Socioeconomic status affects amputation and mortality rates in necrotizing fasciitis patients.

PURPOSE: Necrotizing fasciitis (NF) is a rare, but rapidly progressing bacterial infection of the subcutaneous tissues and muscular fascia with high rates of morbidity and mortality. Our study aims to determine if socioeconomic status (SES) is a predictor of outcomes in NF. METHODS: A retrospective review was conducted of patients diagnosed with NF at our institution. Demographic information, insurance status, medical and surgical history, vitals, ASA score, blood laboratory values, surgical procedure information, and outcomes prior to patient discharge were collected. Patient zip codes were utilized to obtain median household incomes at the time of the patient's surgical procedure to determine SES. Patients without complete data in their medical record were excluded. Initial descriptive statistics and logistic regression models were performed. RESULTS: We identified 196 patients (mean age 50.13 ± 13.03 years, 31.6% female) for inclusion. Mortality rate was 15.3% (n = 30) and 33.7% (n = 66) underwent amputation. Mortality rate was not significantly different across income brackets. Lower income brackets had higher rates of amputation than higher income brackets (p < 0.05). A logistic regression models showed the rate of amputation decreases by 29% for every $10,000 increment in median household income and ASA score decreased by 0.15 units for every $10,000 increase in median household income. CONCLUSIONS: Amputation rates in cases of NF are significantly higher in lower SES groups than higher SES groups. Patients with perivascular disease in lower SES groups were more likely to experience serious complications of NF than their counterparts in higher SES groups.

Olecranon Tendo-Osseous Allograft Reconstruction for Complex Extensor Mechanism and Bone Loss at the Elbow.

PURPOSE: The purpose of this study was to present the results of olecranon tendo-osseous allograft (OTOA) reconstruction for patients with an irreparable extensor mechanism from prior trauma or failed total elbow arthroplasty (TEA). METHODS: A retrospective review was performed of all patients with extensor mechanism loss after trauma or failed TEA who were treated with an OTOA to supplement fracture fixation or elbow arthroplasty, as indicated. Primary outcome measures were successful healing of the allograft, restoration of the extensor mechanism function, and Mayo Elbow Performance Scores (MEPS) at the most recent follow-up. Secondary outcomes included patients' active range of motion and unplanned operative interventions. RESULTS: Nine patients had extensor mechanism and proximal ulna loss as a result of prior TEA, acute trauma, or failed surgeries for prior trauma. All but one had undergone multiple prior surgeries. The mean follow-up was 27 months (6-60 months). At the final follow-up, patients reported MEPS of 92 (80-100). All patients regained active triceps extension (strength 3-5/5). Mean final range of motion was 16° (0° to 45°) extension, 124° (70° to 150°) flexion, 56° (45° to 80°) pronation, and 60° (40° to 80°) supination. Eight (89%) of the nine patients had a radiographically healed graft at the latest follow-up, of which four healed without notable complications or further surgical intervention. Complications included radial/ulnar nerve palsy, allograft olecranon stress fracture, deep infection, wound complications, instability, and complications related to the TEA prosthesis. CONCLUSIONS: In the setting of elbow reconstruction in which there is inadequate triceps tendon and/or olecranon bone stock to perform internal fixation and/or revision arthroplasty, OTOA may supplement elbow reconstruction, albeit with high rates of complications. A triceps-olecranon allograft, combined with either internal fixation or TEA, is a potentially useful salvage procedure for managing bone loss and an irreparable extensor mechanism deficit at the elbow. LEVEL OF EVIDENCE: Therapeutic V.

The evaluation, classification, and management of septic arthritis of the shoulder: the comprehensive shoulder sepsis system.

