Quantification Of C-reactive Protein Research Articles

A Visual Distance-Based Capillary Immunoassay Using Biomimetic Polymer Nanoparticles for Highly Sensitive and Specific C-Reactive Protein Quantification.

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.

Development of a C-reactive protein quantification method based on flow rate measurement of an ink solution pushed out by oxygen gas generated by catalase reaction.

A novel determinationmethod for protein biomarkers based on on-chip flow rate measurement was developed using a microchip with organic photodiodes (OPDs). This quantitative method is based on the flow rate measurement of an ink solution pushed out by oxygen gas generated through catalase reaction. The amount of oxygen gas generated in the sample reservoir is dependent on the concentration of the analyte; therefore, the flow rate of the ink solution is also dependent on the concentration of the analyte. The concentration of the analyte can thus be estimated by measurement of the ink solution flow rate. The ink solution flow rate was estimated by measuring the migration time of the ink solution between two points using two OPDs placed below the microchannel. The principle of this method was demonstrated by the measurement of catalase using the microchip. In addition, the developed method was applied to the determination of C-reactive protein (CRP), a biomarker of inflammation, based on a catalase-linked immunosorbent assay (C-LISA). The limit of detection for CRP was 0.20µg/mL. The method was also applied to the determination of CRP in human serum, and the quantitative values obtained by this method were in excellent agreement with those obtained by the conventional enzyme-linked immunosorbent assay (ELISA) method. The developed method does not require a photodetector with high sensitivity and is thus capable of downsizing; therefore, this will be useful for on-site analyses such as point-of-care testing and field measurements.

Ultrafast Biomarker Quantification through Reagentless Capacitive Kinetics.

We introduce a facile assessment of binding kinetics at bioreceptive redox-active interfaces as a means of quantifying target proteins. This is achieved by monitoring the redox capacitance (Cr) of a receptor-modified conductive polymer interface under continuous flow. Exemplified with the quantification of C-reactive protein (CRP), capacitance analyses resolve both the association and dissociation regimes in real-time. Significantly, the rate of electrochemical signal change within the association regime is a sensitive function of target concentration, enabling marker assaying down to picomolar levels, comparable to end-point assays, in 15 s. This reagentless proof-of-principle methodology is envisioned to be widely applicable to the facile quantification of a range of other pertinent, clinically relevant targets.

Hue-Recognition Strategy-Based Immunoassay Using Functionalized Dendritic Silica Colloids and Gold Nanoclusters for Point-of-Care Testing of C-Reactive Proteins

Considering that hue-recognition has drawn increasing research interests for visual detection because of its high accuracy and flexible analysis modalities, the exploration of a rational hue-recognition sensing system is highly demanded. Here, we report a hue-recognition-based lateral flow immunoassay (HLFIA) by ratiometric modulation of emission from two nanoprobes, in which red-emitting ruthenium(II)-doped dendritic silica colloids and green-emitting gold nanoclusters function as reporter and reference, respectively. The HLFIA strip can generate a visually discernible green-to-orange-red color gradient alternation, enabling the naked-eye semiquantitative inspection of successive C-reactive protein (CRP) concentration and concentration intervals (0–50, 50–150, and 150–500 ng mL–1) with a visual detection limit of 10 ng mL–1. By integrating with a customized smartphone-based portable imaging device and RGB color space recognition, the precise quantification of CRP can be achieved with a linear range of 0–100 ng mL–1 and a limit of detection of 0.64 ng mL–1. The HLFIA strip is robust and validated for CRP detection in real serum, holding great promise for noninstrumental and deprofessionalized point-of-care immunoassay of biomarkers.

