331 Development of a Biosensor-Based Core Needle Tumor Biopsy Device

Fast-Track proposals will be accepted.

Number of Anticipated Awards: 3-5

Budget (total costs, per award):
Phase I: $225,000 for 9 months;
Phase II: $1,500,000 for 2 years

It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.

The deadline for receipt of all contract proposals submitted in response to this solicitation has expired. It was: November 25, 2013 by 4:30 p.m. ET.

Summary:

Analysis of dynamic biomarkers in tumor biopsies is being performed with increasing frequency to help physicians in diagnosis, selecting and assessing treatment, and understanding disease recurrence. Current biopsy techniques were developed to acquire specimens with sufficient numbers of malignant cells for histopathologic diagnosis. However, the tumor content of a biopsy specimen required for pathological analysis is much lower than what is required for molecular profiling of low prevalence mutations or biomarker quantification, which would aid in determining therapeutic options for the patient. Even with Positron Emission Tomography/Computed Tomography (PET/CT) or ultrasound guidance, current biopsy methodology may not yield specimens with sufficient tumor for molecular biomarker profiling. PET/CT and ultrasound methods lack the resolution to direct the biopsy needle into areas with high viable tumor content, resulting in a high failure rate of 25 – 50% due to the heterogeneity of tumor architecture within a biopsy area. The incorporation of biosensor technology into the tip of the biopsy needle, in conjunction with currently utilized imaging and ultrasound guidance, could increase the probability of sampling high tumor content areas through providing real-time feedback that identifies optimal regions for biopsy. Collection of high quality tumor biopsies with sufficient material for biomarker profiling is essential for full implementation of precision medicine for cancer patients. Biosensor/biofeedback devices designed to complement existing radiologic methods will improve current biopsy procedures by increasing viable tumor recovery, and thus, allow for a more thorough molecular assessment of patient tumors.

Project Goals:

The goal of this solicitation is to advance the development of biopsy needle-based biosensor technology that can determine regions of maximum tumor cellularity within the biopsy region. The biosensor technology should be designed for use in conjunction with current image-guided and biopsy devices to detect high tumor content regions, and provide real-time feedback that indicates to the radiologist where the needle should be placed for optimal sample selection. Real-time feedback from the tip of the biopsy needle to the physician should be based on visual, sensory, or chemical parameters.

Malignant transformation is associated with structural, genotypic/phenotypic cellular modifications, and biochemical changes in the extracellular environment, which consequently alters spectroscopic, metabolic and microscopic properties. The biosensor should be able to detect such alterations and extract information about the physiological and/or morphological properties in the biopsy region surrounding the needle that distinguish normal from malignant areas. Properties include, but are not limited to, measurement of redox potential, pH, extracellular matrix elasticity/stiffness, dielectric properties (electrical bio-impedance), glucose metabolism (anaerobic glycolysis), and various blood vessel parameters such as tissue color, microvascular saturation, blood volume fraction, bilirubin concentration, and average vessel diameter.

Phase I Activities and Expected Deliverables:

• Manufacture and optimize a needle-based biosensor device with the following features:
  
  1. adaptability for use with existing imaging/ultrasound needle placement methods and needle biopsy procedures.
  2. real-time signal generation indicative of physiological and/or morphological parameters that distinguish between tumor and non-tumor tissue, and if possible, between necrotic and viable tumor.
  3. does not significantly damage or change tissue biology in regions surrounding the needle placement site.
• Show preliminary proof-of-concept of the sensor-guided biopsy in a relevant animal model.
• Produce written methodology for the sensor manufacturing with quality assurance and control measures using the Standard Operating Procedure (SOP) template to be provided by NCI.
• Provide device and training in use to NCI. The device and associated methodology will undergo independent validation at NCI.

Phase II Activities and Expected Deliverables:

• Optimize the sensor design and performance for a clinical setting, and refine the manufacturing process.
• Show the feasibility of this novel technique to complement current radiologic and biopsy procedures.
• Demonstrate the performance of the device as designed and intended in fit-for-purpose studies in relevant clinical veterinary models (NCI will identify appropriate models during Phase I).
• Deliver to NCI final versions of the manufacturing methodology and Certificate of Performance using recommended templates (to be provided in Phase I).
• Provide at least one optimized device, technical support, and if requested, one on-site training session for NCI in order to perform independent validation.
• Provide to NCI staff two letters of commercial interest at the end of year 1, and two letters of commercial commitment to buy the developed product at the end of year 2.