BACKGROUND: Septic arthritis of the shoulder is distinctly challenging to diagnose and treat. Guidelines for appropriate workup and management are limited and do not account for the variations in clinical presentation. The purpose of this study was to present a comprehensive and anatomically based classification system and treatment algorithm for septic arthritis of the native shoulder joint. METHODS: A multicenter, retrospective analysis of all patients treated surgically for septic arthritis of the native shoulder joint was performed at 2 tertiary care academic institutions. Preoperative magnetic resonance imaging and operative reports were used to classify patients as having 1 of 3 infection subtypes: type I, confined to the glenohumeral joint; type II, extra-articular extension; or type III, concomitant osteomyelitis. On the basis of these clinical groupings of patients, the comorbidities, types of surgical management, and outcomes were analyzed. RESULTS: Sixty-five shoulders in 64 patients met the inclusion criteria for the study. Of these infected shoulders, 9.2% had type I infections, 47.7% had type II, and 43.1% had type III. Age and the time between symptom onset and diagnosis were the only significant risk factors for the development of a more severe infection. Fifty-seven percent of shoulder aspirates revealed cell counts below the standard surgical cutoff of 50,000 cells/mL. On average, each patient required 2.2 surgical débridements to eradicate the infection. Infections recurred in 8 shoulders (12.3%). Body mass index was the only risk factor for recurrence of infection. Of the 64 patients, 1 (1.6%) died acutely of sepsis and multiorgan system failure. CONCLUSION: We propose a comprehensive system for the classification and management of spontaneous shoulder sepsis based on stage and anatomy. Preoperative magnetic resonance imaging can help determine the severity of disease and aid in surgical decision making. A systematic approach to septic arthritis of the shoulder as a unique entity from septic arthritis of other large peripheral joints may lead to more timely diagnosis and treatment and improve the overall prognosis.

Joint aspiration and serum markers - do they matter in the diagnosis of native shoulder sepsis? A systematic review.

BACKGROUND: Septic arthritis of the native shoulder is traditionally diagnosed with the same strategies as knee or hip septic arthritis. However, septic arthritis of the shoulder is frequently a missed or delayed diagnosis. Reliance on aspiration and serum markers has been called into question recently. The purpose of this study was to conduct a systematic review investigating the value of joint aspiration and serum markers in the diagnosis of native shoulder joint sepsis. METHODS: PubMed/MEDLINE, Scopus, and the Cochrane Library were used in the systematic literature search from January 1, 1960, through January 23, 2021. The primary outcome was to report on the synovial white cell count of patients with native shoulder sepsis. Descriptive statistics using percentages, means, and intraclass correlation coefficient (ICC) values were used to summarize the results. RESULTS: Thirty-one studies, including 25 case series, one case-control, and five cohort studies with a total of 7434 native shoulder joints, were included. There was no standardized approach to diagnosing septic arthritis of the shoulder. Only 10 studies (32%) reported on synovial white cell count with the majority yielding aspiration counts greater than 50,000 cells/mm3, although one study was as low as 30,000 cells/mm3. CONCLUSIONS: The diagnosis of native shoulder joint sepsis lacks uniformity. Methods used to evaluate shoulder sepsis are heterogeneous and may lead to delays or misdiagnosis with devastating sequelae. Synovial white cell count is underutilized and may also present with a lower value than expected, which is likely related to the time interval between symptom onset and diagnosis.

Revisiting Amputation Rates in High-Pressure Injection Injuries.

Purpose: High-pressure injection injuries are a rare, and potentially serious, trauma that has historically been associated with high-amputation rates. This study aimed to assess the amputation rates, materials involved, and outcomes at a single institution. Methods: A retrospective analysis of 53 cases at a level-1 trauma center in South Central Texas between 2007 and 2023 was conducted. Patient demographics, injury details, materials injected, surgical interventions, complications, and follow-up data were collected and analyzed. Results: There was an amputation rate of 2.2. Latex-based paints showed more favorable outcomes when compared with grease injections and oil-based paints. There were also fewer reoperations and postoperative complications with latex-based paint injuries. Conclusions: The study signals the need for a re-evaluation of high-pressure injection injury outcomes, highlighting a more optimistic prognosis than previously thought. The evolution of materials in paints, especially latex-based paints, may have been associated with a lower rate of amputation than what was previously reported. Type of study/level of evidence: Prognostic IV.

