Probing Micro-dynamics with Optical Tweezers: Pendula, Cell-stretching, and Thermodynamic Fluctuations

Optical tweezers are a powerful experimental tool, commonly utilised in microscopic experiments in a diverse cross-section of scientific fields, from biophysics to hydrodynamics of small systems, by enabling the exertion and measurement of forces that act in microscopic soft-matter systems. This thesis documents three experiments that probe the micro-dynamics of such systems. First the theory of the mechanical phenomenon of the Kapitza pendulum is described: the unusual behaviour of the equilibrium of a pendulum whose point of suspension undergoes high frequency vertical oscillations. To go beyond this case, a Kapitza pendulum in the presence of significant damping is considered. Theoretical calculations are presented, revealing new regimes and positions of dynamic equilibrium. These are supported by Brownian motion simulations. A microscopic optical analogue of the damped Kapitza pendulum is realised using optical tweezers and the results of the theory and simulations are confirmed experimentally. Next, the condition of diabetic retinopathy within sufferers of diabetes mellitus is discussed with reference to the deformability of red blood cells. A pilot study is conducted to assess the viability of investigating this correlation using optical tweezers with a healthy control group, a diabetic group, and a diabetic group with retinopathy. A dual optical tweezers set-up is utilised to stretch the cells and calculate the extent of their deformability. The deformability of red blood cells from the diabetic groups is found to be significantly lower than that of the healthy control group. Finally fluctuation theorems are considered: the asymmetry of the distributions of probabilities of observing forward and backward trajectories of micro-particles, and how this changes with the duration of the trajectories. Theoretical calculations are presented to find the fluctuation theorems for two methods of performing work on two hydrodynamically coupled particles. Simulations and trial experimental studies are performed to attempt to verify these calculations

sFlt-1 and NTproBNP independently predict mortality in a cohort of heart failure patients.

Objective: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a circulating receptor for VEGF-A. Recent reports of elevated plasma levels of sFlt-1 in coronary heart disease and heart failure (HF) motivated our study aimed at investigating the utility of sFlt-1 as a prognostic biomarker in heart failure patients. Methods: ELISA assays for sFlt-1 and NTproBNP were performed in n=858 patients from a prospective multicentre, observational study (the PEOPLE study) of outcome among patients after appropriate treatment for an episode of acute decompensated HF in New Zealand. Plasma was sampled at a baseline visit and stored at -80°C. Statistical tests were adjusted for patient age at baseline visit, skewed data were log-adjusted and the endpoint for clinical outcome analysis was all-cause death. Patients were followed for a median of 3.63 (range 0.74-5.50) years. Results: Mean baseline plasma sFlt-1 was 125 +/- 2.01 pg/ml. sFlt-1 was higher in patients with HF with reduced ejection fraction (HFrEF) (130 +/- 2.62 pg/ml, n=553) compared to those with HF with preserved EF (HFpEF) (117 +/-3.59 pg/ml, n=305; p=0.005). sFlt-1 correlated with heart rate (r=0.148, p<0.001), systolic blood pressure (r=-0.139, p<0.001) and LVEF (r=-0.088, p=0.019). A Cox proportional hazards model showed sFlt-1 was a predictor of all-cause death (HR=6.30, p<0.001) in the PEOPLE cohort independent of age, NTproBNP, ischaemic aetiology, and NYHA class (n=842, 274 deaths), established predictors of mortality in the PEOPLE cohort. Conclusion: sFlt-1 levels at baseline should be investigated further as a predictor of death; complementary to established prognostic biomarkers in heart failure

A Candidate Sub-Parsec Supermassive Binary Black Hole System

We identify SDSS J153636.22+044127.0, a QSO discovered in the Sloan Digital Sky Survey, as a promising candidate for a binary black hole system. This QSO has two broad-line emission systems separated by 3500 km/sec. The redder system at z=0.3889 also has a typical set of narrow forbidden lines. The bluer system (z=0.3727) shows only broad Balmer lines and UV Fe II emission, making it highly unusual in its lack of narrow lines. A third system, which includes only unresolved absorption lines, is seen at a redshift, z=0.3878, intermediate between the two emission-line systems. While the observational signatures of binary nuclear black holes remain unclear, J1536+0441 is unique among all QSOs known in having two broad-line regions, indicative of two separate black holes presently accreting gas. The interpretation of this as a bound binary system of two black holes having masses of 10^8.9 and 10^7.3 solar masses, yields a separation of ~ 0.1 parsec and an orbital period of ~100 years. The separation implies that the two black holes are orbiting within a single narrow-line region, consistent with the characteristics of the spectrum. This object was identified as an extreme outlier of a Karhunen-Loeve Transform of 17,500 z < 0.7 QSO spectra from the SDSS. The probability of the spectrum resulting from a chance superposition of two QSOs with similar redshifts is estimated at 2X10^-7, leading to the expectation of 0.003 such objects in the sample studied; however, even in this case, the spectrum of the lower redshift QSO remains highly unusual.Comment: 8 pages, 2 figures, Nature in pres

