McDevitt Research Group: Research
McDevitt Lab Update
A major missing link in healthcare today is the absence of the Internet of Biomarkers (IOB); that is, consumer-facing clinical testing capabilities with intuitive and motivating interfaces accessible to individuals, pharmaceutical scientists, and care-providers. While numerous physical silicon-transducers (accelerometers, gyroscopes, GPS) are already integrated into smart phones, one extreme deficiency today is the lack of health-connected biomarker measurements. Indeed, up to 70 percent of current medical decisions are made using diagnostic tests performed in traditional health care settings, using phlebotomists, remote laboratories, and delayed reporting. This inefficient flow of diagnostic information stifles arrival of exponential medicine. Likewise, for patients to actively manage their own wellness, we must surmount this biomarker technology gap.
The McDevitt Lab at NYU is now developing the Cardiac ScoreCard (“Best Scientific Advances Award” by the Science Coalition, “Best of What's New Award” by Popular Science, “AACC Wallace H. Coulter Lectureship Award-2016”) that provides capabilities of assessing early risk as well as monitoring late-stage disease progression for heart attack and heart failure patients. These biomarker-driven tests have the potential to reduce costs radically and decrease wait times for patients in need of regular health monitoring. Expanding capabilities of consumer electronics, big data analytics, and web-aware sensors can create powerful cloud-connected diagnostic instruments for personalized wellness tracking, monitoring and feedback, and behavior modification. In translating information from the IOB fused with the IOT, such information-rich resources have potential to improve in an exponential manner developments related to drug discovery, health policy while at the same time allowing for new options for personalized wellness management.
Despite the remarkable advances in the development of miniaturized sensing and analytical components for use in a variety of biomedical and clinical applications, the ability to assemble and interface individual components in order to achieve a high level of integration in complete working systems continues to pose daunting challenges for the scientific community as a whole. The McDevitt laboratory has developed previously a number of miniaturized sensor concepts and methodologies that are suitable for a variety of important application areas such as clinical, environmental, bioterrorism, humanitarian and saliva-based diagnostic tools.
Over the past five decades, the microelectronics industry has sustained tremendous growth and has become what is arguably the most dominant industrial sector for our society. The electronics industry has spawned compounded annual growth of over 50% over this extended time period. This industry has touched almost every aspect of our modern lives through the development of personal computers, portable communication devices, various consumer electronics, navigation tools, imaging devices, etc. The availability of powerful microfabrication tools based on photolithographic methods that can be used to process these devices in highly parallel manner has led to this explosive growth.
Recently, it has become clear that the electronic industry will face new and significant challenges as component device feature sizes shrink into the nanometer size regime. However, with the challenge here comes the opportunity to develop a number of fascinating new sensors and devices using nano meter sized building blocks. The ultimate applications to be derived from such interdisciplinary efforts are likely to occur for the sectors in the life sciences and in the areas related to the health industries. Challenges with spiraling health care costs associated with cardiovascular disease, cancer, and diabetes, the global HIV crisis, and environmental and homeland defense areas all provide strong motivation for the creation of a bridge between microelectronics, nano-engineering and the health sciences.
Despite the remarkable advances in the development of miniaturized sensing and analytical components for use in a variety of biomedical and clinical applications, the ability to assemble and interface individual components in order to achieve a high level of integration in complete working systems continues to pose daunting challenges for the scientific community as a whole.
Lessons learned from the microelectronics and computer-software industries provide inspiration for what may be gained from the marriage of microelectronics and in vitro diagnostics areas. Indeed, there are some interesting parallels between the current state of medical devices, in particular, in vitro diagnostics, and the evolution of software and microelectronics industries. While medical tests have traditionally been completed in central laboratories that are filled with specialized equipment and trained technicians, there is currently a trend to complete more and more tests using portable instrumentation. Indeed, the point of care medical device area represents now the fastest growing sector of in vitro diagnostics. At some level, this evolution of medical diagnostic testing follows the same pathway the computer industry took where initial work stations were dedicated to single tasks. Over time, the computer became programmable and portable to the point where "personal computers" have evolved with high degree of task flexibility. Clearly, the availability of portable medical devices that could be tailored for "personal medical exams" using noninvasive diagnostic fluids such as saliva would have a profound influence on the way medical testing is practiced.
