Personalized Medicine: Home Test Kit for Cancer

Transcription

1 Personalized Medicine: Home Test Kit for Cancer Joanne I. Yeh, Ph.D Associate Professor, Department of Structural Biology, University of Pittsburgh; Associate Professor, Department of Bioengineering, University of Pittsburgh; Director, X-Ray Crystallography Facility in the UPSOM & Department of Structural Biology ; Director, PCHPI X-ray Crystallography & Structure Determination Core.

2 Coordinated nanobiosensor We have created a novel coordinated nanobiosensor for ultrasensitive detection of cancer biomarkers. This biosensor technology produces a compact, handheld device for the automatic, rapid, and sensitive detection of cancer biomarkers in human serum and/or urine. This device can be used at the point of care or by a consumer, directly with little to no training.

3 A B Figure 1. (A) Schematic of a biosensor; (B) Scanning electron microscopy of the highly ordered carbon nanotube nanoelectrodes array and 3 D gold nanoelectrodes ensemble.

4 A B C Figure 2. (A): Finished three electrode cell. (B): Final chip after the PDMS microchannel is assembled with the glass substrate. (C): A PSA detecting prototype based on pointof care biosensor system.

5 A B Figure 3. The schematics of the coordinated biosensor based on gold nanoelectrodes ensemble (A) and carbon nanotube nanoelectrodes array (B) [1 5].

6 A B Figure 4. The 3 D structures of biolinkers. (A) PNA ; (B) PNA; and (C) peptide [6].

7 Application of coordinated biosensors The coordinated biosensor based device analyzes clinically significant disease biomarkers and will provide clinically relevant information to either inform a consumer or assist the physician and clinician in disease diagnosis, prognosis, treatment and recurrence.

8 Table 1. Some biomarkers for determine relative cancers [7]. Biomarker Prostate specific antigen Alpha fetoprotein, carcinoembryonic antigen Carcinoembryonic antigen, CA19 9, CA24 2 Carcinoembryonic antigen; CA72 4, CA19 9 Squamous cell carcinoma antigen Carcinoembryonic antigen, CA19 9, squamous cell carcinoma antigen, CYFRA21 1, Neuron specific enolase Carcinoembryonic antigen, CA15 3, CA125 Alpha fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin, CA125 Human chorionic gonadotropin, squamous cell carcinoma antigen Cancer Prostate cancer Liver cancer Colorectal and pancreatic cancer Gastric carcinoma Esophagus carcinoma Lung cancer Breast cancer Epithelial ovarian tumors Trophoblastic cancer

9 Prostate cancer diagnosis Here we show an application of the coordinated nanobiosensor for detection of a prostate cancer biomarker prostate specific antigen (PSA). At present, there is no available curative therapy once the disease spreads beyond the limits of the organ. The best way to control and decrease mortality rates from prostate cancer is to detect the disease at an early stage, while it is localized to the prostate. Measuring the level PSA in blood is currently the only FDA approved clinical test for diagnosing and monitoring the disease. The serum PSA has been approved as the most reliable clinical tool for diagnosing and monitoring the disease. Total PSA levels significantly increases in serum during prostate cancer and a level above 4.0 ng ml 1 indicates high probability of prostate cancer [8].

10 Figure 5. Prostate gland, prostate cancer and PSA testing by immunostrip tests: (A) Control, (B) t PSA, (C) f PSA lines [9].

11 Benefits from PSA coordinated nanobiosensors PREAPPROVED: The U.S. Food and Drug Administration (FDA) has approved the use of a PSA test to help detect prostate cancer in men 50 years of age or older [8]. PROACTIVE: The FDA has also approved the use of the PSA test to monitor patients who have a history of prostate cancer to see if the cancer has recurred. If a man s PSA level begins to rise, it may be the first sign of recurrence and early detection can lead to better prognosis and decreased health care costs [8]. ONGOING NEED: The health care institutions, physicians, and patients can diagnose prostate cancer or evaluate whether the cancer has returned after prostate surgery.

12 Advantages of coordinated nanobiosensors over existing tests Simple Inexpensive Fast Reduced size Accurate High sensitivity Without sample preparation and reagent handling Meet the need of routine clinic and home testing

13 Table 2. The features and limitations of current PSA testing with large instruments. Features Testing at dedicated laboratories Low detection limits Proven reliability Limitations Requirement for sample transportation to dedicated laboratories Several weeks from testing to results High cost Table 3. The features and limitations of commercial immunostrips for PSA testing. Advantages Disadvantages low cost lack of sensitivity ease of use

14 Figure 6. The correlation between PSA biosensors and the ELISA method [10].

15 Potential market Prostate cancer is a deadly disease and a major cause of death for men between the ages of 55 and 84 [8]. It accounts for approximately 10 percent of all deaths from cancer. It is estimated that 192,280 men will be diagnosed with and 27,360 men will die of cancer of the prostate in 2009 in United States [8]. If we define the market as those men over the age of 50, and only sell monthly test kits to each person at $10/kit, the potential market size is over $4.5 BILLION/YEAR in the US alone. We believe the cost factor is highly advantageous and, in conjunction with the simplicity of design and robustness of performance, these one step diagnostics will be especially useful in rural areas in the US and in less developed countries.

16 Greater Potential Market only need to identify biomarkers; some already identified Men 294,120 Women 271,530 Lung & bronchus 31% Prostate 10% Colon & rectum 8% Pancreas 6% Liver & intrahepatic bile duct 4% Leukemia 4% Esophagus 4% Urinary bladder 3% Non Hodgkin lymphoma 3% Kidney & renal pelvis 3% All other sites 24% 26% Lung & bronchus 15% Breast 9% Colon & rectum 6% Pancreas 6% Ovary 3% Non Hodgkin lymphoma 3% Leukemia 3% Uterine corpus 2% Liver & intrahepatic bile duct 2% Brain/ONS 25% All other sites Figure 8. The United States Cancer Statistics from 1999 to 2005 [8].

17 Figure 8. The United States Cancer Statistics from 1999 to 2005 [8].

18 References: [1] Yeh JI et al, Biosens. Bioelectron. 2005, 21, [2] Yeh JI, Nanomaterials for Biosensors. 2006, [3] Yeh JI et al, Biosen. Bioelectron. 2007, 23, [4] Shi HB et al, Nanomedicine. 2007, 2: [5] Shi HB et al, Nanomedicine. 2007, 2, [6] Yeh JI et al; manuscript in preparation. [7] Achim C et al, U.S. Published Patent Application, 2009/ [8] [9] Fernández Sánchez C, J Immunol Meth. 2005,307,1 12. [10] Yeh JI et al; manuscript in preparation.