Development of a biosensor for detection of pleural mesothelioma cancer biomarker using surface imprinting

Our plain-English summary of Development of a biosensor for detection of pleural mesothelioma cancer biomarker using surface imprinting, by A. Mathur, S. Blais, C.M. Goparaju, et al (PloS One, 2013).

The study

• Authors: A. Mathur, S. Blais, C.M. Goparaju, T. Neubert, H. Pass, K. Levon
• Journal: PloS One
• Published: 2013;8(3):e57681
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Hyaluronan-linked protein 1 (HAPLN1) which has been shown to be highly expressed in malignant pleural mesotheliomas (MPM), was detected in serum using an electrochemical surface-imprinting method. First, the detection method was optimized using Bovine serum albumin (BSA) as a model protein to mimic the optimal conditions required to imprint the similar molecular weight protein HAPLN1. BSA was imprinted on the gold electrode with hydroxyl terminated alkane thiols, which formed a self-assembled monolayer (SAM) around BSA. The analyte (BSA) was then washed away and its imprint (empty cavity with shape-memory) was used for detection of BSA in a solution, using electrochemical open-circuit potential method, namely potentiometry. Factors considered to optimize the conditions include incubation time, protein concentration, limit of detection and size of electrode. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to confirm selectivity of imprints. With the obtained imprinting control parameters, HAPLN1 was imprinted in duplicate and the detection of spiked HAPLN1 was successfully conducted in serum.

In plain English

This was a laboratory study that built and tested a sensor meant to detect HAPLN1. The authors described HAPLN1 as overexpressed in most mesotheliomas and a candidate marker for malignant pleural mesothelioma. No patients or asbestos-exposed people were studied. The sensor used a gold electrode with a thin coating containing protein-shaped cavities and measured changes in electrical potential when protein bound. The authors first tuned the method with bovine serum albumin, a protein of similar size. Of the coating times tested, 12 hours produced the most stable imprints. Small electrodes gave responses of 15–20 mV, compared with 2–4 mV for control electrodes carrying only the coating. Mass spectrometry showed myoglobin bound to its own cavities but not to albumin cavities. HAPLN1-imprinted electrodes gave a 25 mV response to HAPLN1 in buffer, with a low response to albumin. In serum with HAPLN1 added, the electrode drifted strongly, but the authors reported a marked change in potential. The authors concluded the sensor detected picomolar concentrations within 2–5 minutes. They noted that the signal's mechanism is not clearly understood and that clinical validation is planned.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory development study of an electrochemical (potentiometric) biosensor using surface molecular imprinting
• Who was studied: No human subjects. The experiments used bovine serum albumin as a model protein, myoglobin, and purchased recombinant human HAPLN1 protein. Three HAPLN1-imprinted gold electrodes were made. Human serum was spiked with HAPLN1.
• Exposure: Not applicable: no asbestos exposure was studied; the work tested detection of the protein HAPLN1 in buffer and in spiked serum
• Main results:
  • Of the incubation times tested (2, 6 and 12 hours), the authors reported that 12 hours formed more stable imprints
  • With bovine serum albumin, a potential increasing with concentration was seen only for the electrode incubated for 12 hours
  • Small albumin-imprinted gold electrodes gave a binding response of 15–20 mV, versus 2–4 mV for control electrodes with only the coating layer
  • By mass spectrometry (MALDI-TOF), myoglobin bound to myoglobin-imprinted cavities but not to albumin-imprinted cavities
  • HAPLN1-imprinted electrodes gave a 25 mV response to HAPLN1 in buffer, compared with a low response to albumin
  • In serum spiked with HAPLN1, the imprinted electrode showed high drift
  • The authors reported a marked potential change to HAPLN1 in spiked serum, with results similar to those in buffer
• The authors' conclusion: The authors concluded that the sensor showed a limit of detection in the picomolar range with a response time of 2–5 minutes
• Limitations the authors state:
  • Specificity for albumin could not be confirmed by MALDI-TOF because the equipment was poorly sensitive to large proteins
  • How protein binding produces the electrical signal is not clearly understood
  • Further specificity testing and clinical data for validation were planned for future work

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker.

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