The ability to assemble and interface individual components in order to achieve a high level of integration in complete diagnostic devices continues to pose a daunting challenge for the scientific community as a whole. Even more difficult is the prospect of creating a modular standard "assay operating system" that can be adapted in a simple and rapid manner to new assays. Towards this goal, the McDevitt laboratory has developed previously a number of miniaturized sensor concepts and methodologies that are suitable for a variety of important application areas. Here, a system based on a micro-bead array wherein micro-etched pits within a silicon wafer are populated with a variety of chemically sensitized bead "micro-reactors." Created with many of the same microfabrication methods popularized by the electronics industry, such flexible sensor systems can be described as “chemical processing units." Developed initially as an "electronic taste chip" (ETC) system, this LOC-based sensor platform has been adapted now for a broad range of analyte classes including pH, electrolytes, metal cations, sugars, biological co-factors, toxins, proteins, antibodies, and oligonucleotides.
The ability to synthesize beads in our lab allows us the freedom to tailor certain variables such as bead size and porosity which helps us further optimize our assay development efforts.
The McDevitt lab has established rigorous procedures developed over a decade to define customized bead microreactors that service numerous clinical applications.
These beads have been customized to complete numerous classes of tests with reduced assay time and yet yield high performance.
Homogeneous agarose beads are prepared by emulsifying a 2% agarose solution. An overhead stirrer is used to create the emulsion at a speed that results in beads within a desired size range. Moreover, the beads are collected and sieved using a commercial sieve shaker to specifically acquire beads in the 250-280 μm fraction.
Agarose beads are then activated by taking them through crosslinking and glyoxylation chemistries. The glyoxal activation efficiency is tested using Schiff's reagent in which a change in color from clear to dark pink indicates aldehyde reactivity. Once reactivity is confirmed, the beads are ready for antibody conjugation through reductive amination.
The successful implementation of bead-based microreactors is instrumental in developing assays using the McDevitt LOC platform. Commercial beads have shown to be less than effective as there are inconsistencies in size, shape and thus, in reactivity when used in the assay development process. For this reason, agarose beads are synthesized, activated and tested at the McDevitt lab.
Biomarkers are the key indicators that the Bio-Nano-Chip is programmed to detect.
Our challenge is to move the dial in healthcare from illness to wellness. We are unlocking the path through technology and innovation to determine which biomarkers are linked to specific illnesses. We must better detect, diagnose and monitor diseases while improving speed, accuracy and affordability.
At the McDevitt Lab, we "begin with the end in mind." For our research efforts, this means developing a pipeline to move the Nanotechnology from the lab at Rice University’s BioScience Research Collaborative into the hands of clinicians at the Texas Medical Center across the street as well as clinicians across the world. The McDevitt Lab will be the first in medical microdevices to create viable bridge from the bench to the bedside.
Keys to your health status
Today most diseases are diagnosed too late when the costs are extremely high. Biomarkers have the potential to see into the future and allow us to capture diseases before clinical symptoms show up.
Biomarkers are the keys that unlock information about our health and wellness status. They allow us to see behind these doors that today are locked for most diseases.
For the diabetic patient blood glucose serves as a biomarker that inform the patient as to their ability to control blood sugar. If you are diabetic you may monitor your blood sugar a dozen times a day. You keep the blood sugar in a safe range and keep you body more healthy.
If you are a women with ovarian cancer, you monitor you CA125 level. If you are HIV positive, you follow your CD4 counts.
