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Biomedical subjects

M P MacDonald

Publications and source records attributed to M P MacDonald.

6 recordsLinked to original sources

Microfluidic sorting in an optical lattice.

The response of a microscopic dielectric object to an applied light field can profoundly affect its kinetic motion. A classic example of this is an optical trap, which can hold a particle in a tightly focused light beam. Optical fields can also be used to arrange, guide or deflect particles in appropriate light-field geometries. Here we demonstrate an optical sorter for microscopic particles that exploits the interaction of particles-biological or otherwise-with an extended, interlinked, dynamically reconfigurable, three-dimensional optical lattice. The strength of this interaction with the lattice sites depends on the optical polarizability of the particles, giving tunable selection criteria. We demonstrate both sorting by size (of protein microcapsule drug delivery agents) and sorting by refractive index (of other colloidal particle streams). The sorting efficiency of this method approaches 100%, with values of 96% or more observed even for concentrated solutions with throughputs exceeding those reported for fluorescence-activated cell sorting. This powerful, non-invasive technique is suited to sorting and fractionation within integrated ('lab-on-a-chip') microfluidic systems, and can be applied in colloidal, molecular and biological research.

Capsules↗

Creation and manipulation of three-dimensional optically trapped structures.

An interferometric pattern between two annular laser beams is used to construct three-dimensional (3D) trapped structures within an optical tweezers setup. In addition to being fully translatable in three dimensions, the trapped structure can be rotated controllably and continuously by introducing a frequency difference between the two laser beams. These interference patterns could play an important role in the creation of extended 3D crystalline structures.

Journal Article↗

Controlled rotation of optically trapped microscopic particles.

We demonstrate controlled rotation of optically trapped objects in a spiral interference pattern. This pattern is generated by interfering an annular shaped laser beam with a reference beam. Objects are trapped in the spiral arms of the pattern. Changing the optical path length causes this pattern, and thus the trapped objects, to rotate. Structures of silica microspheres, microscopic glass rods, and chromosomes are set into rotation at rates in excess of 5 hertz. This technique does not depend on intrinsic properties of the trapped particle and thus offers important applications in optical and biological micromachines.

Animals↗

Age-related changes in sucrase and lactase activity in the small intestine of 3- and 10-week-old obese mice (C57BL/6Jobob).

The relationship between obesity and the digestion of carbohydrates is poorly understood. Data in humans have provided conflicting results. Studies using the obese mouse (C57BL/6Jobob) suggest that obesity is associated with increased activity of intestinal alpha-disaccharidases. To evaluate the developmental pattern of these enzyme activities in obesity, we determined the activity of sucrase and lactase in the small intestine of genetically obese mice (C57BL/6Jobob) and lean littermates at 3 and 10 weeks of age. Sucrase and lactase activities were measured on intestinal homogenates from segments of the small intestine in mice maintained on standard laboratory diets during the postweaning period. Results were expressed as specific activity and total activity per intestinal segment. Obese mice did not differ from lean littermates in body weight at 3 weeks of age, but exhibited increased protein content in the proximal small intestine. Sucrase specific activity was significantly higher in the obese mice at 3 weeks of age in all intestinal segments. Sucrase total activity showed a similar pattern. At 10 weeks of age, body weights of obese mice were substantially greater than the lean littermates. Sucrase specific and total activities were also greater in the obese mice at 10 weeks of age. Lactase specific activity, however, was similar in both obese and lean mice at both ages studied. Lactase total activity was greater in the obese mice, consistent with their greater intestinal mass. These observations demonstrate that changes in the intestinal sucrase activity of the obese mouse precede the development of excessive body weight.

Age Factors↗

Effect of a high-dextrose diet on sucrase and lactase activity in jejunum of obese mice (C57BL/6J obob).

The activities of intestinal disaccharidases are known to be responsive to changes in the dietary intake of carbohydrates in the adult rat. Little is known, however, regarding the activities of these enzymes in obese subjects and how they are affected by differing carbohydrate intakes. To evaluate the effect of carbohydrate intake on the activity of intestinal disaccharidases in obesity, we used the genetically obese mouse C57BL/6J obob as an experimental model. Representing an example of early-onset obesity and mature-onset diabetes, this animal is characteristically hyperinsulinemic and hyperglycemic. Groups of obese mice and lean littermates were fed for 7 weeks equal amounts of either high-dextrose or low-dextrose isoenergetic diets. Sucrase, maltase, and lactase activities were measured on intestinal homogenates from the proximal and middle portions of the jejunoileum (upper and lower jejunum). Results were expressed as activity per tissue protein as well as total activity. Obese mice were found to have consistently greater total activity of both sucrase and maltase than their lean littermates, mostly as a result of increased intestinal size. Total lactase activity, however, was similar in the upper jejunum in both obese and lean mice, largely related to a decreased specific activity in obese mice. All mice fed the high-dextrose diet had significantly increased total activity of all disaccharidases studied when compared to the low-dextrose-fed animals, except for the lactase activity in the lower jejunum, where no differences were found in either group. Increases in activity related to high carbohydrate intake were a result of increases in specific activity.

Animals↗

Cell cytometry with a light touch: sorting microscopic matter with an optical lattice.

Lab-on-a-chip design is a key technology for increasing both the reliability and the functionality of many different preparation and diagnostic techniques in biomedicine. The drive towards ever more integrated lab-on-a-chip designs requires increasingly complex microfluidic systems. In order to build these systems, non-invasive actuators such as pumps, filters and mixers are required. We have demonstrated microfluidic sorting based on a 3D interference pattern, formed from multiple coherent laser beams, which has the potential to fulfil all the above criteria. By interfering five laser beams from a fibre laser at 1070 nm, we have formed a 3D optical lattice. When particles flow through the optical lattice their trajectories depend upon the force exerted on the particle by the optical lattice, in combination with the drag force exerted by the fluid flow. Hence, with the strength of a particle's interaction with the lattice determining the total force exerted upon it, its trajectory is determined by its physical properties. These properties include refractive index, size and shape, giving a range of criteria with which to sort an analyte. We have shown separation at 45 degrees of polymer from silica microspheres (by refractive index), the separation of protein microcapsules and the sorting of erythrocytes from lymphocytes. The interference pattern can be tailored to the particles and if a blockage occurs, the laser can simply be switched off, unlike solid-state micro-sorters, so that no jamming occurs. Efficiencies in excess of 95% have been achieved.

Animals↗