• OLA-Simple

    Develop a point-of-care HIV drug resistance test to assist clinicians in identifying most effective antiretroviral treatment (ART) plan

    Background and Significance

    Most HIV-infected individuals live in low-/middle-income countries where access to well-equipped labs is limited. OLA is an economical assay for detecting drug-resistant HIV, however, the current laboratory test is too complex to be adopted in low-resource settings. To expand access, OLA must be re-engineered into a simple point-of-care format.

    Current state of OLA-Simple

    Several areas of the OLA are being re-engineered, using sophisticated chemistry and physics principles to enable a sensitive, easy-to-use, and inexpensive test:

    1) Dried reagent platform for long-term stability in sub-optimal conditions

    2) Isothermal molecular assay to eliminate the need for expensive equipment

    3) On-paper multiplexed detection of drug-resistant HIV

  • Lab in a phone call

    Develop technology that enables cellphone audio to control flow and detect analytes in a microfluidic channel, both essential components of analytical test

    Vision - Flow control

    Network of microfluidic channels that respond selectively to cellphone audio tones can be used to perform sequential delivery of reagents, a requirement to perform complex bioanalytical assays.

    Vision - Analyte detection

    Resonance frequency of a microfluidic channel with deformable features is related to the physical properties, such as density, viscosity, or compressibility, of the fluid in the channel. Analyte-mediated changes in these properties can be measured as shift in resonance frequency using tiny optical sensor. Coagulation and catalase-based bubble formation assays are being investigated

    Current state

    Top left shows a series RLC resonant device containing a channel ending in a deformable diaphragm and driven by a piezo buzzer on the other end. Oscillating flow magnitude and phase in the channel is measured for a range of actuation frequencies. At resonance, flow magnitude is maximum and flow phase is zero compared to actuation signal, just like in a classic electrical resonant circuit.

  • TB urine test

    Detection of tuberculosis cell-free DNA (cfDNA) in urine by sequence-specific capture

    Vision

    A quick and simple TB urine test for all patients

    TB is the leading cause of infectious disease death worldwide, largely due to insufficiencies in its diagnosis. We hope to enable TB diagnosis across a wider range of patients (particularly children and HIV co-infected individuals) by testing urine, rather than sputum. Urine contains short, cell-free DNA (cfDNA) fragments generated from dying TB bacteria. By pairing sequence-specific hybridization capture of cfDNA with amplification designs for ultra-short targets, our goal is to improve the clinical sensitivity of TB diagnosis from urine. In the future, we aim to develop a TB urine test simple enough for use in low resource settings.

    Current state

    Current state: Assay optimization, clinical testing, and translation to simplified format​

    Our hybridization capture method is capable of reliably detecting down to 10 copies of a 25 bp cfDNA fragment per mL of urine, an improvement over both the sensitivity and lower fragment length limit of alternate silica-based methods. We are now testing hybridization capture with clinical samples from TB ​patients, while continuing assay improvements to push the lower limits of cfDNA detection in urine. We have begun moving towards a simplified format by integrating dried reagents, less costly streptavidin substrates, and isothermal amplification into the hybridization capture assay.

  • Acute HIV detection

    Point of care diagnostic for acute HIV in low resource settings

     

    Significance and Background

    Providing a diagnostic device for HIV to developing areas according to WHO criteria for diagnostics

    WHO require point of care devices to fit ASSURED criteria: Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Delivered to those who need it. Our lab is working on detection of the HIV-associated p24 antigen, which allows for detection up to ten days prior to detection by human host antibodies; we do not have to wait for the infected patient's immune response to detect HIV.

    Current state

    Preliminary Testing

    Our first prototype for the device was printed last spring. Currently we are doing testing flow properties and developing the p24 assay in a bench format. This is all in preparation of actual device testing and implementation of dehydrated chemicals in the coming months.

  • Cellphone-based coagulation monitor

    Development of technology that enables patients on anticoagulants to use their cell phones and disposable microfluidic chips to monitor their coagulation activity

    Vision

    Improving access to coagulation monitoring for the millions needing it

    Ubiquitous technology to allow patients to avoid having to go to labs to perform clotting tests. Instead, they can conveniently use their cell phones and disposable microfluidic chips—allowing them to save money and obtain faster results.

    Current State

    Models and Simulations

    We are currently modeling our system in MATLAB to study the correlations between resonant frequency changes and fluid physical property changes. Preliminary experiments have been performed using chitosan gelation to simulate blood coagulation.