These biomarkers are like molecular thermometers telling us if we are in a healthy stage or moving in the direction of illness.
Here in the McDevitt lab we test the patient samples for the presence of various disease biomarkers.
These cellular samples could be in the form of blood, saliva, brush biopsies from the cheek or tongue.
The selection of biomarkers will vary depending upon the disease. The level of expression of the biomarkers will change according to the stage of the disease
All the cellular testing is done using the Lab-On-A-Chip platform
Following the assays, are the cytomorphometric assessments and the measurements of biomarker expression profiles.
The cytomorphometric assessments will focus on cell morphometric data, such as cell size, cell volume, nuclear size, and the nuclear/cytoplasmic ratio, whereas the biomarker expression assessments, which will use fluorescence immunostaining of both cell surface and intracellular tumor related antigens.
Computational fluid dynamics (CFD) is a powerful simulation tool that uses numerical methods and algorithms to solve and analyze fluid mechanics systems. By leveraging on the basic governing multiphysics processes of chemistry, biology, and physics, CFD serves as a predictive tool to model microfluidic immunoassays.
In designing microfluidic platforms, CFD serves as a tool to quickly analyze multiple designs to determine optimal channel geometries without the laborious need to manufacture fluidic cards, use of expensive reagents, and allocation of trained personnel's time. CFD also serves as a validation tool for experimental data of analyte binding within highly sensitive porous bead based immunoassays. In many cases, analysis of computational systems provides insights to questions that cannot be directly measured experimentally.
Advanced strategies to acquire, extract and analyze the signals produced in both the bead-based and the membrane-based platforms are crucial to ensure efficient and accurate assessment of key measurements such as biomarker presence, levels, or concentration, as well as biomarker expression and cytomorphological parameters on cellular materials.
Custom-based algorithms based on regional pixel analysis serve to transduce the complex optical signals captured by a CCD camera in an automated manner, in single as well as batch processing. Chemical and biological signals are transformed into digital and analog values and recorded in a database. User interface environments are created to efficiently (quickly and easily) manipulate large data sets, and provide advanced graphical and plotting snapshot capabilities, typically only encountered in high-end mathematical software. Advanced multi-variate analysis methods are evaluated for data mining and model development to identify the best candidate panels of biomarkers and parameters that display the highest clinical sensitivity and specificity, i.e. those that are best able to discriminate between disease and health status of various stages of disease progression.
Through 15 years of sustained activities in the area of medical microdevices, the McDevitt Lab has developed a series of programmable bio-nano-chip (p-BNC) sensors that are suitable for complex analysis. There are two major classes of sensor ensembles here developed as follows:
- Bead-based devices which are suitable for soluble chemistry analysis
- Membrane-based structures that are ideal for cellular analysis
Both these devices work within the same platform.
The McDevitt lab has employed a variety of fabrication methods to create the p-BNC. Methods include photolithography, wet etching, thermo-bonding, soft-lithography, xurography, hot-embossing, and injection molding. Some of the materials used in the creation of these p-BNC structures include are silicon, glass, polymers, and thermoplastics.
Translational Research Facilitated with Bio-Nano-Chip Systems
While nanotechnology promises to revolutionize medicine in the 21st century, there remain severe challenges with respect the integration of functional systems into cost-effective health treatment and management modalities.
Over the past decade, the McDevitt laboratory has sustained diligent efforts to move above and beyond the traditional academic endeavors with publications and presentations as the end goal into the regime of delivering research and clinical tools for use in important applications of societal interest. See Movies.
These efforts have resulted in:
1. The development of portable HIV immune function tests for use in resource poor settings;
2. The creation of new cardiac screening tools;
3. The development of next generation cancer diagnostic aids;
4. A new program initiated to develop the next generation of diagnostic chips suitable for trauma applications;
5. With funding from NIDCR-NIH Rice University launches a new clinical trial with Baylor College of Medicine for the purpose of validating salivary biomarkers for heart attacks;
6. Rice University wins NIDCR-NIH funding for oral-cancer test: Grand Opportunity grant funds rapid saliva test using lab-on-a-chip;
7. McDevitt lab launches the “Texas Cancer Diagnostics Pipeline” with funding from CPRIT.
These translational efforts strive to use the tools of nano science and engineering in an effort to improve the quality and accessibility of health care on a global scale.
