Harvey W. Ko

An automated, handheld biosensor for aflatoxin

A new immunoaffinity fluorometric biosensor has been developed for detecting and quantifying aflatoxins, a family of potent fungi-produced carcinogens that are commonly found in a variety of agriculture products. They have also been cited as a biological agent under weapons development. The handheld, self-contained biosensor is fully automatic, highly sensitive, quick, quantitative, and requires no special storage. Approximately 100 measurements can be made before refurbishment is required, and concentrations from 0.1 parts per billion (ppb) to 50 ppb can be determined in <2 min with a 1 ml sample volume. The device operates on the principles of immunoaffinity for specificity and fluorescence for a quantitative assay. The analytic procedure is flexible so that other chemical and biological analytes could be detected with minor modifications to the current device. Advances in electro-optical components, electronics, and miniaturized fluidics were combined to produce this reliable, small, and versatile instrument.

A noninvasive electromagnetic conductivity sensor for biomedical applications

The authors present the theory and practice of using a simple coil sensor operated at high frequency (1-10 MHz) to measure changes in conductivity in a biological sample. Explicit results are obtained for symmetric configurations that are useful for calibrating the device and making order-of-magnitude estimates of the results of applying the technique to humans to monitor the onset and progress of brain edema. A simple model suggests that the technique may be able to successfully measure the onset of some medical complications using the technology described.<<ETX>>

In vivo measurement of tumor conductiveness with the magnetic bioimpedance method

A noninvasive electromagnetic method has been developed that can effectively measure the in-vivo conductivity difference between rat tumor lines having a low and high metastatic potential. These tumor lines are used in the study of human prostate tumor.

Radar coverage predictions through time- and range-dependent refractive atmospheres with planetary boundary layer and electromagnetic parabolic equation models

The enhancement of the capability of electromagnetic parabolic equation (EMPE) and other propagation codes by using predictions from an atmospheric forecast model to provide refractivity data for range-dependent and time-varying situations is demonstrated. Starting from measured temperature and humidity data at one location and time, the JHU/APL planetary boundary layer model is used to obtained predictions for a 24-h forecast period. Predicted fields of temperature, humidity, and refractivity after 12 and 24 h are compared with measured data to verify the forecast, and vertical profiles of refractivity for each hour are provided, along with appropriate radar parameters, as input to EMPE. The EMPE calculations of expected radiation patterns as functions of height and range at selected times demonstrate the effects of hourly changes in the structure of the lower atmosphere on radar propagation. The radar propagation calculations have been repeated using the IREPS code to illustrate the similarities and differences between the two models when applied to this somewhat idealized, horizontally homogeneous situation.<<ETX>>

Bioimpedance: Novel Use of a Minimally Invasive Technique for Cancer Localization in the Intact Prostate

BACKGROUND. Prostate cancer is presently diagnosed by transrectal ultrasound (TRUS)guided sextant needle biopsy. While echo texture of the tissue can prompt localization of tumor, it is presently imprecise. From 50‐75% of men biopsied, based on an abnormal digital rectal examination (DRE) or elevated prostate-specific antigen (PSA) level, have negative biopsy results. Improvements in tumor localization during TRUS-guided prostate biopsy are greatly needed. Bioimpedance is an electrical property of biologic tissue. Electric current is limited in living tissue by highly insulating cell membranes; however, different tissue architecture such as cancer may impede current differently and allow detection of differences between normal and abnormal or malignant prostate tissue. Our goal was to assess the utility of bioimpedance measurements in differentiating tumor from normal prostatic tissue in an ex vivo model. METHODS. Bioimpedance was measured in six ex vivo prostates, which were removed for clinically localized prostate cancer. Two bioimpedance needles, 1 mm apart, were inserted 3 mm into the posterior surface of the prostate an average of 16 times per gland. Frequencies ranging from 100 kHz‐4 MHz were used to obtain 594 bioimpedance measurements from the six glands. These measurements were then correlated with histology to determine the presence or absence of prostate cancer. RESULTS. Prostate cancer was found to have a higher impedance, of 932 ± 170 ohms, compared to areas of no cancer within the same prostate, 751 ± 151 ohms, P < 0.0001, at 2 MHz. This phenomenon was observed across all frequencies tested. CONCLUSIONS. This study demonstrates for the first time application of bioimpedance to distinguish areas of prostate cancer from areas of normal prostate. This technology may improve identification and localization of cancer within the prostate. Moreover, bioimpedance can potentially guide needle placement during prostate biopsy and thus improve sampling of tumors. Currently, our ex vivo model is limited by variables such as temperature and lack of blood flow. Further studies in an in vivo model will be needed to assess their effect. Prostate 39:213‐218, 1999.

Development of an automated handheld immunoaffinity fluorometric biosensor

A new immunoaffinity fluorometric biosensor has been developed for detecting and quantifying aflatoxins, a family of potent fungi-produced carcinogens that are commonly found in a variety of agriculture products. They have also been cited as a biological agent under weapons development. The handheld, self-contained biosensor is fully automatic, highly sensitive, quick, quantitative, and requires no special storage. Concentration from 0.1 parts per billion to 50 ppb can be determined in less than 2 minutes with a 1 ml sample volume. Higher concentrations can be determined by simply reducing the sample volume. The device operates on the principles of immunoaffinity for specificity and fluorescence for a quantitative assay. The analytic procedure is flexible so that other chemical and biological analytes could be detected with minor modifications to the current device.

Electromagnetic holographic imaging of bioimpedance

The electromagnetic bioimpedance method has successfully measured the very subtle conductivity changes associated with brain edema and prostate tumor. This method provides noninvasive measurements using non-ionizing magnetic fields applied with a small coil that avoids the use of contact electrodes. This paper introduces results from combining a holographic signal processing algorithm and a low power coil system that helps provide the 3D image of impedance contrast that should make the noninvasive electromagnetic bioimpedance method useful in health care.

In-vivo measurement of brain edema with the magnetic bio-impedance method

A noninvasive electromagnetic method has been examined that can effectively measure the rapid onset of vasogenic brain edema. Electrical conductivity of normal and edematous brain tissue obtained by this method at frequencies between 1 and 10 MHz is consistent with values obtained with invasive conductivity probes.

Tiny-TOF Mass Spectrometer for Biodetection

The mass spectrometer has long been known as the most powerful analytical tool in the laboratory for analysis of a broad spectrum of chemical and biological materials. The applicability of mass spectrometers to field detection problems has been quite limited given the large size, heavy weight, and prohibitive power requirements of the instrumentation. However, this situation is rapidly changing, as the need for field-portable detection systems becomes more critical. This paper reports on an effort to bring small, yet powerful, time-of-flight (TOF) mass spectrometer technology to bear on the chemical and biological detection problem. In order to achieve this goal, not only must small instrumentation be developed and fielded, but validated mass spectral signatures for all of the agents of interest must also be obtained. We will describe the development of a miniaturized time-of-flight mass spectrometer (tinyTOF) for field portable biodetection. Topics to be covered include: operating principles of the mass analyzer; miniaturization of the mass analyzer and other system components; mass spectral biosignatures; and the sample interface for airborne particulate samples.

Reply by the authors to the discussion by M. Zhdanov

The work described in our paper is an inverse source problem using a back propagation approach to reconstruct the field distribution below the surface based on surface field measurements. The algorithm we developed is consistent with quasi‐static diffusion field conditions and uses spatial transforms to reconstruct the below surface image. The result is an efficient method of identifying the location and orientation of underground objects within the near field of excitation coils on the surface.