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Programmable Nano Bio Chips

by: Eva Thomas

We would not have advanced in medicine if it were not for the diagnosis of conditions such as diabetes, cancer and other diseases through technology. Biosensors are devices that provide information about analytes, the chemicals to be investigated within the human body. The information provided by the biosensors can be analyzed to give diagnoses. These biosensors act with the same processes as the senses of smell and taste in that receptors on the tongue and in the nasal cavity bind specifically to detect chemicals. In the field of bioengineering, there is a movement towards miniaturized design which is driven by the necessity to be more cost-effective through the mass production of disposable devices. Beyond lower cost and increased availability, nanoscale assay technology offers rapid analysis and less waste of sample volumes.

Jesse V. Jokerst and John T. McDevitt have teamed up to research the creation of nanoscale diagnostics. Jokerst recently obtained his doctorate degree in chemistry with McDevitt at the University of Texas – Austin before McDevitt moved to Rice University. They condensed an entire clinical laboratory into a chip to form a Programmable Nano-Bio-Chip (PNBC) or what they have dubbed the “Lab- On-A-Chip.”6, 2, 1 The goal of the McDevitt lab at Rice University is to optimize this device by making it more accessible and affordable and by discovering more applications of the biosensors. The advantages of programmability include its modularity (with interchangeable parts), flexibility and the ability to process and learn new biomarker signatures, which are indicators of various conditions. The nanochip achieves large effects overcoming noise within the body even at nanoscale particularly because of the parallelization of the assay.1

The device was first designed as an electronic “taste chip”, as it emulates taste buds in its recognition of various substrates.1 A set of design criteria was considered during the development of the nano biosensors. A low cost of diagnosis would make the process more accessible. The employment of the device should be simple and easy to use. The device should be as small as possible to decrease invasiveness. The ability to test for multiple analytes would make the device more flexible and efficient. A quick reaction with a short turn around time would allow for a quicker response from the device.2 The device is intended to be $1 per test with a one-time use, disposable labcard. However, as the field of nanotechnology is still growing, there are difficulties in reaching these goals. The PNBCs are entirely self contained which make it different from other nanosensors which require laboratory support in clinics. Bioreactions occur and are subsequently measured on the chip.2 Agarose beads, acting as spongy capture agents, are conditioned, perhaps with antibodies, to be sensitive to the desired analytes.5 The 3D nature of the beads allows for more rapid isolation of the analytes than planar arrays of other assay methods2 Microfluids are implemented with the beads in order to both treat the sample and detect the target molecules.1 Fluorescent dye can be added as an indicator; the strength of fluorescence of the beads can be correlated with the concentration of the analyte.2 The device can be modified from a chemical processing unit to a cellular processing unit by replacing the panel with beads with a polycarbon membrane which acts as a filter at a larger scale than the chemical processing unit with beads.2 The membrane-based cellular processing can be used for cell counting and typing.3

The McDevitt lab also examines biomarkers, analytes and the conditions that they indicate. The PNBCs can already be applied to a wide array of analytes: pH, electrolytes, short polypeptides, metal cations, sugars, biological cofactors, cytokines, toxins, proteins, antibodies, and oligonucleotides.1 A PNBC can be implemented with saliva to diagnose acute myocardial infarction by using the biomarkers C-reactive protein, myoglobin and myeloperoxidase.4

The field of nanochips shows a lot of promise in all of its medical applications and the effect it could have on healthcare. The PNBCs are shown to have applications in HIV monitoring, chest pain diagnosis and gynecological cancer screening.6 The programmable nano bio chips have potential cancer and cardiac applications.1 The use of the PNBCs with the Electrocardiogram (ECG) is shown to be more reliable than ECG alone when diagnosing cardiac abnormalities. 4 The modular design gives it the ability to apply to new tests and increased interest in the nano-bio-chip will lead to progress in all diagnostic research.1 Improvements in microchip production will allow for even smaller, less invasive biochips and decrease in material costs are also to be expected.2 The nanochip achieves large effects even at nanoscale.1 The PNBCs have global implications because an affordable, mass-produced clinical test could revolutionize diagnosis worldwide.2 The PNBC is self-contained analysis method meaning that it can be used for diagnosis even in underdeveloped areas lacking laboratory supplies. A PNBC designed for HIV detection is particularly needed in developing nations.

References

1. Jokerst, J. V.; Floriano, P. N.; Christodoulides, N.; McDevitt, J. T.; Jacobson, J. W.;Bhangwandin B. D. Programmable Nano-Bio-Chip Sensors: Analytical Meets Clinical Analytical Chemistry. 2010, 82, 4533-4538.
2. Jokerst, J. V.; McDevitt, J. T. Programmable nano-bio-chips: multifunctional clinical tools for use at the point-of-care Technology Report: Nanomedicine. 2010, 5, 143-155.
3. Jokerst, J. V.; Camp, J. P.; Wong, J.; Lennart, A.; Pollard, A. A.; Floriano, P. N.; Christodoulides, N.; Simmons, G. W.; Zhou Y.; Ali, M. F.; McDevitt, J. T. Nano-Scale Control of Sensing Elements in the Programmable Nano-Bio-Chip Small. 2010, 1-41.
4 Floriano, P. N.; Christodoulides, N.; Miller, C. S.; Ebersole, J. L.; Spertus, J.; Rose, B. G.; Kinane, D. F.; Novak, M.J.; Steinhubl, S.; Acosta, S.; Mohanty, S.; Dharshan, P.; Yeh, C.; Redding, S.; Furmaga, W.; McDevitt, J. T. Clinical Chemistry. 2009, 55, 1530-1538.
5 Jokerst, J. V.; Raamanathan, A.; Christodoulides, N.; Pollard, A. A.; Simmons, G. W.; Wong, J.; Gage, C.; Furmaga, W. B.; Redding, S. W.; McDevitt, J. T. Nano-biochips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels Biosensors & Bioelectronics. 2009, 24, 3622-3629.
6 Jokerst, J. V.; Bhagwandin, B. D.; Jacobson, J. W.; McDevitt, J. T. Clinical applications of a programmable nano-bio-chip Clinical Laboratory International. 2009, 6, 24-27.

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