This is a short list of some of the projects ongoing in the lab and in conjunction with our collaborators. Please contact us for more information about any of them.
Center for Future Technologies in Cancer Care (CFTCC)
Dr. Klapperich is the director of the CFTCC. Moving cancer treatments out of specialized centers and into local clinics or home care could significantly lower healthcare costs. Often patients have to travel large distances to receive treatments at cancer centers. In low resource settings in the developing world, there may not be any options for cancer treatment. Surgical treatments carry infection risks and in many places there are not enough surgeons to treat all of the patients in need. Technologies such as targeted ultrasound and light-based treatments could allow providers with less specialized training to treat more patients for less money. Tools for monitoring chemotherapy patients at home between treatments could eliminate travel and office visits. Mobile health strategies for collecting data about high-risk populations could lead to new interventions to directly impact cancer screening rates.
To address these issues, the Center is focusing on the identification, prototyping and early clinical assessment of innovative point-of-care technologies for the treatment, screening, diagnosis and monitoring of cancers. A major aspect of this effort involves assessing early stage technologies in terms of clinical needs, market demands, setting appropriateness and commercialization strategies. The integrated multidisciplinary team, consisting of engineers, clinicians, public health practitioners, and technology transfer experts, is currently evaluating technologies in various stages of development for suitability across a range of primary care and non-traditional healthcare settings. The Center is funded by a grant from the NIBIB to Dr. Klapperich.
A Rapid Instrument Free Molecular Diagnostic for B. Pertussis
Acute respiratory infections (ARIs) are the leading cause of death in children under five throughout the world. Both vaccination and early diagnosis are critical to appropriate treatments and preventing transmission. However, infants too young to be fully immunized are most at risk of contracting ARIs. Whooping cough alone, an infection due to Bordetella pertussis (B. pertussis), causes more than 300,000 deaths per year; 90% of which occur in developing countries . While easily treated with first-line antibiotics more than half of all infants infected with B. pertussis require hospitalization, even in the US . Because the initial symptoms of this bacterial infection are indistinguishable from viral ARIs, diagnosis based solely on clinical symptoms is impossible and many infants are not treated until it is too late. A low-cost POC test for pertussis would enhance detection coverage and enable early detection resulting in improved treatment outcomes and prevention of further transmission. We are developing a paper-based molecular diagnostic test for B. pertussis will detect this deadly respiratory infection at the POC. The test will be hand-held, disposable, and instrument-free. Ultimately, this work will develop a rapid molecular diagnosic platform that can be adapted to other diseases by simply altering the primer and probe targets in the isothermal amplification module. This work is funded by an F32 grant from NIAID to Dr. Jacqueline Linnes.
Helicase dependent amplification for simpler diagnosis of Human African Trypanosomiasis
Human African trypanosomiasis (HAT) is a highly neglected tropical disease. About 20 to 30% of HAT patients are left undiagnosed by laborious parasitological techniques. In the past decade only one molecular test; the Loop Mediated Isothermal Amplification has shown potential for use in remote disease endemic areas. Helicase dependant amplification (HDA) an isothermal test will be based on oligonucleotide sequences of conserved multi copy genes of human infective trypanosoma brucei sub-species. A single step HDA reaction will be coupled with a lateral flow readout. This work is funded by a subcontract from a grant to Dr. Claire Mugasa from Grand Challenges Canada.
POC Helicase Dependent Amplification of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
This proof-of-concept project is focused on the most abundant sexually transmitted disease (STD) pathogens: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). The scientific literature clearly shows that molecular testing is the most sensitive means of detecting CT and NG and the molecular CT/NG high throughput screening market is currently valued at over $300M/year. Moreover, CDC urges STD clinics to test patients with POC tests if health care workers suspect these patients are unlikely to return to the STD clinic to learn the results of the test. Unfortunately, there are no point-of-care (POC) CT NG molecular tests, and existing POC molecular testing systems like the GeneXpert are too costly for use in STD clinics. We are developing a low-cost POC molecular diagnostic system for instrument-free detection of amplification products. The device will incorporate a lateral flow strip as a means of detecting the presence or absence of nucleic acid amplification products by simple visual inspection. This work was funded by an STTR grant from NIAID to Dr. Klapperich and BioHelix, Inc.
Sample Preparation for a POC HIV Viral Load Test
This NIH funded project is a collaboration with Wave80 Biosciences (San Francisco, CA). We are working on viral RNA extraction from whole blood input samples. The goal of the project is to detect a semiquantitative viral load in HIV patients on drug therapy at the point of care. This work is funded by a subcontract to BU from Wave80 from the NIAID.
Development of a Near Real Time, Multiplexed Diagnostics for Viral Hemorrhagic Fevers
Hemorrhagic fever viruses such as Ebola, Marburg and Lassa are responsible for current endemic diseases in Africa and are classified as Category A biothreats by the CDC because of the high fatality that can be associated with these diseases and their low infectious dose. Because of the concern of the release of weaponized Ebola, Marburg or Lassa, simple and effective detection and diagnostics are essential. While there are several existing assays for diagnosing infection with these viruses, they involve significant biosafety considerations, as the assays are not closed system sample-to-answer systems. The goal of this project is to develop a proof-of-concept design for a self-contained diagnostic system for viruses that cause hemorrhagic fever. The basis for the diagnostic platform will be a light-based detector that will allow low-power, simple testing of patients that are potentially infected. The straightforward technology that is proposed here can be directly scaled to inexpensive large-scale production through the leveraging of existing telecommunications and computing manufacturing techniques. This project is funded by subcontract to Dr. Klapperich from a grant to Dr. John Connor by the NIAID.
POC Device for Sample Preparation Upstream of SERS Identification of Bacteria in Blood
When a patient arrives in an emergency room with clinical symptoms consistent with bloodstream infection, blood cultures are drawn and empiric antimicrobial therapy is given; the actual identification of the pathogen by the laboratory typically takes one or more days. In the absence of specific data on the identity and susceptibility of the pathogen at the time of presentation, the clinician is forced to choose broad-spectrum antimicrobial therapy to cover all possible causes of the suspected bloodstream infection. Unfortunately, such empiric choices can sometimes end up being either ineffective (in the setting of antimicrobial resistance) or unnecessarily broad (in the setting of a susceptible and easily treated organism), potentially increasing morbidity, mortality, and resultant health care costs . To address this need, the Fraunhofer Center for Manufacturing Innovation (FCMI) has developed a prototype identification system based on surface enhanced Raman spectroscopy (SERS). This work is funded by a subcontract to BU from a grant to Dr. Alexis Sauer-Budge at FCMI by the NIAID.