Sensing and Actuation from Biology to Electronics

We introduce an in vitro diagnostic magnetic biosensing platform for immunoassay and nucleic acid detection. The platform has key characteristics for a point-of-use (POU) diagnostic: portability, low-power consumption, low cost, and multiplexing capability. As a demonstration of capabilities, we use this platform for the room temperature, amplification-free detection of a 31 bp DNA oligomer and interferon-gamma (a protein relevant for tuberculosis diagnosis). Reliable assay measurements down to 100 pM for the DNA and 1 pM for the protein are demonstrated. We introduce a novel "magnetic freezing" technique for baseline measurement elimination and to enable spatial multiplexing. We have created a general protocol for adapting integrated circuit (IC) sensors to any of hundreds of commercially available immunoassay kits and custom designed DNA sequences.

We also introduce a method for immunotherapy treatment of malignant gliomas. We utilize leukocytes internalized with immunostimulatory nanoparticle-oligonucleotide conjugates to localize and retain immune cells near the tumor site. As a proof-of-principle, we develop a novel cell imaging and incubation chamber for in vitro magnetic motility experiments. We use the apparatus to demonstrate the controlled movement of magnetically loaded THP-1 leukocytes.

Finally, we introduce an IC transmitter and power ampli er (PA) that utilizes electronic digital infrastructure, sensors, and actuators to self-heal and adapt to process, dynamic, and environmental variation. Traditional IC design has achieved incredible degrees of reliability by ensuring that billions of transistors on a single IC die are all simultaneously functional. Reliability becomes increasingly difficult as the size of a transistor shrinks. Self-healing can mitigate these variations.

Biology of the amphipod Gammarus pulex L. in water-bodies of the Leningrad district, and its piscicultural importance [Translation from: Trudy Vsesoyuznogo Gidrobiologicheskogo Obshchestva 7 99-122, 1956]

Observations and laboratory experiments are summarised that examine the widely discussed issue of what Gammarus pulex feeds on. On the basis of the observations of the authors and data from the literature it can be noted that G. pulex belongs to the omnivorous organisms, but, depending on the conditions of subsistence, in its rations either plant or animal food can predominate.

A study of the reproductive biology of dace in the middle Ob [introduction , summary and table captions only] [Translation from: Trudy tomsk. gos. Univ. 125, pp.77-91]

The Siberian Dace (Leuciscus leuciscus baicalensis (Dyb)is an important trade fish in Siberian waters. In the Ob basin more than 30,000 centners are produced annually. Catches of dace fluctuate significantly both between different rivers and between years in the Tomsk region. Defining the stocks of dace in the waters of the Tomsk region and explaining the fluctuations over time seems to be a very important and relevant question for the workers of the fishing industry. An answer, however, requires an accurate knowledge of the biology of dace; its reproductive, feeding and migration habits and the conditions of wintering etc. In the following we examine one of the above questions i.e. the biology of the reproduction of dace. The study was carried out in the Middle Ob in May 1951. This tranlations provides the introduction, summary and table captions only of the original article.

Changes in feeding biology of Nile tilapia, Oreochromis niloticus (L.), after invasion of water hyacinth, Eichhornia crassipes (Mart.) Solms, in Lake Victoria, Kenya

Oreochrimis niloticus (L.) was introduced to Lake victoria in the 1950s. It remained relatively uncommon in catches until 1965, when the numbers began to increase dramatically. It is now the third most important commercial fish species after the Nile perch, Lates niloticus (L.) and Rastrineobola argentea (Pellegrin). Oreochromis niloticus is considered a herbivore, feeding mostly on algae and plant material. The diet now appears to be more diversified , with insects, fish, algae and plant materials all being important food items. Fish smaller than 5 cm TL have a diverse diet but there is a decline in the importance of zooplankton, the preferred food item of small fish, as fish get larger. The shift in diet could be due to changes which have occurred in the lake. Water hyacinth, Eichhornia crassipes (Mart.) Solms, which harbours numerous insects in its root balls, now has extensively coverage over the lake. The native fish species which preyed on these insects (e.g. haplochromines) have largely been eliminated and O. niloticus could be filling niches previously occupied by these cichlids and non cichlid fishes. The change in diet could also be related to food availability and abundance where the fish is feeding on the most readily available food items.