Stress fractures of the hand and wrist in athletes.

Stress fractures of the upper extremity are reported less often than their lower extremity counterpart. This review aims to provide a comprehensive overview of an important and often missed diagnosis in pediatric athletes: hand and wrist stress fractures.

Evaluation of a Large Language Model's Ability to Assist in an Orthopedic Hand Clinic.

BACKGROUND: Advancements in artificial intelligence technology, such as OpenAI's large language model, ChatGPT, could transform medicine through applications in a clinical setting. This study aimed to assess the utility of ChatGPT as a clinical assistant in an orthopedic hand clinic. METHODS: Nine clinical vignettes, describing various common and uncommon hand pathologies, were constructed and reviewed by 4 fellowship-trained orthopedic hand surgeons and an orthopedic resident. ChatGPT was given these vignettes and asked to generate a differential diagnosis, potential workup plan, and provide treatment options for its top differential. Responses were graded for accuracy and the overall utility scored on a 5-point Likert scale. RESULTS: The diagnostic accuracy of ChatGPT was 7 out of 9 cases, indicating an overall accuracy rate of 78%. ChatGPT was less reliable with more complex pathologies and failed to identify an intentionally incorrect presentation. ChatGPT received a score of 3.8 ± 1.4 for correct diagnosis, 3.4 ± 1.4 for helpfulness in guiding patient management, 4.1 ± 1.0 for appropriate workup for the actual diagnosis, 4.3 ± 0.8 for an appropriate recommended treatment plan for the diagnosis, and 4.4 ± 0.8 for the helpfulness of treatment options in managing patients. CONCLUSION: ChatGPT was successful in diagnosing most of the conditions; however, the overall utility of its advice was variable. While it performed well in recommending treatments, it faced difficulties in providing appropriate diagnoses for uncommon pathologies. In addition, it failed to identify an obvious error in presenting pathology.

A component-based analysis of metabolic syndrome's impact on 30-day outcomes after hip fracture: reduced mortality in obese patients.

Introduction: Hip fractures are a common injury associated with significant morbidity and mortality. In the United States, there has been a rapid increase in the prevalence of metabolic syndrome (MetS), a condition comprised several common comorbidities, including obesity, diabetes mellitus, and hypertension, that may worsen perioperative outcomes. This article assesses the impact of MetS and its components on outcomes after hip fracture surgery. Methods: Patients who underwent nonelective operative treatment for traumatic hip fractures were identified in the 2015-2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Baseline characteristics between groups were compared, and significant differences were included as covariates. Multivariate regression was performed to assess the impact of characteristics of interest on postoperative outcomes. Patients with MetS, or a single one of its constitutive components-hypertension, diabetes, and obesity-were compared with metabolically healthy cohorts. Results: In total 95,338 patients were included. Patients with MetS had increased complications (OR 1.509; P < 0.001), but reduced mortality (OR 0.71; P < 0.001). Obesity alone was also associated with increased complications (OR 1.14; P < 0.001) and reduced mortality (OR 0.736; P < 0.001). Both hypertension and diabetes alone increased complications (P < 0.001) but had no impact on mortality. Patients with MetS did, however, have greater odds of adverse discharge (OR 1.516; P < 0.001), extended hospital stays (OR 1.18; P < 0.001), and reoperation (OR 1.297; P = 0.003), but no significant difference in readmission rate. Conclusion: Patients with MetS had increased complications but decreased mortality. Our component-based analysis showed had obesity had a similar effect: increased complications but lower mortality. These results may help surgeons preoperatively counsel patients with hip fracture about their postoperative risks.

Improved Outcomes in Operative Management of Concomitant Distal Radius and Scaphoid Fractures.

