Paramagnetic capture mode magnetophoretic microseparator for blood cells.

The paper presents the characterisation of a continuous paramagnetic capture (PMC) mode magnetophoretic microseparator for separating red and white blood cells from whole blood based on their native magnetic properties. The PMC microseparator separates the blood cells using a high-gradient magnetic separation method without the use of additives such as magnetic tagging. The microseparator is fabricated using microfabrication technology, enabling the integration of micro-scale magnetic flux concentrators in an aqueous micro-environment. Experimental results show that the PMC microseparator can continuously separate out 91.1% of red blood cells from whole blood within 5 min, using an external magnetic flux of 0.2 T from a permanent magnet. Monitoring of white blood cells dyed with a fluorescent probe shows that 87.7% of white blood cells are separated out by the 0.2 T external magnetic flux applied to the PMC microseparator.

High lane density slab-gel electrophoresis using micromachined instrumentation.

In this paper, micromachined pipette arrays (MPAs) and microcombs were studied as a means of enabling high lane density gel electrophoresis. The MPA provide a miniaturized format to interface sub-microliter volumes of samples between macroscale sample preparation formats and microscale biochemical analysis systems. The microcombs provide a means of creating sample loading wells in the gel material on the same center-to-center spacing as the MPAs. Together, the two micromachined instruments provide an alternative to current combs and pipetting technologies used for creating sample loading wells and sample delivery in gel electrophoresis systems. Using three designs for the microcomb-MPA pair, center-to-center spacings of 1.0 mm, 500 microm, and 250 microm are studied. The results demonstrate an approximate 10-fold increase in lane density and a 10-fold reduction in sample size from 5 microL to 500 pL. As a result, the number of theoretical plates has increased 2.5-fold, while system resolution has increased 1.5-fold over the conventional agarose gel systems. An examination of changes in resolution across the width of individual separation lanes in both systems revealed dependence in the case of the conventional gels and no dependence for the gels loaded with the micromachined instrumentation.

Geometric scaling effects in electrical field flow fractionation. 1. Theoretical analysis.

This work outlines the fundamental scaling laws associated with electrical field flow fractionation channels. Although general FFF theory indicates few advantages from miniaturization, EFFF theory indicates clear advantages to miniaturization of the EFFF channel. Retention, plate heights, resolution, equilibration times, and time constants are examined. The outlined theory predicts scaling advantages in each of these areas after miniaturization. Potential applications, such as the use of these systems for sample preparation in microscale total analysis systems, and improvements associated with these theoretical predictions are also discussed.

Micromachined pipette arrays.

In this paper, the design and characterization of batch fabricated metallic micromachined pipette arrays is described. The process used to fabricate the micromachined pipette arrays (MPA) includes p+ etch-stop membrane technology, anisotropic etching of silicon in potassium hydroxide, sacrificial thick photoresist micromolding technology, and electrodeposition. Arrays of one to ten pipettes have been fabricated using nickel as the structural material and palladium as the biocompatible coating of inside walls. The inner dimensions of the individual pipettes fabricated to date range from 30 microns to 1.5 mm in width, 0.5 mm to several cm in length, and 5-50 microns in thickness. The center-to-center spacing of these pipettes varies from 100 microns to several centimeters. The MPA have a number of advantages when compared to the current micropipette technology, including the ability to transfer precise volumes of samples in the submicroliter range; the ability to manipulate samples, reagents, or buffers in a highly-parallel fashion by operating hundreds of individual pipettes simultaneously; and the compatibility with the submilimeter center-to-center dimensions of the microscale biochemical analysis systems. The application of the MPA to high lane density slab gel electrophoresis is explored. Sample wells are formed in agarose gels by using micromachined combs (solid MPA) at center-to-center spacing ranging from 250 microns to 1.9 mm. The samples are loaded using the MPA. The results of the micro-gel separations compare favorably with the standard mini-gel separations and show a twofold increase in the number of theoretical plates as well as a sixfold increase in lane density.

Micromachined needle arrays for drug delivery or fluid extraction.