Reproductive biology of Rastrineobola argentea (Pellegrin) in the northern waters of Lake Victoria

Size at first maturity, breeding periods and condition factor were determined for the small pelagic cyprinid Rastrineobola argentea (Pellegrin) in the Jinja waters of Lake Victoria in 1996-1997. Females showed a reduced size at maturity compared to ten years earlier when exploitation of the species was minimal. The males, however, have changed little. Although the species breeds throughout the year, two breeding peaks were observed during the drier months of August and December-January. Minimal breeding was observed in the rainy months of April-May and October-November. Fish from the open water station at Bugaia showed a higher proportion of breeding individuals than those from inshore areas. The mean monthly condition factor of fish from Napoleon Gulf confirmed breeding peaks obtained from examination of gonad development.

Reproductive biology of Oreochromis niloticus (L.) in the Nyanza Gulf of Lake Victoria

The reproduction of Nile tilapia, Oreochromis niloticus (L.), in the Nyanza Gulf of Lake Victoria was studied from June 1998 to May 1999. Length at maturity ranged from 28-30 cm TL for females and from 32-34 cm TL for males. Males were more abundant in all length classes longer than 36 cm TL. Relative condition factor was above unity, except in August, October and May for males, and October for females. Gonadosomatic index (GSI) was low during the post spawning period (July to October) and high during the protracted breeding period (December-June).

Computational microscopy: turning megapixels into gigapixels

The layout of a typical optical microscope has remained effectively unchanged over the past century. Besides the widespread adoption of digital focal plane arrays, relatively few innovations have helped improve standard imaging with bright-field microscopes. This thesis presents a new microscope imaging method, termed Fourier ptychography, which uses an LED to provide variable sample illumination and post-processing algorithms to recover useful sample information. Examples include increasing the resolution of megapixel-scale images to one gigapixel, measuring quantitative phase, achieving oil-immersion quality resolution without an immersion medium, and recovering complex three dimensional sample structure.

Aspects of the biology of coarse fish in the Dorset Stour

Some of the results from an investigation of five species of coarse fish, in the Stour River, carried out from 1968-1978 are presented in this article. The species involved were: Rutilus rutilis, Leuciscus leuciscus, L. cephalus, Esox lucius and Perca fluviatilis : which are of particular interest to anglers. Although these species show some similarities, as in the shape of the annual and seasonal growth curves, in most other respects each species occupies a distinct niche in the ecosystem and has a life-history strategy peculiar to itself. In this study only 5 species were investigated. When all the species present are considered the relationships or diversities suggested here will therefore be made far more complex.

A novel three-dimensional imaging array recording and computational method by means of coded cameras reconstruction

In this paper, we propose a novel three-dimensional imaging method by which the object is captured by a coded cameras array (CCA) and computationally reconstructed as a series of longitudinal layered surface images of the object. The distribution of cameras in array, named code pattern, is crucial for reconstructed images fidelity when the correlation decoding is used. We use DIRECT global optimization algorithm to design the code patterns that possess proper imaging property. We have conducted primary experiments to verify and test the performance of the proposed method with a simple discontinuous object and a small-scale CCA including nine cameras. After certain procedures such as capturing, photograph integrating, computational reconstructing and filtering, etc., we obtain reconstructed longitudinal layered surface images of the object with higher signal-to-noise ratio. The results of experiments show that the proposed method is feasible. It is a promising method to be used in fields such as remote sensing, machine vision, etc. (c) 2006 Elsevier GmbH. All rights reserved.

Towards in situ Single Cell Systems Biology

Systems-level studies of biological systems rely on observations taken at a resolution lower than the essential unit of biology, the cell. Recent technical advances in DNA sequencing have enabled measurements of the transcriptomes in single cells excised from their environment, but it remains a daunting technical problem to reconstruct in situ gene expression patterns from sequencing data. In this thesis I develop methods for the routine, quantitative in situ measurement of gene expression using fluorescence microscopy.

