A digital Polymerase Chain Reaction (PCR) system sample segmentation chip was developed for the “division” method for samples of a digital PCR system, and a capillary microarray was used for trace biological sample detection. First, arrayed silicon substrates were fabricated using Micro-electron-mechanical Systems(MEMS) technology, subsequently silicon wafers were thinned by the process of high-efficiency, low-damage, and ultra-precision grinding and then combined through chemical modification methods. A capillary microarray with a hydrophobic surface and hydrophilic inner wall was successfully prepared. The structure of the capillary microarray was characterized by scanning electron microscopy (SEM). SEM results showed that the structure of the capillary microarray is a through-hole microarray. The hydrophobicity of the surface of the capillary microarray was characterized by the contact angle, and the contact angles of the surface before and after chemical treatment were compared. The results show that the surface of the capillary microarray is hydrophobic after chemical treatment, and the contact angle is 118°. The hydrophilicity of the inner walls of the capillary microarray was characterized by an energy dispersive spectrometer (EDS). The results show that only Si and O elements are present in the inner walls of the capillary microarray, forming a hydrophilic group (—Si—OH). Thus, the inner walls of the capillary microarray were hydrophilic. The sample segmentation performance of the capillary microarray was characterized by measurement microscopy and fluorescence microscopy. The results show that the capillary microarray divided the sample into uniform independent units. Characterized by the laser confocal scanner, the overall sample segmentation effect of the capillary microarray is intuitively reflected, and the sample addition rate of the chip is 93.8% by counting and calculation. Finally, a capillary microarray chip with a hydrophobic surface and hydrophilic inner wall was successfully prepared and exhibited excellent sample segmentation performance, which offers broad application prospects for the field of biomedics.

To realize rapid quantitative detection of bacteria found in drinking water, a high-throughput quantitative detection system based on flow cytometry was established. The systems signal acquisition system, absolute counting method, and comprehensive performance for bacterial detection were investigated and evaluated. Firstly, according to the fluorescent dyes of typical bacteria found in drinking water and their fluorescence excitation spectra, the working principle and hardware platform of the flow cytometer for rapid bacterial detection were established. Secondly, the signal-to-noise ratio of the signal acquisition system was evaluated by simplifying the calculation model for signal strength of bacterial fluorescence. Next, a calculation method based on the flow sensor method was established for absolute counting. Finally, a series of statistically analyzed control experiments were performed with the self-developed instrument alongside BD LSR Fortessa with absolute reference according to the reference microsphere method. The performance of the self-developed instrument for the detection of bacteria in drinking water was comprehensively tested and evaluated. The experimental results indicated the followings: for a 4 MHz wideband fluorescent signal, the signal-to-noise ratio of the signal acquisition system can reach 86 dB; for microspheres in a certain concentration range, the cv value of the system test results is less than 2%, the correlation coefficient with the test results of the BD instrument is as high as 0.999 6, the linearity of the equivalent dilution microsphere test is up to 0.999 8, and the lowest detectable bacterial concentration is 102 particles/mL; for E.coli and S.aureus bacteria, the cv value of the test results of the system is less than 7%, the correlation coefficient with the test results of the BD instrument exceeds 0.995 9, and the relative deviation is within 4%. The instrument is capable of rapid quantitative detection of bacteria with a high-precision, providing a reference for the development of rapid detection instruments for typical bacteria found in drinking water.

A needle-ring ion source structure based on printed circuit board technology was designed to integrate an ion source with a High-field Asymmetric Ion Mobility Spectrometry (FAIMS) structure, which was composed of a needle electrode, loop electrode, air inflow pedestal, and fixed needle pedestal. A stainless steel needle tip with a diameter of 28 μm was used as the cathode, and a copper loop with a diameter of 3 mm and length of 16 mm was used as the anode. A discharge property experiment shows that corona and glow discharges are realized through discharge voltages of -2 kV and -2.8 kV, respectively, proving that the stable discharge state could be obtained in ambient air. Comparing the FAIMS system using a UV-lamp ion source with the FAIMS system using a needle-ring ion source, the compensation voltages in the FAIMS spectrum are nearly the same under the conditions of a carrier gas flow rate of 1.5 L/min and a high-field rectangular radio peak-to-peak voltage of 300 V. However, the electric currents are 64 pA and 45 pA for the needle-ring and UV-lamp ion sources, respectively. Experimental results thus reveal that the integrated FAIMS using the needle-ring ion source can work stably and that it has a better integration property and stronger signal when compared to a UV-lamp ion source.

