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Biopsies are a widely used diagnostic tool utilized in various clinical applications. Despite its usefulness, this technique must often be performed in conjunction with imaging techniques that are not sensitive to the differences that exist between cancerous and normal tissues.
In an effort to improve the sensing capabilities of traditional biopsy needles, a novel biopsy needle integrated with multiplexed physical/chemical sensing has shown promising results in early pre-clinical studies.
An Overview of Biopsies
When a suspicious lesion is found on or within a patient, histological assessment of the tissue within that lesion is crucial. To achieve this tissue sample, a biopsy is performed, a medical procedure that extracts the tissue sample from the patient’s body.
During a biopsy, a needle is accurately positioned directly towards the lesion to allow the sample to be collected right in front of the needle's tip.
This precise direction of the biopsy needle can be achieved through various medical imaging tools, including ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI). These imaging tools are often limited in their ability to discern healthy tissue from potentially diseased tissue.
As a result, clinicians must often take several biopsy samples, which, for prostate biopsies, can involve up to 12 different points of the prostate that are extracted for histological assessment.
Growing Interest in Multimodal Devices
The modern medical field incorporates a wide range of optical and electrochemical sensing techniques, some of which include colorimetric analyses, chemiluminescence-, fluorescence-, surface plasmon resonance (SPR)-, potentiometry-and amperometry-based modalities.
Applicable for both biosensing and quantification purposes, these techniques assist clinicians during clinical diagnoses, DNA sequencing, immunoassays, metabolite quantification and protein detection.
More often than not, the biomarkers used for these assays can be detected by the use of multiple single-mode laboratory instruments. A colorimetric assay, for example, will be read by a spectrophotometer that is comprised of both a photosensitive light detector and an illumination source.
Recent efforts to improve electrochemical sensing devices, such as those used to detect metabolites, have found that multiple sensors and electronic circuits can be integrated onto a single chip. A single sample can be used to analyze multiple biomarkers, reducing costs and improving patient care.
Can Sensors Be Used in Biopsy Needles?
The recent advancements in multimodal sensors for clinical diagnoses, combined with the need to improve the accuracy of current biopsy methods have led researchers to investigate the potential of a biopsy needle that has been integrated with a multi-modal sensor.
This effort has been further supported by several findings that have demonstrated a significant difference to exist in the electrical conductivity of normal tissues as compared to cancerous tissues, particularly in cases dealing with breast, liver, lung, prostate and skin cancers.
Several studies have found that normal and cancerous tissues exhibit significant differences in both pH and glucose concentrations, which is largely attributed to the intrinsic metabolic processes of cancer cells; therefore, having the potential to also be a source of tissue differentiation during biopsies.
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While several attempts have been made to integrate electrical sensors into the biopsy needle, the extremely small diameter of the needle, which is typically less than 1.2 millimeters (mm), has been a limiting factor.
One of the earliest attempts to create a biopsy needle equipped with sensing capabilities occurred in 2013 when a group of Dartmouth researchers designed an electrical impedance spectroscopy (EIS) sensing biopsy needle.
Although their novel device was found to discriminate cancer from benign tissues, the researchers were only able to use a 2-electrode sensor configuration in their needle design, which limited the sensor types.
A Novel Multiplexed Sensing Biopsy Needle
The rapid growth in sensor technology over the past several years has inspired a joint research initiative between scientists from the Korea Advanced Institute of Science and Technology (KAIST) and the University of California at San Diego to design a biopsy needle integrated with multi-modal physical/chemical sensor array.
To integrate the biosensor electrodes into the biopsy needle, the electrodes were initially fabricated onto a polyimide (PI) substrate through photolithography, electron beam evaporation and lift-off process.
Each of the biosensors, which are capable of detecting differences in pH, glucose and electrical conductivity, had a thickness of less than 20 micrometers (µm).
Once each of the biosensors was successfully fabricated onto the substrate, the multi-modal physical/chemical sensor array was then integrated onto the surface of a stainless steel biopsy needle. Notably, since the biosensors were coated with a pressure-sensitive adhesive (PSA), the researchers were able to easily attach the array directly onto the surface of the biopsy needle. The biopsy needle was then inserted into a polyethylene terephthalate (PET) heat-shrink tube to complete thermal treatment.
To test the efficacy of this multi-modal physical/chemical sensing device, several preliminary studies on three different solutions, including sodium chloride (NaCl), potassium phosphate buffer (PBS) and glucose.
Before testing an actual biological sample, the researchers then evaluated the efficacy of their device using an agarose hydrogel complex comprised of both normal and cancerous liver tissue-mimicking hydrogels. Finally, their biological sample was a porcine liver that had been exchanged with different physical and chemical parameters.
In all sample types, the researchers found that their multi-modal sensor successfully provided accurate information on the physical, chemical and biochemical characteristics, demonstrating its potential to transform current biopsy procedures.
References and Further Reading
Park, J., Jeong, Y., Kim, J., Gu, J., Wang, J., et al. (2020). Biopsy needle integrated with multi-modal physical/chemical sensor array. Biosensors and Bioelectronics 148. doi:10.1016/j.bios.2019.111822.
Al-Rawhani, M. A., Hu, C., Giagkoulovits, C., Annese, V. F., et al. (2019). Multimodal Integrated Sensor Platform for Rapid Biomarker Detection. IEEE; 614-623. doi:10.1109/TBME.2019.2919192.
Mishra, V., Schned, A. R., Hartov, A., Heaney, J. A., et al. (2013). Electrical property sensing biopsy needle for prostate cancer detection. Prostate 73(15); 1603-1613. doi:10.1002/pros.22695.
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