The number of molecular species that can be measured simultaneously by fluorescence microscopy is limited by the pallet of spectrally distinct fluorophores. Thus, fluorescence microscopy is traditionally limited to the simultaneous measurement of only five labeled biomolecules at a time. The two methods described in this thesis, super-resolution barcoding and temporal barcoding, represent strategies for overcoming this limitation to monitor expression of many genes in a single cell. Super-resolution barcoding employs optical super-resolution microscopy (SRM) and combinatorial labeling via-smFISH (single molecule fluorescence in situ hybridization) to uniquely label individual mRNA species with distinct barcodes resolvable at nanometer resolution. This method dramatically increases the optical space in a cell, allowing a large numbers of barcodes to be visualized simultaneously. As a proof of principle this technology was used to study the S. cerevisiae calcium stress response. The second method, sequential barcoding, reads out a temporal barcode through multiple rounds of oligonucleotide hybridization to the same mRNA. The multiplexing capacity of sequential barcoding increases exponentially with the number of rounds of hybridization, allowing over a hundred genes to be profiled in only a few rounds of hybridization.

The utility of sequential barcoding was further demonstrated by adapting this method to study gene expression in mammalian tissues. Mammalian tissues suffer both from a large amount of auto-fluorescence and light scattering, making detection of smFISH probes on mRNA difficult. An amplified single molecule detection technology, smHCR (single molecule hairpin chain reaction), was developed to allow for the quantification of mRNA in tissue. This technology is demonstrated in combination with light sheet microscopy and background reducing tissue clearing technology, enabling whole-organ sequential barcoding to monitor in situ gene expression directly in intact mammalian tissue.

The methods presented in this thesis, specifically sequential barcoding and smHCR, enable multiplexed transcriptional observations in any tissue of interest. These technologies will serve as a general platform for future transcriptomic studies of complex tissues.

Computational Microscopy: Breaking the Limit of Conventional Optics

Computational imaging is flourishing thanks to the recent advancement in array photodetectors and image processing algorithms. This thesis presents Fourier ptychography, which is a computational imaging technique implemented in microscopy to break the limit of conventional optics. With the implementation of Fourier ptychography, the resolution of the imaging system can surpass the diffraction limit of the objective lens's numerical aperture; the quantitative phase information of a sample can be reconstructed from intensity-only measurements; and the aberration of a microscope system can be characterized and computationally corrected. This computational microscopy technique enhances the performance of conventional optical systems and expands the scope of their applications.

The impact of molecular biology on assessment of water quality: advantages and limitations of current techniques

The advent of molecular biology has had a dramatic impact on all aspects of biology, not least applied microbial ecology. Microbiological testing of water has traditionally depended largely on culture techniques. Growing understanding that only a small proportion of microbial species are culturable, and that many microorganisms may attain a viable but non-culturable state, has promoted the development of novel approaches to monitoring pathogens in the environment. This has been paralleled by an increased awareness of the surprising genetic diversity of natural microbial populations. By targeting gene sequences that are specific for particular microorganisms, for example genes that encode diagnostic enzymes, or species-specific domains of conserved genes such as 16S ribosomal RNA coding sequences (rrn genes), the problems of culture can be avoided. Technical developments, notably in the area of in vitro amplification of DNA using the polymerase chain reaction (PCR), now permit routine detection and identification of specific microorganisms, even when present in very low numbers. Although the techniques of molecular biology have provided some very powerful tools for environmental microbiology, it should not be forgotten that these have their own drawbacks and biases in sampling. For example, molecular techniques are dependent on efficient lysis and recovery of nucleic acids from both vegetative forms and spores of microbial species that may differ radically when growing in the laboratory compared with the natural environment. Furthermore, PCR amplification can introduce its own bias depending on the nature of the oligonucleotide primers utilised. However, despite these potential caveats, it seems likely that a molecular biological approach, particularly with its potential for automation, will provide the mainstay of diagnostic technology for the foreseeable future.

Freshwater biology and water supply in Britain

This paper is designed to give a general account of freshwater biology as it bears on waterworks practice. Most water that is used for consumption will commonly go through a storage reservoir. Here special reference is given to the biological relations in standing waters, the biological control of water supplies, methods of plankton estimation, the biology of slow sand filtration and the use of algicides.