C-Reactive protein and the kynurenic acid to quinolinic acid ratio are independently associated with white matter integrity in major depressive disorder

Kynurenic acid (KynA) and quinolinic acid (QA) are neuroactive kynurenine pathway (KP) metabolites that have neuroprotective and neurotoxic properties, respectively. At least partly as a result of immune activation, the ratio of KynA to QA in the blood is reduced in major depressive disorder (MDD) and has been reported to be positively correlated with gray matter volume in depression. This study examined whether the inflammatory mediator, C-reactive protein (CRP) and the putative neuroprotective index, KynA/QA, were associated with white matter integrity in MDD, and secondly, whether any such associations were independent of each other or whether the effect of CRP was mediated by KynA/QA. One hundred and sixty-six participants in the Tulsa 1000 study with a DSM-V diagnosis of MDD completed diffusion tensor imaging and provided a serum sample for the quantification of CRP, KynA, and QA. Correlational tractography was performed using DSI Studio to map the specific white matter pathways that correlated with CRP and KynA/QA. CRP was negatively related to KynA/QA (standardized beta coefficient, SBC = -0.35 with standard error, Std.E = 0.13, p < 0.01) after controlling for nine possible confounders, i.e., age, sex, body mass index (BMI), medication status, lifetime alcohol use, severity of depression, severity of anxiety, length of illness, and smoking status. Higher concentrations of CRP were associated with decreased white matter integrity (fractional anisotropy, FA) of the bilateral cingulum and fornix after controlling for the nine potential confounders (SBC = -0.43, Std.E = 0.13, p = 0.002). Greater serum KynA/QA was associated with increased white matter integrity of the bilateral fornix, bilateral superior thalamic radiations, corpus callosum, and bilateral cingulum bundles after controlling for the same possible confounders (SBC = 0.26, Std.E = 0.09, p = 0.005). The relationship between CRP and FA was not mediated by KynA/QA. Exploratory analyses also showed that KynA/QA but not CRP was associated with self-reported positive affect, attentiveness, and fatigue measured with the PANASX (SBCs = 0.17–0.23). Taken together, these results are consistent with the hypothesis that within a subgroup of MDD patients, a higher level of systemic inflammation alters the balance of KP metabolism but also raise the possibility that CRP and neuroactive KP metabolites represent independent molecular mechanisms underlying white matter alterations in MDD.

One-Shot Full-Range Quantification of Multi-Biomarkers With Different Abundance by a Tandem Giant Magnetoresistance Assay.

In this study, we reported a tandem giant magnetoresistance (GMR) assay that realized the one-shot quantification of multi-biomarkers of infection, C-reactive protein (CRP) with procalcitonin (PCT), and neutrophil gelatinase-associated lipocalin (NGAL), all of which could cover their clinically relevant concentration ranges under a different principle. In the presence of co-determined assay, we quantified these three biomarkers in undiluted human blood serum in a single test. The tandem principle, based on which quantification of CRP occurs, combines a sandwich assay and an indirect competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve (‘Hook’ effect), which characterizes the one-step sandwich assay at high CRP concentrations. However, the entire diagnostically dynamic range, in the quantification of PCT and NGAL, was achieved by differential coating of two identical GMR sensors operated in tandem and by combining two standard curves. The sensor quantified low detection limits and a broader dynamic range for the detection of infection biomarkers. The noticeable features of the assay are its dynamic range and small sample volume requirement (50 μL), and the need for a short measurement time of 15 min. These figures of merit render it a prospective candidate for practical use in point-of-care analysis.

Open Circuit Potential as a Tool for the Assessment of Binding Kinetics and Reagentless Protein Quantitation.

A microfluidic open circuit potential label-free protein assay was developed for the reagentless quantification of C-reactive protein (CRP), a model protein target, and further utilized to assess target-receptor binding kinetics. Generated sensors have very high baseline stabilities (<1% change in 100 min) and high levels of selectivity in complex media. Real-time assays are fast (<20 min), of high sensitivity (1 ng/mL limit of detection for CRP in serum), and resolve kinetic and thermodynamic characteristics that correlate well with those resolved optically. The assay shows excellent correlation with an enzyme-linked immunosorbent assay analysis of patient samples. The methodology has value in potentially underpinning a low-cost, rapid, and sensitive single-step biomarker quantification.

