Portable Bioanalysis System
From raw sample to molecular results in minutes: The Sentinel Nucleic Acid Analysis System offers portable, real-time diagnosis of health conditions.
Our understanding of human biological systems has increased dramatically over the last 20 years, providing the potential for significant improvement in personalized medicine. Even with recent advances, however, diagnostic tests are still conducted much as they were 50 years ago: Samples are typically processed in centralized laboratories by technicians who cannot provide results until hours or even days later. In many cases, such as with bacterial or viral respiratory illnesses, delays can mean that doctors must make clinical decisions before a diagnosis is known.
A portable biological analysis system that could identify pathogens and conduct routine health status monitoring and environmental monitoring in minutes would enable rapid intervention at the point of care. Currently, no commercial nucleic acid bioanalysis instruments can perform diagnostic tests outside of Clinical Laboratory Improvement Amendments (CLIA)-regulated laboratories. The few integrated analysis systems appearing in the research literature are years away from commercialization.
To fill this gap, SRI is developing the Sentinel Nucleic Acid Analysis System. Sentinel is a portable, integrated, rapidly reconfigurable, automated biodetection hardware system that performs “sample-in to answer-out” field analyses such as:
- Bacterial agent detection
- RNA virus detection
- mRNA/microRNA detection
The system could be further developed to diagnose health conditions such as flu, dengue fever, HIV, and more.
Sentinel’s consumable microfluidic cartridge has been transitioned to a contract manufacturer for limited-rate initial production in an ISO 13485-compliant quality management system.
How It Works
- Improved sensitivity: Microarray-based detection does not require sample splitting for multiplexing
- Order-of-magnitude improvement in multiplexing over most platforms
- Rapid labeling and amplification (40 cycles in as few as 12 minutes) from proprietary PCR module
- Portability due to small size (<5 lb and about the size of an index card box), allowing movement of diagnostic capability to the patient rather than the patient to the diagnostic capability
- Rapid configurability for other assays provided by a single microfluidic card (iMFC) breadboard (similar to the way peripheral devices are added to computer motherboards to provide application-specific functionality).
Key Features and Performance Parameters
Ease of Use
- Automated sample processing: The iMFC can be loaded with a raw sample directly from the sampling device; no sample preparation by the user is required.
- Small size: The entire system is operated by a laptop or mobile phone.
- Modular design: Modules with various functions or different reagents can be interchanged to build the card that is specific to the assay of interest.
- Different sample matrixes: The Sentinel system is currently designed for environmental samples, but is being configured for nasal swabs, virus transport media, and blood
Assay Flexibility, Specificity, and Speed
- Detection of multiple targets: The microarray chips can detect various targets in a single sample (e.g., a single chip can differentiate all 57 adenoviridae from a single PCR amplicon).
- Real-time DNA hybridization: Real-time kinetic measurements and dynamic temperature control of the sample on the microarray provide improved assay specificity and reduced time to answer.
- Fast polymerase chain reaction (PCR): Rapid PCR amplification significantly reduces assay labeling and amplification.
Manufacturability and Cost
- “Motherboard” iMFC concept: The main iMFC (“motherboard”) is generic; the lower-cost modules define the application. Once fabricated, the same cards can be used for a wide range of applications, thereby reducing cost and development time.
- Established roll-to-roll manufacturing: Completed process development of a high-volume manufacturing approach that can produce >1M iMFC motherboards per year.
Hand-held Analyzer Specifications
- Dimensions: 6.25 W x 4.625 D x 5.125 H
- Weight: Less than 5 lb
- Fully contained system with
- Microfluidic card actuation
- Rapid PCR thermal cycling
- Compact microarray detection optics
- Automated hybridization processing and analysis
- Compatible with different assays using different microfluidic modules
- Wall- or battery-powered
This system was developed in part by research funded by the U.S. Department of Defense. The views, opinions, and/or findings contained in this article/presentation are those of the author(s)/presenter(s) and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.
Approved for Public Release, Distribution Unlimited