equipment to operate them. Within the National Oceanography Centre Southampton and the Nanoscale System Integration Research Group at Southampton University it has been proposed that integrated L.O.C. devices could be used autonomously and remotely in the marine environment. These innovative micro-devices could provide in situ real time synoptic data on processes with temporal and spatial scales smaller than currently sampled. This report details the development, laboratory testing and field trial of the world's first deep sea in situ L.O.C. chemical sensor. Preparatory work for the design of the next generation of marine L.O.C. devices including low-cost fabrication in fluoropolymer materials (which are naturally robust and chemically resistant) is also presented.The L.O.C. devices within this study use a reagent based colorimetric protocol to determine the concentration of a chemical within a sea-water sample. The optical absorption when the reagent is mixed with a sample is proportional to the chemical concentration and is measured using a double beam spectrophotometer. This method can be used in the metrology of a number of chemical species including nutrients and pollutants and therefore this technology is generic. The detection of nitrite and nitrate at a wavelength of 540nm is used as a proof of concept within this report. Nitrite samples are combined with α-napthylamine and sulphanilamide to form a coloured dye. The absorption of the dye is proportional to the nitrite concentration. Nitrate is reduced to nitrite using a cadmium column and then measured in same manner. The L.O.C. devices are fabricated using negative photolithography on photosensitive epoxy resin. Micro channels measuring 500 by 500 µm are used to create micromixers, optical detection paths and fluid delivery ports on a device with a footprint of 45 by 45 mm. The absorption is measured with low powered portable electronics, a modulated light emitting diode source and photodiode detector both coupled to polymer fibres. The mixer uses a three dimensional split and recombine technique to ensure effective mixing of the chemicals and sample.On the laboratory bench the sensor was capable of continuously sampling nitrite concentration levels in sea-water at 60?l/min with a limit of detection of 47.6nM and a precision of 89.3nM at 15µM. Once reconfigured it was capable of detecting nitrate in seawater, at the same flow rates with a limit of detection of 1.75µM and a precision of 9.26µM at 100µM. An in situ version of the sensor, packaged within a pressure compensated housing measuring Ø120mm by 300mm, was deployed in the mid-Atlantic. It provided key functionality and construction methodologies for future generation devices. These trials also identified the developments necessary for the sensor to work as efficiently at depths of 1500m as on the laboratory bench

The fabrication of lab-on-chip devices from fluoropolymers

Three different rapid manufacturing methods for the construction of fluoropolymer microfluidic devices were investigated: (1) fluoropolymer/epoxy laminate/fluoropolymer structures, (2) fluoropolymer/fluoropolymer structures and (3) fluoropolymer/epoxy laminate/glass structures. The structures are chemically and physically robust and the fluoropolymer constructs can be used for optical wave guiding. Principles behind the use of fluoropolymer waveguide constructs and a basic theoretical analysis of the improvements they offer are presented. The otherwise problematic bonding of the polymers was facilitated by chemical (sodium naphthalene) surface treatment. The effects of the process were characterized by contact angle and bond strength measurements. For demonstration purposes, microfluidic channels were fabricated using Ordyl SY epoxy laminate (methods 1 and 3) and hot embossing of the polymers (method 2). The first method (fluoropolymer/epoxy laminate/fluoropolymer) proved to be the most reliable and successful, in particular when bonding the various layers. (Some figures in this article are in colour only in the electronic version

Microsystem technology for marine measurment

peer reviewe

Early Video Assisted Thoracoscopic Surgery (VATS) or Intrapleural Enzyme Therapy (IET) in Pleural Infection – A Feasibility Randomized Controlled Trial (The Third Multicenter Intrapleural Sepsis Trial – MIST-3)

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery versus non-surgery trial as well as the key outcome measures which are important to identify relevant patient-centered outcomes in a RCT. Methods: MIST-3 was a prospective multicenter RCT. All-comers with a confirmed diagnosis of pleural infection were enrolled and those with ongoing pleural sepsis after up to 24-hours of standard care were randomized to one of 3 arms; continued standard care, IET, or surgical opinion for VATS. The analysis was by intention to treat, despite some participants in the VATS arm not being fit enough to undergo surgical intervention. Main Results: Of 97 eligible patients, 60 (62%) participants were randomized. Despite a difference in time-to-intervention, length of stay was similar in both arms. There were no significant inter-group differences in 2-month readmission and further intervention. Compared to VATS, IET demonstrated a greater improvement in mean EQ-5D-5L health utility index at 2 months from baseline. Conclusion: This is the first multicenter RCT of early IET vs early surgery in pleural infection. Despite logistical challenges posed by the COVID-19 pandemic, the study met its predefined feasibility criteria. Potential shortening of LOS with early surgery, and signals toward earlier resolution of pain and shortened recovery with IET were demonstrated. The study findings suggest that a definitive study is feasible and required to assess optimal initial management. Clinical trial registration available at www.isrctn.com, ID: ISRCTN18192121