Label-free detection of C-Reactive protein using bioresponsive hydrogel-based surface relief diffraction gratings

Responsive hydrogel-based surface relief gratings have demonstrated great performances as transducers in optical sensing. However, novel and smart designs of hydrogels are needed for the appropriate detection of analytes and biomolecules since the existing materials are very limited to specific molecules. In this work, a biosensing system based on surface relief gratings made of bioresponsive hydrogels has been developed. In particular, the hydrogel contains phosphocholine moieties to specifically recognize C-Reactive protein (CRP). The CRP-Sensing hydrogel capacity to selectively detect CRP was fully demonstrated. Using Direct Laser Interference Patterning, micro-gratings were created on CRP-Sensing hydrogel substrates and applied for the label-free sensing of CRP using a simple laser-based homemade optical setup. Limits of detection (LOD) and quantification (LOQ) in human serum dilutions of 1.07 and 8.92mgL-1, respectively, were reached. These results demonstrate that the biosensing system allows the selective label-free detection of CRP within concentration ranges around those related to risks of cardiovascular diseases and sepsis. Besides, amplification strategies have been carried out improving the sensitivity, widening the linear range, and reaching better LOD and LOQ (0.30mgL-1 and 4.36mgL-1). Finally, all the approaches were tested for the quantification of CRP in certified human serum with recoveries of around 100%.

Dynamic Range Expansion of the C-Reactive Protein Quantification with a Tandem Giant Magnetoresistance Biosensor.

In this study, we report a convenient analytical method for a full-range quantification of the C-reactive protein (CRP), a blood biomarker of infection and cardiovascular events. We determine CRP over the entire diagnostically relevant concentration range in undiluted human blood serum in a single test, using a tandem giant magnetoresistance (GMR) sensor. The tandem principle combines a sandwich assay and a competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose–response curve (“Hook” effect), which characterizes the one-step sandwich assay at high CRP concentrations. The sensor covers a linear detection range for CRP concentration from 3 ng/mL to 350 μg/mL, the detection limit (s/n = 3) is 1 ng/mL. The prominent features of the chip-based method are its expanded dynamic range and low sample volume (50 μL), and the need for a short measurement time of 15 min. These figures of merit, in addition to the low detection limit equal to the established assay instrumentation, make it a viable candidate for use in point-of-care diagnostics.

A sensitive and quantitative prognosis of C-reactive protein at picogram level using mesoporous silica encapsulated core-shell up-conversion nanoparticle based lateral flow strip assay

C- reactive protein (CRP) is a sensitive indicator for infectious or inflammatory diseases in human which can reflect the body's inflammation latency and early pathophysiological changes. The most common detection method of serum CRP is ELISA that has been proved to be expensive and time-consuming, restricting its use in point-of-care application. In this paper, we demonstrated a lateral flow system for CRP quantification by using mesoporous silica (mSiO2) coated up-converting nanoparticles (UCNPs) (denoted as UCNPs@mSiO2) as fluorescent labels. The up-converting core can emit strong green fluorescence signals under NIR excitation light (980 nm) with excellent photostability, high signal-to-noise ratio and low background fluorescence. By wrapping ultrathin mSiO2 outside, the core-shell structured UCNPs@mSiO2 exhibits good dispersity and stability meanwhile maintains strong fluorescence emission. Besides, the mSiO2 shell provides further functionalities for antibody linkage. By using a portable fluorescence sensor, we reached a CRP detection limit of 0.05 ng/mL and a linear range from 0.1 ng/mL-50 ng/mL, and the detection time was no more than 8 min. The lateral flow test strips exhibit great stability in CRP quantification (CV%<5) and have a life time of more than 1 week at ambient temperature. Furthermore, the proposed system can work with a cloud-enabled smartphone through Bluetooth for Internet of Medical Things application. This CRP detection method proves to be rapid and easy-operated, which has great potential in early inflammatory disease perception in the point-of-care tests and future's 5G-enabled remote healthcare management.

Functionalized ultra-fine bimetallic PtRu alloy nanoparticle with high peroxidase-mimicking activity for rapid and sensitive colorimetric quantification of C-reactive protein.

