PaperSpray Ambient Ionization
Researchers at Purdue University have developed two enabling technologies which have the ability to drive a sea change in the way chemotherapeutic agents are administered and monitored within oncology. These technologies will enable the creation of a Point of Care system which will provide comparable Therapeutic Drug Monitoring results to remote laboratory analysis within minutes of a miniscule blood collection taken at the point of care. The system consists of a capital unit and a disposable cartridge which performs quantification based on mass spectrometry. The first key technology is miniaturization of mass spectrometers which has been extensively researched at the Aston Laboratory headed by Dr. R. Graham Cooks, Henry B. Hass Distinguished Professor of Chemistry. The latest version of the miniature mass spectrometers (Mini-MS) produced in this lab is a fully functional portable unit the size of a shoebox weighing approximately 8 pounds. In collaboration with Dr. Zheng Ouyang, Assistant Professor of Biomedical Engineering and Electrical & Computer Engineering, a second key technology, known as the PaperSpray Ambient Ionization method was successfully developed. The PaperSpray method allows direct mass spectrometer analysis of blood samples without any special sample preparation. The combination of Mini-MS and PaperSpray results in a cost-effective, rapid delivery of TDM results at the point of care.
Proof of concept studies and validation of PaperSpray to perform TDM measurements have been completed. Results of these studies demonstrated the capability of the assay to accurately measure circulating drug levels well within the performance standards set by the FDA for bioanalytical assays (“Guidance for Industry – Bioanalytical Method Validation” CDER, May 2001). An engineering prototype of the POC TDM system has been developed and plans to develop a commercial prototype have been outlined. As an intermediate step to the point of care device, development of a PaperSpray ion source which enables rapid analysis of a blood sample using less than 20 micro liters on existing mass spectrometers is underway. The PaperSpray ion source development has been completed as of June, 2011.
Point of Care Therapeutic Drug Monitoring
Therapeutic Drug Monitoring, the process of measuring active drug levels in a patient’s bloodstream, is a practice commonly coupled to drugs with narrow therapeutic windows. For such drugs, it is important to maintain the dose above the futility level, and below the toxic level. Current methods for performing TDM are both laborious and expensive. The typical scenario involves blood drawn from the patient and sent to a laboratory for processing. Several rounds of sample processing are typically needed prior to the drug quantification assay, all requiring highly trained personnel to perform. Results generated from the laboratory are then entered into the system. The whole process ranges from 1-2 days up to a few weeks. This current practice of performing TDM is prohibitive to the use of TDM within Oncology. As a result, oncologists rely on a dosing regimen known as Dose to Toxicity, i.e. patients are given more and more drugs until they experience intolerable toxic side effects. The development of a Point of Care Therapeutic Drug Monitoring system (POC TDM) holds the promise of creating a new paradigm in the administration of chemotherapeutic agents, dubbed Intelligent Dosing by a group of key opinion leaders in Oncology.
The concept of Intelligent Dosing is focused on improving the decision making process during dose adjustment. As stated by a leading oncologist, clinicians currently make dose adjustments blindly. In today’s current practice, the dose is simply increased until the full dose is reached, and lowered on the incidence of toxicity (side effects) without considering the circulating drug level within the patient. The importance of measuring the circulating drug level is because each patient’s metabolism is highly variable and the ability of each patient to metabolize the administered drug will vary greatly. As a result, for the same administered dose, the amount of active drug in the patient’s body can differ significantly between patients. The idea of using the circulating drug level as a benchmark, i.e. TDM results, in guiding dose administration has been discussed for decades but has failed mainstream adoption due to the current methods of performing TDM which are costly and time prohibitive.
The initial target market for the POC TDM device is oncology. Specifically, five initial drug targets have been identified which are currently used to treat breast and colon cancers. The selection of these drugs was guided by a clinician round table attended by seven key opinion leaders (5 oncologist and 2 clinical pharmacologists) from highly acclaimed cancer centers including MD Anderson, Dana-Farber, Cleveland Clinic, St. Jude Children’s Hospital, and University of North Carolina’s Institute for Pharmacogenomics and Individualized Therapy. Potential for the initial target market which focuses on several large metro areas with renowned cancer centers is estimated at $600M+. Rapid expansion of market size is expected through utilization of the drug in other cancer types as well as the addition of other drugs and smaller metropolitan areas.
Continued development of the POC TDM system will require $2.4M to fund building of the commercial prototypes for use in clinical studies. Concurrent development will include the development of the assays for the identified initial drugs. The timeline for this next phase of development is 15-18 months.
Figure 1. Artist rendition of POC TDM System
For additional information please contact:
Steve Mogensen
Managing Director
Alfred Mann Institute for Biomedical Development at Purdue University
207 S. Martin Jischke Dr.
Hall for Discovery and Learning Research (HDLR) Suite 103
West Lafayette, IN, 47907
smogensen@amipurdue.org , 765-494-8316
