Digital process control of multi-step assays on centrifugal platforms using high-low-high rotational-pulse triggered valving.

Due to their capability for comprehensive sample-to-answer automation, the interest in centrifugal microfluidic systems has greatly increased in industry and academia over the last quarter century. The main applications of these "Lab-on-a-Disc" (LoaD) platforms are in decentralised bioanalytical point-of-use / point-of-care testing. Due to the unidirectional and omnipresent nature of the centrifugal force, advanced flow control is key to coordinate multi-step / multi-reagent assay formats on the LoaD. Formerly, flow control was often achieved by capillary burst valves which require gradual increments of the spin speed of the system-innate spindle motor. Recent advanced introduced a flow control scheme called 'rotational pulse actuated valves'. In these valves the sequence of valve actuation is determined by the architecture of the disc while actuation is triggered by freely programmable upward spike (i.e. Low-High-Low (LHL)) in the rotational frequency. This paradigm shift from conventional 'analogue' burst valves to 'digital' pulsing significantly increases the number of sequential while also improving the overall robustness of flow control. In this work, we expand on these LHL valves by introducing High-Low-High (HLH) pulse-actuated (PA) valving which are actuated by 'downward' spike in the disc spin-rate. These HLH valves are particularly useful for high spin-rate operations such as centrifugation of blood. We introduce two different HLH architectures and then combine the most promising with LHL valves to implement the time-dependent liquid handling protocol underlying a common liver function test panel.

Development of a scatter correction technique for planar 99mTc-MAA imaging to improve accuracy in lung shunt fraction estimation.

PURPOSE: Prior to 90Y selective internal radiation therapy (SIRT) treatment, 99mTc-MAA scintigraphy imaging is used in the estimation of the lung shunt fraction (LSF). Planar imaging is recommended for determining a LSF ratio. However, the estimate may be affected by scatter contributions, attenuation and respiratory motion. The objective of this study was to correct for the effects of scatter in the LSF, towards the determination of a more accurate estimation method of LSF derived from planar scintigraphy imaging, which is recommended by international guidelines. METHODS: The open access SIMIND Monte Carlo modelling software was used to estimate an optimum scatter window (SW) for scatter correction. The uncertainties associated with scatter and scatter contributions from the liver on the LSF were evaluated using an anthropomorphic thorax phantom and a virtual Vox-Man phantom. A brief retrospective examination of patient scans and tumour location investigated the impact that the inclusion of the simulated scatter corrections had on the LSF estimation. RESULTS: The percentage overestimation of the manufacturer recommended method of LSF estimation was 192%. SW corrections improved the uncertainty to within 19% for the range of known LSFs. Similar findings were observed for our patient and tumour location studies. CONCLUSION: The incorporated scatter corrections can significantly improve the accuracy of the LSF estimation, thereby providing a robust gamma camera, patient and tumour depth specific correction which is easily implementable. This is supported by Monte Carlo, phantom and preliminary patient studies.

Increasing radiation exposure from computed tomography in liver transplant recipients over time.

OBJECTIVES: To evaluate changes in radiation exposure from computed tomography (CT) among patients undergoing liver transplantation in our unit over a 10-year period. METHODS: We evaluated 134 elective patients, without hepatocellular carcinoma or cholangiocarcinoma who underwent transplantation in 2007-2008 and 2017-2018. CT scans performed in our hospital up to 2 years pre transplant and 1 year post transplant were evaluated. RESULTS: There was an increase in mean estimated effective radiation dose per patient in 2017-2018 compared to 2007-2008 (77.8 mSv ± 6.2 vs 56.7 mSv ± 5.9, p < 0.05). This change was mainly due to an increased number of pre-transplant CT scans per patient (2.9 ± 0.3 vs 1.4 ± 0.14, p = 0.0001). High radiation dose scan protocols were more frequently used in 2017-2018, with 4-phase liver CT accounting for a larger proportion of scans both pre-transplant (61% vs 43%, p = 0.004) and post-transplant (29% vs 13%, p = 0.002). A greater proportion of patients were exposed to > 100 mSv of ionising radiation in the 2017-2018 patients (29% vs 11%, p < 0.01). These figures are likely to be a significant under-estimate as they exclude other imaging modalities and CT scans performed at other institutions. CONCLUSION: Radiation exposure from diagnostic imaging has increased among liver transplant recipients at our institution over the last decade. This appears to be due to an increase in the number of CT scans performed, and a shift towards higher dose scan protocols.

A portable optical reader and wall projector towards enumeration of bio-conjugated beads or cells.

Measurement of the height of a packed column of cells or beads, which can be direclty related to the number of cells or beads present in a chamber, is an important step in a number of diagnostic assays. For example, haematocrit measurements may rapidly identify anemia or polycthemia. Recently, user-friendly and cost-efficient Lab-on-a-Chip devices have been developed towards isolating and counting cell sub-populations for diagnostic purposes. In this work, we present a low-cost optical module for estimating the filling level of packed magnetic beads within a Lab-on-a-Chip device. The module is compatible with a previously introduced, disposable microfluidic chip for rapid determination of CD4+ cell counts. The device is a simple optical microscope module is manufactured by 3D printing. An objective lens directly interrogates the height of packed beads which are efficiently isolated on the finger-actuated chip. Optionally, an inexpensive, battery-powered Light Emitting Diode may project a shadow of the microfluidic chip at approximately 50-fold magnification onto a nearby surface. The reader is calibrated with the filling levels of known concentrations of paramagnetic beads within the finger actuated chip. Results in direct and projector mode are compared to measurements from a conventional, inverted white-light microscope. All three read-out methods indicate a maximum variation of 6.5% between methods.