Thein situ synthesis is reportedof citric acid-functionalized ultra-fine bimetallic PtRu alloy nanoparticles (CA@PtRu ANPs) through a simple one-pot wet chemical method. The cost-efficient CA@PtRu ANPs with an average diameter of 3.2nm revealed to have enhanced surface area, peroxidase-like activity, high stability, and adequate availability of functional groups to bind biomolecules. Along with nanoparticle surface area, the surface charge has also significantly affected the peroxidase-like activity and the colloidal suspension stability. As an excellent immobilization matrix and peroxidase mimic, the CA@PtRu ANPs were utilized to develop non-enzymatic colorimetric immunoassay for rapid, selective, and sensitive quantification of C-reactive protein (CRP) biomarkers. In this immunoassay, CA@PtRu ANPs serve as enzyme mimic that significantly amplifies the color signals, and amine-functionalized silica-coated magnetic microbeads (APTES/SiO2@Fe3O4) act as CRP-recognizing capture probes. The absorbance curves of colorimetric immunoassay were measured in wavelengths between 550 and 750nm, and the maximum absorbance at 652nm was used to establish a linear relationship between absorbance and CRP concentrations. The developed colorimetric immunoassay showed rapid and sensitive quantification of CRP levels from 0.01 to 180μgmL-1 with a LOD of 0.01μgmL-1. Moreover, the mean recovery of CRP from spiked human serum samples lies between 97 and 109% (n = 3), which indicates that the proposed nanozyme-linked immunoassay has the potential to be used in rapid point-of-care applications.

Quantification of CRP in human serum using a handheld fluorescence detection system for capillary-based ELISA

We developed a handheld fluorescence detection system for capillary-based enzyme-linked immunosorbent assay (ELISA). The detection system implements both a long-pass filter and perpendicular optical arrangement, i.e., a power LED and a palm-sized spectrometer, to minimize background signals from the excitation light and optical scattering. The lower detection limit for resorufin was 0.13 μM. The detection system was applied to the quantification of C-reactive protein (CRP) in human serum with a capillary-based ELISA. The lower detection limit for CRP was 31 ng/ml, and the observed CRP levels in human serum were comparable to those obtained with a conventional ELISA system.

One-step non-competitive fluorescence polarization immunoassay based on a Fab fragment for C-reactive protein quantification

A non-competitive fluorescence polarization immunoassay (FPIA) using a Fab fragment was developed for large molecule quantification. Most conventional FPIAs are homogeneous and competitive immunoassays. With competitive FPIAs, it has been difficult to obtain sufficient detection sensitivity when targeting large molecules like proteins. To overcome this fundamental drawback, we report a non-competitive FPIA using a fluorescence-labeled Fab fragment. C-reactive protein (CRP) was used as model substance for validation of the Fab-based non-competitive FPIA. Quantitative analysis of CRP in phosphate buffered saline (PBS) was successfully achieved and the limit of detection (LOD) of CRP in PBS was 207 ng/mL. Moreover, using far-red emitting fluorescent dye (HiLyte Fluor™647) as a fluorescent labeling substance of Fab fragment, we measured CRP in human serum without pretreatment of a sample in 10 min around the cut-off value of CRP (10 μg/mL). The LOD of CRP in human serum was 1.58 μg/mL. In our proposed method, the reaction was completed in a simple one-step mixing with only one type of fluorescence-labeled Fab fragment reagent, and no washing operation was required. Therefore, rapid protein quantification was achieved with a greatly simplified procedure.

Reusable Immunosensor for Detection of C‐reactive Protein in Human Serum

AbstractThis work describes the preparation of a reusable electrochemical immunosensor for detection of C‐reactive protein (CRP), based in modified carbon electrode with reduced graphene oxide and polytyramine as strategy for anchoring the anti‐CRP probe. This immunosensor was able to distinguish different concentrations of CRP target in human serum, by differential pulse voltammetry, showing a linear response from 1.09 to 100 μg L−1. The performance of the immunosensor allowed its application in four consecutive assays, without activity loss. Analyses by atomic force microscopy, scanning electron microscopy and electrochemical impedance spectroscopy corroborate with voltammetric analysis. The immunosensor showed selectivity, stability and reusability, being a promising platform for point‐of‐care quantification of CRP.

Monitoring the level of infection by COVID-19: an previous experiment to possibility of future application to the C-reactive protein detection by bioelectric signals

C-reactive protein (CRP) is a marker of inflammation and infection, and is altered in COVID-19 patients. 2-methacryloyloxyetyl phosphorylcholine (MPC) is a polymer containing phosphorylcholine, a protein that anchors CRP. The purpose of this work was to detect CRP by bioelectric signal resulting from its interaction with MPC. The signal acquisition system was elaborated using Arduino in conjunction with the Parallax Data Acquisition (PLX-DAQ) program for data transfer to Excel, which allowed the treatment of the obtained signal. 10 volunteers were also enrolled to provide blood samples for the purpose of using CRP on confectioned biomaterial containing MPC. After pipetting the volunteer's blood serum into the biomaterial containing MPC, it was possible to obtain a bioelectric signals from the interaction of MPC with CRP. It is concluded that it is possible to detect the presence of CRP by bioelectric signal, and that the use of MPC is promising for future application in collection strips, which would allow the quantification of CRP by portable electronic equipment. An application example would be monitoring the infection level of patients with COVID-19.

