Preparation Of Disposable Microneedle Patch Sensor And Its Application In Analysis And Detection

Cutaneous Interstitial Fluids（ISF）are novel sources of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment.Extraction and analysis of ISF are challenging.Microneedle technology is an emerging technology in recent years,which plays an important role in sampling,sensing and transdermal drug delivery.Microneedles can extract ISF in a minimally invasive manner and can be integrated with Point-of-Care Testing（POCT）systems to detect biomarkers,providing real-time diagnosis.At present,most of the microneedle sensors are based on electrochemical analysis method.The microneedle is used as an electrode and connected with electrochemical equipment to analyze various targets.However,this method often requires complex equipment and extra battery,which is expensive and not environmental-friendly when exposed.To solve the above problems,we combined the microneedle technology with colorimetric method to prepare disposable microneedle colorimetric patch for the detection of health-related analytes in ISF,and used it in conjunction with smart phones for quantitative analysis of the targets.The developed devices is with simple operation,cost effective,and without the requirement of complex equipment and professional operators.The main research results are as follows:（1）We proposed a wearable transdermal microneedle colorimetric patch based on photonic crystal hydrogel for glucose detection.The microneedle device was equipped with a photonic crystal hydrogel film to measure glucose concentration.After the stainless steel microneedle penetrated the skin,interstitial fluids were driven by capillary force into the microfluidic channel above the microneedle device and contacted with the hydrogel film.The functionalized hydrogel film modified by3-amino-phenylboronic acid can respond to glucose in cutaneous interstitial fluids,and its volume changed with the change of glucose concentration,the nano-structure of photonic crystal changed,and the reflected wavelength changed accordingly.Therefore,glucose concentration in cutaneous interstitial fluids can be quantitatively detected.To make the detection more convenient and accurate,we combined the determination process with smart phones.The glucose concentration in the actual sample can be accurately obtained by taking a picture of the sample with a smartphone and further analyzing the image with a MATLAB program built into the phone.The experimental results on pig skin in vitro were in good agreement with those determined by glucose meter.The feasibility of application of this device in complex biological samples was demonstrated.（2）We developed a wearable double microneedle colorimetric patch based on peroxisase-like polypyrrole nanoparticles（PPy NPs）for the on-site detection of uric acid.Uric acid oxidase were embedded in polyvinyl alcohol microneedles to catalyze the oxidation of uric acid extracted from interstitial fluids and produced H₂O₂.PPy NPs and 3,3’,5,5’-tetramethylbenzidine（TMB）were encapsulated in the display layer,and PPy NPs triggerd a reaction between H₂O₂ and TMB,resulting in the color change in the display layer associated with H₂O₂ concentration.Therefore,uric acid levels can be determined visually.With the help of a smart phone,the image was analyzed by MATLAB program built in the phone,and the uric acid concentration was directly read through the relationship between uric acid concentration and color intensity.Moreover,the designed microneedle patch sensor exhibited good selectivity and stability.The experiment on pig skin in vitro also shows the practical application of microneedle colorimetric patch.（3）By building a microfluidic device,photonic crystal spheres with various reflection wavelengths were prepared.Photonic crystal hydrogel spheres was modified by Phenylboronic Acid for glucose detection.The color of photonic crystal spheres varies with glucose concentration.The photonic crystal hydrogel spheres have the advantages of small size and no color change with viewing angle,etc.They can be combined with microneedle to construct microneedle colorimetric sensor to detect a variety of interesting analytes.