Needle-Shaped Biosensors for Precision Diagnoses: From Benchtop Development to In Vitro and In Vivo Applications

Abstract

To achieve the accurate recognition of biomarkers or pathological characteristics within tissues or cells, in situ detection using biosensor technology offers crucial insights into the nature, stage, and progression of diseases, paving the way for enhanced precision in diagnostic approaches and treatment strategies. The implementation of needle-shaped biosensors (N-biosensors) presents a highly promising method for conducting in situ measurements of clinical biomarkers in various organs, such as in the brain or spinal cord. Previous studies have highlighted the excellent performance of different N-biosensor designs in detecting biomarkers from clinical samples in vitro. Recent preclinical in vivo studies have also shown significant progress in the clinical translation of N-biosensor technology for in situ biomarker detection, enabling highly accurate diagnoses for cancer, diabetes, and infectious diseases. This article begins with an overview of current state-of-the-art benchtop N-biosensor designs, discusses their preclinical applications for sensitive diagnoses, and concludes by exploring the challenges and potential avenues for next-generation N-biosensor technology.

Keywords: clinical biomarkers; complex clinical samples; in situ detection; needle-shaped biosensor; precision diagnosis.

Figure 1

Timeline highlighting significant milestones in the development and application of needle-shaped biosensors (N-biosensors) over the past few decades. These landmark biosensors include optical fibre sensor for measuring blood PH [14], needle electrode sensor for monitoring glucose [15], SPR sensor for detecting IgG and anti-IgG [16], fluorescent sensor for measuring Calcium ions [17], SPR sensor for identifying blood type [5], sensor for continuously monitoring lactate [18], microneedle array for analysing glucose [19], sensor for detecting Nitric Oxide [20], microneedle sensor for tracking glucose dynamics [21], sensor for detecting IL-1β [8,9] and Penicillin V [22], sensors for continuously monitoring Lactate [23] and levodopa [24], MIP sensor for cardiac troponin 1 [25] and spike protein [26], and sensor for real-time monitoring Tobramycin [27] and Etoposide [28].

Figure 2

Examples of clinically used N-biosensor designs detailing their physical structures, recognition modules, and targeted organs or tissues. Commonly employed N-biosensor structures include microneedles (A1), acupuncture needles (A2), stainless steel needles (A3–A5), and nanoneedles (A6). The choice of N-biosensor shape also depends on the targeted organ or tissue. The primary recognition modules utilised are antibodies (B1), aptamers (B2), oxidases (B3), and MIPs (B4).