To meet the demand for curvature measurements in the fields of intelligent biomedical equipment and soft robotics, among others, a flexible curvature sensor based on a polyvinyl chloride (PVC) and silicone composite substrate was proposed and has been designed. Firstly, a fiber Bragg grating (FBG) sensor was embedded into a silicone film, which was pasted onto the surface of a PVC substrate. Then, calibration experiments were carried out to evaluate the reflection spectrum and wavelength shift of the sensor. Finally, the sensitivity and repeatability of the sensor based on the composite and silicone substrates were tested experimentally. The experimental results show that the sensitivity and repeatability of the FBG curvature sensor can be improved by using a PVC-reinforced substrate. The maximum sensitivity of the FBG sensor with the composite substrate is 245.5 pm/m-1 and its deviation index is less than 3%. The sensor has wide application prospects in the fields of soft robotics and biomedical curvature measurements.

For quick adjustment of image brightness during skin imaging with reflectance confocal microscopy, an adaptive brightness adjustment method was proposed. The association between laser power control voltage and image brightness was established by experiments. Images can have two types of brightness: extreme and moderate. Using segmental adjustment, brightness of the initial image could be quickly changed from extreme to moderate. Finally, the optimal brightness was obtained using linear compensation. Real-time imaging of skin tissues at different depths and locations can show if the initial image is too bright, too dark, or of moderate brightness. Subsequently, quick adjustment of the brightness can be achieved. The number of iterations is 2-3, and the optimal image brightness is approximately 70. The results show that this method is fast and can effectively meet the needs of skin imaging with reflectance confocal microscopy.

To measure transparent parallel plates more easily and accurately, a phase recovery method based on the region growing algorithm and Fourier transform for single three-surface interference fringes was proposed. Through the Fourier transform, the three-surface interference fringe pattern was changed from the spatial to the spectral domain. Because the interference fringes of different surfaces have different positions in the spectral domain, the appropriate regions were extracted by changing the parameters in the region-growing algorithm, and the final surface was obtained. By this method, the planar shapes of the front and rear surfaces of the transparent parallel plate can be simultaneously obtained from a single three-surface interference fringe pattern. From an error analysis of the surface shapes obtained by the algorithm, a superimposed and separated double-surface interferogram was compared with the original three-striped graph to obtain the corresponding error distribution graph. The accuracy of the algorithm was improved through the error distribution graph. A comparison of the obtained surface shapes with that obtained by a Zygo interferometer reveals that the method had high measurement accuracy with a phase extraction error PV value of less than 0.12λ and a Root Mean Square(RMS) value of less than 0.065λ. A verification of the repeatability shows that the repetition rate is reliable, and the degree is better than λ/100. The measured surface shape approximated the real surface shape of the object, and the measurement method proved to be simpler than the original method.

To treat corneal dilatation diseases caused by keratoconus safely and effectively and to reduce manual alignment errors during surgery, an optical system for a corneal cross-linking surgical device was designed in this study. First, based on the requirements of corneal cross-linking surgery related to spot size, uniformity, and working distance, an illumination system was designed based on the principle of uniformation of the compound eye lens array. Second, an infrared lens was designed that was imaged by the human eye with a working distance of 175 mm and a magnification β of -4.2. The aforementioned design was then processed, a prototype of the corneal cross-linking device was built, and the designed optical system was tested experimentally. Experimental results show that the UV illumination light path is 65 mm, output spot diameter is 9 mm, and uniformity is 90.2%, which are comparable to those of similar instruments abroad. The infrared imaging light path can provide clear and quality images for tracking and positioning the human eye during a surgical operation. The optical system of the corneal cross-linking device designed in this study has the characteristics of a simple structure; further, it is low cost, exhibits good performance, and can well meet surgical requirements.