Micromachined needle arrays have been designed, fabricated, and characterized. The design includes arrays of 25 needles with fluid coupling channels and dual structural supports. Numerical modeling of fluid flow characteristics was performed, demonstrating that the needle coupling channels redistribute flow when the input or output ports are fully restricted. Micromachining technologies have been used to batch fabricate hollow metallic fluid coupled needle arrays. The significance of this work includes the development of the hollow metallic micromachined needle arrays for biomedical applications, as well as a discussion of structural, fluidic, and biological design considerations. The micromachined needle array has many advantages, including (a) reduced trauma at penetration site (small size), (b) greater freedom of patient movement (minimal penetration), (c) a practically pain-free drug delivery device (distribution of force), (d) precise control of penetration depth (needle extension length), and (e) they can be stacked and packaged into a 3-D device for fluid transfer.

A micromachined electrical field-flow fractionation (mu-EFFF) system.

In this work, micromachining technologies are employed to develop a miniaturized electrical field-flow fractionation (EFFF) separation system. EFFF systems are used to separate colloidal particles such as cells, liposomes, proteins, or other particulates, and to characterize emulsions and other mixtures according to particle charge density. Macromachining techniques have been used to develop existing EFFF technologies. At the present time, the limiting factor in the development of higher precision EFFF separation systems has been the manufacturing approach. In this paper, the theory behind the operation and resolution of a micron-sized EFFF (mu-EFFF) system is described and the advantages to be gained from application of micromachining technologies are given, thus motivating the need for further miniaturization. A completely fabricated mu-EFFF system is developed, separations are performed, and the mu-EFFF system is compared to the theoretically predicted results as well as the results from current macro EFFF systems.

Development and implementation of a quality assurance program for mammography.

As a pilot study for a national campaign to promote the use of screening mammography, the Virginia Division of the American Cancer Society conducted a breast cancer awareness project with mammography screening. An important part of the program was the development of a quality assurance program for mammography. Guidelines were established for equipment, image recorders, processing, dose, and patient positioning. A survey of information about the mammographic equipment was conducted, and the mammograms from each facility were reviewed. A total of 63 mammographic units in 56 facilities statewide were included in the month-long program during which approximately 9,000 women were screened.

Complications from intraperitoneal radioactive phosphorus in ovarian malignancies.

A retrospective study of the use of phosphorus-32 in the treatment of 73 cases of ovarian malignancy to evaluate the safety and morbidity is presented. The surgically confirmed major complication rate with P-32 alone was 4 of 54 cases (7.4%). The addition of external radiation raised the surgically confirmed complication rate to 4 of 19 cases (21%) and with the addition of those diagnosed and treated only medically the rate rose to 8 of 19 cases (42%). In Stage I cases, Grades 1 and 2, there was only 1 death in 26 patients (96%), whereas for Grade 3 tumors only 6 of 12 patients (50%) were living at the end of 2 years.

Cooperative approach to the treatment of cervical cancer.

This study covers 20 years' experience in the treatment of carcinoma of the cervix. Improved results and a decreased rate of major complications are seen as a result of a cooperative approach in treatment planning and careful dosimetry. Comparisons are made with large treatment centers as well as with national survival rates. Preliminary results with improved radiotherapeutic techniques continue to show improvement in survival rates.

Preoperative radiation therapy in the management of squamous cell carcinoma of the vulva: preliminary report.

Fourteen cases of squamous cell carcinoma of the vulva treated preoperatively by use of cobalt-60 irradiation directed to the vulva and inguinal areas are reviewed. Toral dose varied from 3,600 to 5,500 rads according to reaction and tolerance. No treatments had to be interrupted due to excessive radiation effects. Surgical procedures were performed six weeks after irradiation. Histologic investigation of the surgical specimen showed no sign of tumor in five cases, almost complete regression in three, and a substantial reduction of the lesion in the remainder of the cases. In situ lesions surrounding the invasive tumors were cleared in three cases. Lymph node involvement was found in only two patients, one of whom did not receive preoperative radiation to in inguinal areas. Only one local recurrence was encountered and this was in the abdominal skin outside of the irradiated area. The healing process does not seem to be impaired after radiation treatment in spite of the fact that in many patients a very extensive type of surgical procedure was carried out.