Daniel A. Bartholomeusz

Personal sensors for the diagnosis and management of metabolic disorders

Luminescence-based analysis that facilitates the measurement of multiple metabolites from small sample volumes for use in point-of-care or in-home environments. Part of our interest in this project is in patient empowerment-getting patients to assume responsibility and control of their own diseases. Our goal is a Chem-Chip system that is analogous to the present generation of glucose dipsticks and glucometers in terms of ease of use, quality of data, and low cost. If the potential of the Chem-Chip is realized, practically all relevant disease markers over a wide range of molecular weights and concentrations could be quantitatively and specifically measured for disease diagnosis and management.

Multi-analyte bioluminescence-based disposable ChemChips for home-based application: Update

Bio- and chemi-luminescent based biochemical sensors are being developed in a multi-well single use format for multi-analyte applications employing a single step, disposable, easy to use and interpret ChemChip. We briefly review and summarize earlier and ongoing work. We also argue for far more, rather than less or limited, chemical data in all areas, and particularly in education, health, and medicine.

Optical enhanced luminescent measurements and sequential reagent mixing on a centrifugal microfluidic device for multi-analyte point-of-care applications

A centrifugal-based microfluidic device1 was built with lyophilized bioluminescent reagents for measuring multiple metabolites from a sample of less than 15 μL. Microfluidic channels, reaction wells, and valves were cut in adhesive vinyl film using a knife plotter with features down to 30 μm and transferred to metalized polycarbonate compact disks (CDs). The fabrication method was simple enough to test over 100 prototypes within a few months. It also allowed enzymes to be packaged in microchannels without exposure to heat or chemicals. The valves were rendered hydrophobic using liquid phase deposition. Microchannels were patterned using soft lithography to make them hydrophilic. Reagents and calibration standards were deposited and lyophilized in different wells before being covered with another adhesive film. Sample delivery was controlled by a modified CD ROM. The CD was capable of distributing 200 nL sample aliquots to 36 channels, each with a different set of reagents that mixed with the sample before initiating the luminescent reactions. Reflection of light from the metalized layer and lens configuration allowed for 20% of the available light to be collected from each channel. ATP was detected down to 0.1 μM. Creatinine, glucose, and galactose were also measured in micro and milliMolar ranges. Other optical-based analytical assays can easily be incorporated into the device design. The minimal sample size needed and expandability of the device make it easier to simultaneously measure a variety of clinically relevant analytes in point-of-care settings.

Bioluminescent based chemchip for point-of-care diagnostics

The design and progress of a MEMS prototype biochip device, which uses bioluminescence as a means for detecting a potential of 10-100 total analytes from biofluid samples, is discussed. Light enhancement was explored by coating etched square chambers with chromium and silver. Light enhancement was also investigated by observing the transmittance of light along micro channels molded in PDMS. Bioluminescent light generated from a 1-mM ATP with firefly luciferase/luciferin solution was placed inside the channels and chambers and the light output was observed through a close up lens by a CCD. Light enhancement effectiveness was determined from the CCD count increase per nL of sample volume for the cross sectional viewing areas of the channels or chambers. Uncoated silicon, chromium coated and silver coated square chambers enhanced light output about 1-4 CCD counts/nL, 3-13 CCD counts/nL, and 300 to 1,300 CCD counts/nL respectively. Uncoated PDMS channels enhance light by about 79-101 CCD counts/nL.