Axial symmetric curved shell resonators are among the most-widely used resonators because of their high symmetry, robustness, and reliability. However, the fabrication of this kind of resonator is based on newly developed three-dimensional (3D) microelectromechanical system technologies, making it difficult to fabricate. Polysilicon shell resonator is suitable for batch fabrication owing to its compatibility with the materials and fabrication technologies used in the IC industry, which is of high value and should be studied thoroughly. A 3D polysilicon shell resonator with high symmetry was produced using silicon cave as its mold, and the fabrication process was designed and tested experimentally. The cave was formed by isotropic etching of silicon, using a mixture of HF/HNO3/CH3CHOOH with bulk ratio 15∶10∶75 as the etchant. The temperature of the etchant was controlled using a water bath to ensure that the speed of the etching does not change abruptly. The level of the wafer was maintained by a clamp with which the wafers position could be adjusted freely. The abovementioned measures ensured that the silicon caves had good properties, especially the symmetry and roughness. Then, 3D polysilicon shells with diameters ranging from 0.8 to 1.3 mm were fabricated, with the smallest roundness less than 0.4%. The roughness of the shell was less than 1 nm. The resonant properties of the fabricated shells were investigated using noncontact characterization methods facilitated by a laser Doppler vibrometer. A mechanical quality (Q) of 14 365 at 28 kHz was obtained in vacuum with a pressure of 0.2 Pa. By adjusting the bias voltage and actuated voltage, the mode-matching situation was achieved, and the relative frequency mismatch between the two degenerate four-node wineglass modes was reduced to zero.

To achieve non-invasive blood glucose in vivo detection, solving common problems such as low measurement sensitivity, large interference of excitation source fluctuation, and serious patient temperature interference is first necessary. In this study, a new method based on temperature compensation for differential photoacoustic measurement was proposed, which can greatly suppress the influence of temperature. Two identical photoacoustic cells were used, one for accommodating the blood to be measured, the other for pure water. Measured and reference photoacoustic signals are respectively obtained. First, the temperature coefficient of the two photoacoustic signals is determined by changing the liquid temperature of the two photoacoustic cells. Then, the error of temperature in the two photoacoustic signals are separately compensated and corrected to eliminate the interference of temperature on the experimental results. Finally, the intensity of one photoacoustic signal is divided by that of the other photoacoustic signal to suppress the influence of laser intensity fluctuation. Based on this procedures the study used tissue engineered skin to simulate a human skin environment and explored the skins permeability to laser and photoacoustic signals. The results show that the R2 of linear fitting between glucose photoacoustic signal intensity and glucose concentration under a low concentration was 0.970 6, thereby proving the feasibility of this method for use in practical applications. The results also show that the average transmittance of the simulated skin to laser was 53.88%, and the average transmittance of the simulated skin to the photoacoustic signal was 9450%. The results of this study can provide a useful reference for the noninvasive detection of blood glucose.

During high-power laser treatment, protection of the epidermis and normal tissues from thermal damage is critical to ensure safety and effectiveness of the process. In this investigation, medical 134a cryogen with high cooling performance was used, and a high-pressure storage tank, an airtight transmission line, a high-speed atomized spray device, and an electronic control system were designed as part of a transient spray cooling system combined with laser therapy for different output timings to cool the skin and tissue in real-time. By studying the relationship between the spraying time, jet distance, and temperature changes of materials that are similar to skin, the cooling effect of the device was evaluated. The experimental results show that the tissue temperature can be reduced from 40 ℃ to 60 ℃ in 20 ms to 50 ms. The biological compatibility, pressure resistance, and sealing of the cooling system met the requirements of medical device registration. The system was combined with a high-power 1 450 nm semiconductor laser to treat facial acne in a clinical setting, and the total effective rate for 189 patients with mild-to-moderate acne is 87.3% after four treatments without thermal damage. It is possible to combine the transient spray cooling system with various laser devices to improve the safety, effectiveness, and scope of existing laser treatments.

