Funded Projects - 2012

Electrical system for the rapid detection of viable bacteria in blood cultures

About 18 million blood culture tests are performed each year in the US. Virtually every hospital has a blood culture unit, to conduct a test to ascertain the presence of viable microorganisms in blood. Blood stream infections can lead to inflammation that, if untreated, can progress to sepsis. More than 751,000 cases of severe sepsis occur each year in the U.S., out of which 383,000 (51.1%) require intensive care, and 215,000 (28.6%) are fatal. Because of the low concentration of viable bacteria present when symptoms are manifested and/or blood is drawn, and the presence of large amounts of human and bacterial DNA in blood, the standard clinical protocol calls for a three-step diagnostic process.

The first step, blood culture, is used to merely detect the presence of viable microorganisms. The second step is microbial identification, and the final step is antibiotic susceptibility profiling. The key clinical intervention, the administration of targeted antibiotic, can be accomplished only after step 2, microbial ID. However, while microbial ID typically takes less than one day, the bottle-neck to quicker diagnosis remains the first step (blood culture) that takes one to five days.

Our technology promises to reduce the time for blood culture to two to 24 hours, instead of the one to five days currently taken, thus saving an average of one to three days in this first step towards diagnosis and intervention. The technology has been licensed to ImpeDx Diagnostics. ImpeDx recently received a $2.9 million Small Business Innovation Research grant to continue development of the technology.

A microRNA-based molecular diagnostics platform, focused initially on monitoring lung cancer therapy

Lung cancer is the leading cause of cancer mortality; 160,000 people in the US and 1.2 million worldwide die from this disease each year. Lung cancer-derived circulating microRNAs are being investigated as a new type of biomarker for lung cancer early diagnosis. However, current methods including qRT-PCR and microarrays have limitations in accurate quantification of circulating microRNA.

In this project, the PI’s will advance the nanopore single-molecule sensor technology invented in the PIs’ labs into a sensitive and accurate microRNA assay that can be used as a cost effective non-invasive clinical screening test for early diagnosis of lung cancer. The system can also be used in assay of new biomarkers for all other types of cancers and other diseases such as heart disease, diabetes and even psychiatric disorders. The nanopore sensor can be adapted to detect any pathogenic DNA or RNA fragments, and detect a single nucleotide polymorphism and DNA methylation with many broad clinical applications including early diagnosis, prediction of cancer metastasis, monitoring of response to therapy, and detection of minimal residual disease.

Technology for producing superior ACL grafts by conjugating nanomaterials with acellular biologically derived tissue

There are approximately 350,000 ACL reconstruction surgeries per year which involve autograft or allografts and the acute care associated with ACL surgeries is estimated to be $6 billion annually in the US. Current problems experienced by many ACL reconstruction patients is joint instability caused in part by lack of cellular integration and remodeling, leading to deterioration of the graft.

The PIs have developed a patented technology where nanomaterials are conjugated to acellular tissue to provide a 3D tissue network that has enhanced remodeling and controlled degradation, promotes cellular in-growth, and provide good mechanical behavior. Our transformative technology utilizes a functionally graded nano-graft.

A photoacoustic instrument for depth profiling and imaging of a burn to aid wound management decisions and debridement

There are an estimated 500,000 cases of burn injury that require medical attention in the United States every year. This number gives rise to an estimated $4 billion annual cost. Early and accurate determination of burn depth is crucial in deciding which steps are taken to treat a burn wound. Currently, clinical observation, an inexact science, is the standard method for determining burn depth. Although it is an accurate predictor of full-thickness burns, it is only 50 percent accurate in the diagnosis of partial thickness burns. A method that could objectively determine the extent of burn damage would provide clinicians with a valuable tool in the monitoring and diagnosis of burn wounds.

Furthermore, if a depth profile of the wound were available such that necrotic tissue was differentiated from reversibly damaged or viable tissue, early and accurate excision of the burn wound would be possible, an important factor in the treatment of partial thickness burns. The principal investigators are developing a noninvasive method based on laser induced ultrasound to immediately and unambiguously determine burn depth so that precise excision can be performed. This guided precision will allow maximum preservation of subsurface epithelial structures that are responsible for healing.

Technology for capturing a parameter of the pupillary light reflex in infants and toddlers and determining its utility for earlier detection of neurodevelopmental disorders than is currently possible

The PIs are developing a new technology to address the clinical need of an objective and economical tool for early identification of neurodevelopmental disorders in children. Pupillary light reflex (PLR) is a simple functional neurological test that measures the pupil size changes in response to a short light flash. Recent experimental studies have shown that PLR can be applied to monitor the neurodevelopmental progress in children. However, current existing PLR devices have difficulties to be applied reliably in young children who cannot fully cooperate during the test.

The PIs are developing a PLR system that can be utilized in children and toddlers. Once successful, the proposed device will be the first viable tool for objective monitoring of a child’s neurodevelopmental progress. No other devices can provide such a simple and low‐cost examination of brain functions. This technology has been licensed to LifeSpan Behavioral Technologies. LifeSpan is currently using a crowd-funding model to continue development of the PLR System.