Review
TRENDS in Biotechnology
Vol.25 No.3
Biosensor developments: application to prostate-specific antigen detection Declan A. Healy1, Conor J. Hayes1, Paul Leonard1, Louise McKenna2 and Richard O’Kennedy1 1
School of Biotechnology and Biomedical Diagnostics Institute, National Centre for Sensor Research, Dublin City University, Dublin 9, Ireland 2 Forensic Science Laboratory, Garda Headquarters, Phoenix Park, Dublin 8, Ireland
Prostate-specific antigen (PSA) is the best serum marker currently available for the detection of prostate cancer and is the forensic marker of choice for determining the presence of azoospermic semen in some sexual assault cases. Most current assays for PSA detection are processed on large analyzers at dedicated testing sites, which require that samples be sent away for testing. This leads to delays in patient management and increased administration costs. The recent emphasis placed on the need for point-of-care patient management has led to the development of novel biosensor detection strategies that are suitable for the miniaturization of assays for various targets including PSA. This review highlights the current and novel analytical technologies used for PSA detection, which will benefit clinicians, patients and forensic workers in the future. Introduction Prostate cancer (PCa) accounts for 10% of all deaths from cancer [1–4], and the indicator most widely used to detect it is serum prostate-specific antigen (PSA) levels: PSA is a serine protease that is produced by the prostate epithelium to maintain liquefaction of seminal fluid [5]. The importance of PSA as an oncological marker is partly because of the lack of real alternative markers of PCa. Most PSA testing takes place at dedicated centralized laboratories using large, automated analyzers, requiring sample transportation, increased waiting times and increased administration and medical costs. The availability of near-patient or point-of-care testing (POCT) could help to reduce the number of clinic visits, decrease costs to the patient and the healthcare system, increase patient satisfaction and improve clinical outcome. Recent advances in biosensor development, using nanoparticles and nanostructures as integral components, have brought POCT for PSA closer to reality. This review highlights some important biosensor formats that have recently been applied to PSA detection and emphasizes the advantages or disadvantages of each biosensor type with respect to its suitability for use in the POCT devices of the future.
Corresponding author: O’Kennedy, R. (
[email protected]). Available online 24 January 2007. www.sciencedirect.com
Prostate cancer detection using serum PSA measurement Trace levels of PSA are naturally found in the serum; however, PCa tumor growth usually leads to the release of high concentrations of PSA into the circulatory system [6]. A PSA measurement above a cut-off value of 4.0 ng/ml (and more recently 2.5 ng/ml) is generally regarded as positive and might indicate the need for a biopsy. PSA testing is also used to monitor the response of PCa patients to ablative therapy such as radical prostatectomy. In this situation PSA should be undetectable, and a subsequent detectable level of PSA is a sign of disease recurrence. For this reason, ultrasensitive assays that are capable of detecting concentrations of serum PSA in the low pg/ml region have been sought to facilitate earlier detection of recurrence. Despite its wide use, PSA is not a cancer-specific marker, and other non-cancerous diseases of the prostate, such as benign prostatic hyperplasia (BPH), can also lead to increased release of PSA into the circulation. The development of assays that are capable of distinguishing between different isoforms of PSA [1,7], such as the ratio of free PSA to complexed PSA, has helped to improve the distinction between PCa and BPH, particularly in the socalled ‘diagnostic grey zone’ of 4–10 ng/ml PSA [6–10]. PSA detection in forensic samples In addition to its use in the diagnosis of PCa, the detection of PSA has also become the method of choice for the forensic determination of the presence of semen, in the absence of sperm, in sexual assault cases. However, the detection of PSA in forensic samples necessitates different assay requirements than its detection in clinical samples. First, it is not the determination of absolute PSA levels that is important in forensic science, rather the ability to detect PSA in what are invariably ‘dirty’ samples: contamination with other body fluids or dirt, scarcity of the sample, the need for extraction from different types of fabric – leading to low extraction efficiencies – and the decomposition of samples in cadavers or following laundering of fabrics are all common challenges to PSA detection in forensic samples [11]. Second, owing to low concentrations of PSA being naturally present in the tissues and body fluids of some females, PSA assays for forensic use require only limited sensitivity to avoid the danger of false-positive results.
0167-7799/$ – see front matter ß 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tibtech.2007.01.004
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Review
TRENDS in Biotechnology Vol.25 No.3
Table 1. Examples of some commercially available tests commonly used for PSA determinations in serum Manufacturer
Assay
PSA isoform detected
Abbott Diagnostics
Architect
Free PSA Total PSA Free PSA Total PSA Total PSA Total PSA Free PSA Third-generation PSA b Total PSA Free PSA Total PSA Free PSA PSA-ACT
AxSYM
Diagnostic Products Corporation
IMx Immulite
Roche
Elecsys
Beckman Coulter
Access-Hybritech
Bayer Diagnostics
ADVIA
Lowest detection limit (ng/ml)