Are bed bug infestations on the increase within Greater London

The objective of the study was to determine whether the number of properties infested with bed bugs in Greater London is increasing. Data sets for seven Boroughs within Greater London containing the number of telephone calls received by pest control teams from members of the public seeking treatment for bed bug and other major domestic pest infestations (cockroaches, fleas, mice, rats and Pharaoh’s ants), from January 2000 to June 2006, were analysed. The absolute increase of calls concerning bed bugs increased from 2000-2006 by an average of 28.5 (95%CI: 6.9-50.3) per annum and the proportion of calls concerning bed bugs, as opposed to other major domestic pests, increased by an average of 24.7% (95%CI: 17.2-32.7) p.a. Calls followed up during July across each of the seven boroughs confirmed bed bug infestations. Twenty two adult specimens were collected and identified as the common bed bug, Cimex lectularius. Monthly data obtained from six Boroughs identified the greatest number of bed bug calls in late summer (August and September) and cyclic peaks with periods of 12, 6 and 2 months were also identified. In conclusion, the number of calls concerning bed bugs increased in Greater London from 2000-2006. This reflects a trend found in other major national and international developed cities. Contributing factors are likely to be passive dispersal, due to a growth in international travel and second-hand furniture sales, lack of awareness of bed bug infestations, due to the crevice-dwelling behaviour of bed bugs, and ineffective control, due to bed bug resistance to insecticides and a move from broad-spectrum insecticides. Within the UK, there is a need for additional monitoring and a code of practice for the control of public health pests including bed bugs

A microscopic Kapitza pendulum

Pyotr Kapitza studied in 1951 the unusual equilibrium features of a rigid pendulum when its point of suspension is under a high-frequency vertical vibration. A sufficiently fast vibration makes the top position stable, putting the pendulum in an inverted orientation that seemingly defies gravity. Kapitza’s analytical method, based on an asymptotic separation of fast and slow variables yielding a renormalized potential, has found application in many diverse areas. Here we study Kapitza’s pendulum going beyond its typical idealizations, by explicitly considering its finite stiffness and the dissipative interaction with the surrounding medium, and using similar theoretical methods as Kapitza. The pendulum is realized at the micrometre scale using a colloidal particle suspended in water and trapped by optical tweezers. Though the strong dissipation present at this scale prevents the inverted pendulum regime, new ones appear in which the equilibrium positions are displaced to the side, and with transitions between them determined either by the driving frequency or the friction coefficient. These new regimes could be exploited in applications aimed at particle separation at small scales

Stretching red blood cells with optical tweezers

In this work we report on experiments to measure the deformability of red blood cells (RBCs) when subject to stretching with optical tweezers. Individual red blood cells are trapped directly in a dual optical tweezers, and subject to a stretching protocol that is the same for all cells under test. Differences in the resulting extension are therefore indicative of differences in cell deformability. The targets for investigation are RBCs taken from patients with type 2 diabetes mellitus (T2DM) who exhibit diabetic retinopathy (DR), and from patients with birdshot chorioretinopathy (BCR). We find a statistically significant change in deformability for RBCs from DR patients compared to a control group, but no significant change for BCR patients. These results offer support to the importance of the role of RBC biomechanical properties in the progress of these conditions

Dust-free quasars in the early Universe

The most distant quasars known, at redshifts z=6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands. This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z=6 quasar was shown not to have any detectable emission from hot dust, but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z=6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z=6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.Comment: To be published in Nature on the 18 March 2010

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region

Cosmic Hydrogen Was Significantly Neutral a Billion Years After the Big Bang

The ionization fraction of cosmic hydrogen, left over from the big bang, provides crucial fossil evidence for when the first stars and quasar black holes formed in the infant universe. Spectra of the two most distant quasars known show nearly complete absorption of photons with wavelengths shorter than the Ly-alpha transition of neutral hydrogen, indicating that hydrogen in the intergalactic medium (IGM) had not been completely ionized at a redshift z~6.3, about a billion years after the big bang. Here we show that the radii of influence of ionizing radiation from these quasars imply that the surrounding IGM had a neutral hydrogen fraction of tens of percent prior to the quasar activity, much higher than previous lower limits of ~0.1%. When combined with the recent inference of a large cumulative optical depth to electron scattering after cosmological recombination from the WMAP data, our result suggests the existence of a second peak in the mean ionization history, potentially due to an early formation episode of the first stars.Comment: 14 Pages, 2 Figures. Accepted for publication in Nature. Press embargo until publishe

Molecular Gas in the Host Galaxy of a Quasar at Redshift z=6.42

Observations of the molecular gas phase in quasar host galaxies provide fundamental constraints on galaxy evolution at the highest redshifts. Molecular gas is the material out of which stars form; it can be traced by spectral line emission of carbon--monoxide (CO). To date, CO emission has been detected in more than a dozen quasar host galaxies with redshifts (z) larger 2, the record holder being at z=4.69. At these distances the CO lines are shifted to longer wavelengths, enabling their observation with sensitive radio and millimetre interferometers. Here we present the discovery of CO emission toward the quasar SDSS J114816.64+525150.3 (hereafter J1148+5251) at a redshift of z=6.42, when the universe was only 1/16 of its present age. This is the first detection of molecular gas at the end of cosmic reionization. The presence of large amounts of molecular gas (M(H_2)=2.2e10 M_sun) in an object at this time demonstrates that heavy element enriched molecular gas can be generated rapidly in the earliest galaxies.Comment: 12 pages, 2 figures. To appear in Nature, July, 200