C-reactive protein and ART outcomes: a systematic review.

A dynamic balance between pro- and anti-inflammatory factors contributes to regulating human female reproduction. Chronic low-grade inflammation has been detected in several female reproductive conditions, from anovulation to embryo implantation failure. C-reactive protein (CRP) is a reliable marker of inflammation that is extensively used in clinical practice. Recent studies quantified CRP in the serum of infertile women undergoing ART and suggested its potential for the prediction of ART reproductive outcomes. The first objective of this systematic review of the available literature was to evaluate the association between pre-implantation circulating CRP concentration and pregnancy rates in women undergoing ART. The second objective was to describe serum CRP concentration changes after early embryo implantation. The changes in circulating CRP throughout the ART cycle, clinical implications of CRP quantification for the management of women undergoing ART, and future therapeutic options will also be discussed. The MEDLINE database was systematically searched from inception to March 2019 using the following key words: (C-reactive protein) AND (assisted reproductive techniques OR ovulation induction OR insemination OR in vitro fertilization). Only articles in English were considered. Studies were selected based on title and abstract. The full text of potentially relevant articles was retrieved and assessed for inclusion by two reviewers (S.B. and S.H.). The protocol was registered in the International prospective register of systematic reviews (PROSPERO; registration number: CRD148687). In total, 10 studies were included in this systematic review. Most of these studies reported lower circulating CRP values before the window of implantation and higher circulating CRP values during the peri-implantation period in women with successful ART outcome (biochemical or clinical pregnancy) compared to women without a successful outcome. Several lifestyle factors and/or drugs that reduce the concentration of circulating CRP significantly improve ART outcomes. Subgroup analyses according to female BMI and baseline circulating CRP concentration are highly recommended in future analyses. These findings highlight a possible detrimental impact of preconception high circulating CRP concentration on ART outcomes. However, the biochemical or clinical pregnancy rate endpoints used in the studies examined here are insufficient (there were no data on live birth outcome), and the impact of major variables that can influence CRP and/or ART, for example maternal age, BMI, number of transferred embryos, and use of anti-inflammatory drugs, were not considered in the analyses. CRP quantification may be a potential marker of ART outcome, but its predictive value still needs to be investigated in large prospective studies. In future, the quantification of circulating CRP before starting ART could help to identify patients with a poor ART prognosis, leading to ART cycle cancellation or to preconception treatment to minimize the medical risks and costs.

Amperometric immunosensor based on covalent organic frameworks and Pt/Ru/C nanoparticles for the quantification of C-reactive protein.

Anultrasensitive and nonenzymatic electrochemical sandwich-type immunoassay using covalent organic framework (COF-LZU1) material applied as a fixed matrix was developed for the determination of C-reactive protein (CRP). COFs with large specific surface area, good conductivity and stability were employed for functionalisation of the surface. Au nanoparticles were loaded on COF-LZUl to immobilise the CRP antibody (anti-CRP) on the surface of a glassy carbon electrode. Microwave method was employed for the synthesis of the Pt/Ru/C nanoparticles to imitate the protein enzyme with high catalytic activity. The as-synthesised activated carbon-supported bimetallic Pt/Ru/C nanoparticle composite was used to label secondary CRP antibody because it exhibited excellent catalytic behaviour toward hydrogen peroxide. After incubation of CRP, Pt/Ru/C-labelled anti-CRP was combined with CRP through specific antibody-antigen recognition process. The reduction current of H202 at - 0.2V catalysing by tag Pt/Ru/C as measured by a chronoamperometric method is proportional to the concentration of CRP. Under optimal experimental conditions, employing chronoamperometry to investigate the CRP, the obtained linear range was 0.2 to 20ng/mL with adetection limit of 0.1ng/mL. This immunosensor provides an attractive platform for the applicability of COF-LZU1 materials and Pt/Ru/C nanoparticles in electrochemical assays. Graphical abstract An ultrasensitive and nonenzymatic electrochemical immunoassay using covalent organic frameworks (COF-LZU1) material as the fixed matrix was developed for the detection of C-reactive protein (CRP). Microwave method was employed to synthesis the bimetallic metal composites Pt/Ru/C nanoparticles, which exhibited excellent catalytic behavior toward small molecules H2O2. COFs with large specific surface area, good conductivity and stability were employed for surface functionalization. Our proposed biosensor is highly sensitive, with the detection limit of 0.1 ng/mL.