Biometrics is becoming more and more important in the diagnosis and treatment of ophthalmic diseases. Monitoring the axial length of children and adolescents can help prevent and treat myopia, and the ophthalmic diseases that it causes. The accurate measurement of eye axial parameters is an important factor in visual quality that affects postoperative patients with eye diseases. In order to measure the parameters of the eye axis, the eye axis measurement method based on the time domainlow-coherence technique of time domain is presented. The prototype for high-precision and non-contact measurement is developed and the corresponding experiments are conducted. Using a combination of low-coherence interference technique and long coherent interference ranging technology, a fiber-optic low-coherence tomography measurement system is built using time-domain mechanical scanning. The repeatability error of standard lens thickness and mirror spacing measurements is less than 0.3 μm. In the experimental measurement of fish-eye axis parameters, the structure of the cornea, lens, and retina of the fish eye was clearly tested. The stability and repeatability of the system meets the design requirements. The tomographic measurement experiment on fish eyes successfully verified that the system can be used for the measurement of animal eye axis parameters.

Signals of interest can be affected by various types of noise during the acquisition of photoplethysmography data. To address this problem, a denoising method based on the combination of Ensemble Empirical Mode Decomposition (EEMD) and wavelet threshold was proposed to reduce the noise associated with photoplethysmography signals. In this investigation, this approach was compared with EMD combined with wavelet denoising. Initially, an algorithm applied EEMD to the signal, which was decomposed into a limited number of Intrinsic Mode Functions (IMF). Then, it performed a correlation calculation on the components, followed by wavelet threshold denoising on the noise-containing components. Finally, the signal was reconstructed. The original signal was measured using the stm32 platform with a MAX30100 sensor. The experimental results show that the method can effectively remove high-frequency noise and baseline drift in photoplethysmography. After noise reduction, the signal-to-noise ratio is 34.09 and the root mean square error is 1.99, which improved the signal quality. This new approach facilitates accurate monitoring of photoelectric volume pulse wave signals.

Clinical studies have shown that fluorescent molecular imaging technology is extensively utilized in intraoperative navigation, tumor boundary recognition, in vivo microscopic pathology diagnosis, etc. However, identification of tumor boundaries through in vivo biopsy remains a challenging task owing to the slight discrepancy between tumor tissue and surrounding normal tissue in optical imaging. To better distinguish tumor tissue and observe histopathology in clinical examination, a dual-mode switching endomicroscopic system was proposed in this paper, which consisted of wide-field imaging for surgical navigation and microscopic imaging for performing tumor boundary recognition. The system employed sodium fluorescein as a fluorescent molecular probe and an in-house developed blue LED with high-brightness as an excitation source. Fast switching between two modes was an advantageous design for clinical surgery to effectively determine benign and malignant tumors during in vivo microscopic pathology analysis. This paper examined the feasibility of the dual-mode imaging system for mouse liver inspection in vivo. The experimental results show that dual-mode imaging can identify tissue color and boundary features with a resolution of 4.4 μm. The system can meet the clinical demands of real-time surgical navigation and microscopic pathological diagnosis of in vivo tumors.

The determination of coagulation parameters is of crucial significance in the guided treatment of anticoagulant drug users and patients with liver diseases. Considering the challenges associated with commercial coagulation detection instruments such as high cost and complex operation, a MWCNT-enhanced screen-printed electrochemical sensor was developed for coagulation measurement. Initially, the measurement of thrombin substrate cleaved by thrombin was used to evaluate the feasibility of prothrombin time (PT) detection by chronoamperometry. Then the plasma PT parameters were measured and the results were validated using the SYSMEX CS 5100 optical coagulator. The response intensity of a MWCNT electrochemical sensor in thrombin validation experiments increase by (36±1)% compared with a general electrochemical sensor and the peak time coefficient of variation and peak current coefficients of variation are 2.99% and 3.27% respectively. The testing of PT values of different blood samples clearly shows discrimination. Three groups of blood samples are selected for repeated PT parameter measurements and the coefficients of variation are 2.26%, 322%, and 2.96% respectively. The linear fitting decision coefficient R2 is 0.986 for clinical results. The MWCNT screen-printed electrochemical sensor for PT testing has good repeatability and consistency, is easy to mass produce, reduces the cost of coagulation measurement, and is suitable for measurement in many circumstances. As such, this sensor has great potential in the field of point-of-care testing.