With the move to Rice University in July of 2009, the McDevitt laboratory will secure access to the world’s largest medical complex with the aim of creating for the first time an effective bridge between medical devices and microfabrication approaches. This leadership position in the area of bio-nano-chip will allow for the development of powerful diagnostic aids that are affordable and accessible to all humanity.
Development of a Lab-on-a-Chip System for Saliva Based Diagnostics
Scope: The McDevitt group’s role for this joint program that spans five research groups is to develop new methods for measurement of saliva-based analytes using microfluidic devices.
Grant number: 1U01 DE017793-01 Development of a Lab-on-a-Chip System for Saliva Based Diagnostics
Development of a Lab-on-a-Chip System for Saliva Based Diagnostics
Scope: Building on the biomarker discoveries made for the heart attack test and the momentum gathered from the parent U-01 program, the clinical study tasked here aims to validate a multiplexed salivary biomarker panel for the screening of AMI in the emergency room setting.
Grant number: 3 U01 DE017793-05S1
Monitoring of Oral Cancer Patients Using Novel Lab-on-a-Chip Ensembles
Scope: The development of a minimally-invasive brush biopsy test for oral cancer diagnosis (no scalpel biopsy would be required) that when combined with a novel microchip can be performed in clinics or dentist’s offices with results that are available in a matter of minutes (within visit).
Grant number: 1 RC2 DE020785-01
Texas Cancer Diagnostics Pipeline Consortium
Scope: Through this novel program, efforts are directed toward the development of a platform that can be used to accelerate the release of new cancer diagnostic tests and screening devices in the state of Texas. Through the unique partnerships here assembled an infrastructure will be developed that serves to span the essential areas of biomarker discovery, biomarker validation and clinical implementation with the goal of achieving technological innovation, reduced health care costs and improved healthcare outcomes. These efforts are unique in scope in terms of their capacity to combine nano science and engineering, state-of-the-art imaging methods, microfluidics concepts for sample processing and multiplexed biomarker panel analysis for the development of integrated test ensembles suitable for screening and diagnostic testing for oral, prostate and ovarian cancers.
Advanced Nano-Bio-Chips for Saliva-Based Drug Tests at the Point-of-Arrest
Scope: RoadsideBNC drug tests to be developed with this Home Office Scientific Development Branch (HOSDB) program promise to serve as important tools for police officers to prosecute drugged driving. The BNC roadside drug tests are projected to save time and simplify the enforcement procedure by avoiding the need to take the suspected drugged drives to a police station, or health care facility, for testing. Completion of the proposed work promises a more convenient, cost-effective and comprehensive drug screening approach that may be applied for roadside testing of drivers at the point of arrest (POA).
Creation of NanoHealth Center for Early-Response to Acute Trauma and Injury
Scope: The McDevitt group’s role for this joint program that spans two research groups is to develop new methods for measurement of acute trauma biomarkers in urine samples.
Dates: 9/1/09 – 8/31/11
PI: John Holcombe
Development and Deployment of CD4 Counting Microchip Systems for Use in Resource-Scarce Settings
Scope: This program served to expand upon the successful demonstration of the highly promising chip-based CD4 counting technology developed by the University of Texas at Austin and Harvard Medical School. With this accelerated effort, the already established and productive collaborative program between the Harvard Medical School Division of AIDS and the Chemistry/Biochemistry Department at the University of Texas at Austin was expanded to target the short-term development and deployment of important CD4 diagnostic instrumentation that is suitable for immediate use in resource-scarce settings.