Ultrasensitive Impedimetric Immunosensor for the Detection of C-Reactive Protein in Blood at Surface-Initiated-Reversible Addition-Fragmentation Chain Transfer Generated Poly(2-hydroxyethyl methacrylate) Brushes.

The reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-hydroxethyl methacrylate (HEMA) from a surface confined, dithio-tethered, chain transfer agent (CTA) enables the preparation of electrode-tethered poly(2-hydroxyethyl methacrylate) (pHEMA) brushes of well-defined thickness with convenience and exceptionally high interfacial impedimetric baseline stability. The subsequent covalent integration of antibodies generates interfaces of very high target recognition specificity, ultimately enabling femtomolar levels of quantification of C-reactive protein (CRP) and recovery in spiked serum samples of ∼98%. When combined with the intrinsic scalability of the reagentless electrochemical impedance spectroscopy (EIS) platform, and the innate high levels of polymer tuneability and control, we believe this represents a valuable contribution to the diagnostic toolbox.

Quantification of C-reactive protein, differential count and blood glucose in acute coronary syndrome

Background: The study was done to investigate whether the raised levels of C-reactive protein (CRP), differential count and random blood glucose, besides echocardiogram, enhances the assessment process of acute coronary syndrome (ACS).Methods: This prospective study was done on 100 patients with typical chest pain attending to the department of medicine at K.A.P.V Medical College and Hospital, Trichy during the period from 2015 to 2017. The serum was assayed on admission for CRP, differential count and random blood glucose. Correlation of these parameters with incidence of ACS was calculated.Results: Male preponderance was seen in the study. Out of 100 patients, majority of about 60% of ACS patients had raised JVP. Elevated level of CRP was seen in 73% patients, 70% had elevated level of ejection fraction percentage. 71% had elevated level of WBC and 58% had elevated level of RBS. Statistically significant correlation was observed with the level of CRP (p=0.044), differential WBC count (p=0.037) and random blood glucose levels (p=0.001).Conclusions: Our study indicates that elevated CRP levels, increased random blood sugars and leucocytosis in ACS patient are positively correlated with decreased ejection fraction. Hence, measuring the levels of these parameters will helps in identifying incidence of acute coronary syndrome without echocardiogram.

Femtosecond-Pulsed Laser Written and Etched Fiber Bragg Gratings for Fiber-Optical Biosensing.

We present the development of a label-free, highly sensitive fiber-optical biosensor for online detection and quantification of biomolecules. Here, the advantages of etched fiber Bragg gratings (eFBG) were used, since they induce a narrowband Bragg wavelength peak in the reflection operation mode. The gratings were fabricated point-by-point via a nonlinear absorption process of a highly focused femtosecond-pulsed laser, without the need of prior coating removal or specific fiber doping. The sensitivity of the Bragg wavelength peak to the surrounding refractive index (SRI), as needed for biochemical sensing, was realized by fiber cladding removal using hydrofluoric acid etching. For evaluation of biosensing capabilities, eFBG fibers were biofunctionalized with a single-stranded DNA aptamer specific for binding the C-reactive protein (CRP). Thus, the CRP-sensitive eFBG fiber-optical biosensor showed a very low limit of detection of 0.82 pg/L, with a dynamic range of CRP detection from approximately 0.8 pg/L to 1.2 µg/L. The biosensor showed a high specificity to CRP even in the presence of interfering substances. These results suggest that the proposed biosensor is capable for quantification of CRP from trace amounts of clinical samples. In addition, the adaption of this eFBG fiber-optical biosensor for detection of other relevant analytes can be easily realized.