A non-contact respiratory and heart rate monitoring system was designed to monitor bedridden patients. Initially, according to the mechanical properties of the cardiac ejection contraction process, piezoelectric ceramic sensors with high sensitivity and good stability were selected to acquire ballistocardiography (BCG) signals. The collected signal was then desiccated, filtered and amplified; it was then digitized to obtain a heart impact diagram. A respiratory signal was then extracted from the cardiogram with smooth filtering, and the respiratory rate signal was obtained via an FFT transformation. The respiratory envelope and high-frequency interference of the BCG signal were removed using a band-pass filter, and the j-wave peak measurement of the BCG signal was obtained to calculate the heart rate. Finally, to verify the accuracy and consistency of the system, it was compared with respiratory data collected by BIOPAC and ECG signals. The respiratory error rate of the system is less than 4.5% and the heart rate error is 9.7%. A Bland-Altman analysis indicates that the heart rate measurement and accuracy computed by the monitoring system are consistent with those of BIOPAC.

To realize the initial design and experimental verification of wearable flexible electronics, an electronic rapid preparation method based on “cutting and pasting” was proposed. First, a micro-nano patterning process based on laser cutting was presented by a comparison with photolithography and inkjet printing processes. The patterned film structure was then transferred to an elastic substrate by adjusting the adhesion of a polydimethylsiloxane (PDMS) substrate to control the energy release rate. To ensure a close fit between the metal electrode and the flexible substrate, the overall structure was packaged by PDMS. Finally, a multichannel physiological signal acquisition system was built to enable electrophysiological testing and medical exploration. Compared with the traditional flexible electronic processing technology, the proposed method was more efficient and cheaper. In addition, the flexible electronic sensor was in conformal contact with skin and generated a stable signal. This investigation outlines the preliminary foundation and initial design for flexible electronics and their industrial applications.

To assist unattended fundus examination equipment in automatically performing fundus examinations under different lighting environments, an automatic pupil center location and alignment device was developed and a circle approximation algorithm was proposed to automatically locate the pupil center. First, an image was preprocessed by binarization and contour extraction, and a filling algorithm was used to eliminate the influence of noise and speckle for follow-up processing. The circle approximation algorithm proposed in this study was subsequently utilized to accurately locate the pupil center. Finally, the identified location of the pupil center was used to control the stepper motor to move the two-dimensional platform and align the image acquisition and pupil centers. To evaluate the efficiency of the proposed algorithm, the location accuracy and calculation rate were compared with those of the traditional and improved Hough circle algorithms. The precision and average consumption time of the proposed algorithm are 93.33% and 95.67 ms, respectively. Compared to that of the traditional and improved Hough circle algorithms, the precision of the proposed method improve 3.5 and 2 times, respectively, and the average consumption time is reduced by 68.86% and 63.11%, respectively. Experimental results indicate that the proposed system significantly improved the accuracy and calculation rate of automatic pupil location and alignment under conditions in which the illumination parameters cannot be strictly controlled. In summary, the proposed system is able to meet the real-time, accuracy, and robustness requirements of unattended fundus examination equipment, which has great significance for its popularization.

Molecular interaction detection is a hot topic in the fields of food safety detection, clinical cancer pathological screening, and other areas of research. To realize real-time and rapid detection of interactions between biomolecules, a molecular interaction detection system based on a fiber biosensor was designed in this study. The coupling structure of a self-focusing lens and quartz fiber was adopted to improve the coupling efficiency of optical transmission between the light source and interference light. A STM32 microprocessor was used as the main controller to realize data acquisition, 3D transmission mechanism control, constant temperature oscillation control, and other functions. Finally, the designed and BLItz molecular interaction detection systems were used to detect the different concentrations of immunoglobulin IgG and protein A, respectively. The binding and dissociation reactions of the IgG molecule and antigen molecule protein A were detected in real time. The experimental results show that the detection limit of the system could reach 10 μg/mL, and the repeatability CV value was less than 6%, which was close to that of the BLItz. The designed system has the advantages of high automation, no need for cleaning, no cross contamination in the detection process, and low cost. Therefore, it can meet the needs of pharmacokinetics research.

Graphene (GR) has excellent physical and chemical properties as a revolutionary material, and its excellent electrical conductivity is critical in developing coagulation electrochemical sensors. Currently, large coagulation testing instruments are complicated to operate and time-consuming, and few point-of-care tests exist for activated partial thromboplastin time (APTT) indicators. To solve this problem, designing and manufacturing a GR-modified electrochemical sensor based on screen-printing technology, which can be used for APTT index detection, is necessary. In this study, the feasibility of chronoamperometry to detect the time principle of activated partial thromboplastin was verified by a thrombin-cleaving thrombin substrate assay. The plasma-activated partial thromboplastin time parameter was measured, and the measurement results were verified using a SYSMEX CS 5100 optical coagulation instrument. The experiments showed that the screen-printed GR-modified electrode had good consistency, and its impedance test coefficient of variation is 2.71%. In the thrombin experiment, the current response intensity of the GR-modified electrochemical sensor was increased by 16 ± 1% as compared to the electrochemical sensor before modification, and the repeated peak time and peak current coefficient of variation are 3.29% and 3.13%, respectively. The APTT values of the three groups of blood samples were selected to show clearly the degree of discrimination, and the peak time variation coefficients of the three groups of APTT repeat experiments are 3.20%, 3.25%, and 2.84%, respectively. The experimental results are linearly fitted with the clinical results of the hospital. R2 is 0.978. The GR-modified enhanced electrochemical sensor showed good repeatability in the APTT test and thus has the potential for immediate detection in a variety of situations.

To address the problem of low detection accuracy in the traditional method of seed-breathing CO2 concentration measurement, a seed-breathing measurement system based on tunable diode laser absorption spectroscopic technology was proposed to meet the needs of seed-breathing CO2 concentration measurements. First, the system was designed to consist of a seed-breathing container, a distributed feedback laser and control circuit, photoelectric conversion and an amplification circuit, a data acquisition circuit, and upper computer software. The space volume of the seed breathing container was 1.5 L, the laser source was in the 2 004-nm band, and the light path of the multiple reflection cell was 16 m. Then, based on Lamberts law and wavelength modulated absorption spectroscopy, the concentration of CO2 produced during seed respiration could be retrieved in real time using second harmonics. The stable repeatability of the CO2 concentration measurement in seed respiration is 0.033%, the linear fitting degree of CO2 concentration is 0.999 38, and the detection limit of CO2 concentration is 1.7×10-6. The change curve of 20-g maize seed respiration is obtained by testing waxy maize seeds. The amount of change in waxy maize seed respiration after 12 h is 2 750.5×10-6, and the respiration rate is 229.2×10-6/h. Experimental results show that the system can solve the inability for continuous measurement of CO2 concentration in seed respiration and the low precision of concentration detection.

Image guidance plays a major role in precision radiotherapy. Because conventional X-ray image guided techniques used in radiotherapy deliver additional doses to patient, an image guided radiation therapy (IGRT) technique using conventional video cameras that does not cause harm to the patient was investigated in this study. Three conventional video cameras were installed in different directions to acquire real-time images. The backgrounds of the images were deleted using an adaptive background removal algorithm designed in this study, and then the region of interest was obtained. Real-time patient positioning information could be achieved using an oriented FAST and rotated BRIEF algorithm that we modified. Respiratory signals were derived from the real-time images of the conventional video cameras using an algorithm we designed. A plastic patient model immobilized with a thermoplastic shell on a simulation couch was used to verify the accuracy and feasibility of our method. Test results show that the position and angle offset errors identified with our system are less than 1 mm and 1°, respectively. A respiratory motion simulator is designed and used to test the respiratory signal acquirement algorithm we designed. The time and amplitude conformity of the respiratory signals between the setting and acquirement is better than 96%. In our laboratory tests, the developed IGRT technique is shown to satisfy the requirements of image guided radiotherapy.