BACKGROUND: This study aims to investigate the characteristics of concomitant distal radius and scaphoid fractures and determine outcome differences of operative and nonoperative management. METHODS: A retrospective search of a level-1 trauma center's database over a 15-year period (2007-2022) for concomitant distal radius and scaphoid fractures in adult patients was completed. In all, 31 cases were reviewed for mechanism of injury, method of fracture management, distal radius fracture AO Foundation/Orthopaedic Trauma Association classification, scaphoid fracture classification, time to radiographic scaphoid union, time to motion, and other demographics. A multivariate statistical analysis was completed comparing outcomes in operative versus conservative management of the scaphoid fracture in these patients. Outcomes were defined as time to radiographic union and time to motion. RESULTS: In all, 22 cases of operative fixation of the scaphoid and 9 cases of nonoperative management of the scaphoid were reviewed. One case of nonunion was identified in the operative group. Operative management of scaphoid fractures resulted in a statistically significant reduction in time to motion (2-week reduction) and time to radiographic union (8-week reduction). CONCLUSIONS: This study demonstrates that operative management of scaphoid fractures in the setting of a concomitant distal radius fracture reduces the time to radiographic union and time to clinical motion. This suggests that operative management is ideal in patients who are good candidates for surgery and desire earlier return of motion. However, conservative management should be considered, as nonoperative care showed no statistical difference regarding union rates of scaphoid or distal radius fractures.

Medial Elbow Pain Syndrome: Current Treatment Strategies.

Medial elbow pain is a common presentation that can be a challenge to appropriately treat for the orthopedic surgeon. Causes include medial epicondylitis, ulnar neuritis, ulnar collateral ligament injury, flexor pronator strain, or snapping medial triceps. A good outcome is typically achieved with adequate treatment of tendon degeneration at the common flexor tendon origin. Mainstay treatment is nonoperative modalities such as stretching, rest, activity modification, therapy, and injections. If nonoperative management fails, intermediate interventions such as extracorporeal shockwave therapy, platelet-rich plasma injections, prolotherapy, and ultrasound-guided percutaneous tenotomy can be attempted. Surgical treatments are dictated based on the severity of the pathology, involvement of soft tissues, and concomitant pathology. Medial elbow complaints can be multifactorial and require a broad differential diagnosis. [Orthopedics. 2023;46(2):e81-e88.].

In-Hospital Mortality Risk and Discharge Disposition Following Hip Fractures: An Analysis of the Texas Trauma Registry.

Background: In-hospital mortality and discharge disposition following traumatic hip fractures previously reported in the literature, has mainly focused on a nationwide scale, which may not be reflective of unique populations. Objective: Our aim was to characterize demographics, hospital disposition, and associated outcomes for patients with the most common hip fractures. Methods: A retrospective study utilizing the Trauma Registry from the Texas Department of State Health Services. Patient demographics, injury characteristics, and outcomes, such as in-hospital mortality, and discharge dispositions, were collected. The data were analyzed via univariate analysis and multivariate regressions. Results: There were 17,104 included patients, composed of 45% femoral neck fractures (FN) and 55% intertrochanteric fractures (IT). There were no differences in injury severity score (ISS) (9 ± 1.8) or age (77.4 ± 8 years old) between fracture types. In-hospital mortality risk was low but different among fracture types (intertrochanteric, 1.9% vs femoral neck, 1.3%, P = .004). However, when controlling for age, and ISS, intertrochanteric fractures and Hispanic patients were associated with higher mortality (P < .001, OR 1.5, 95% CI 1.1-2.0). Uninsured, and Black/African American (P = .05, OR 1.2, 95% CI 1.1-1.3) and Hispanic (P < .001, OR 1.2, 95% CI 1.1-1.3) patients were more likely to be discharged home after adjusting for age, ISS, and payment method. Conclusion: Regardless of age, severity of the injury or admission hemodynamics, intertrochanteric fractures and Hispanic/Latino patients had an increased risk of in-hospital mortality. Patients who were uninsured, Hispanic, or Black were discharged home rather than to rehabilitation, regardless of age, ISS, or payment method.

Impact of COVID-19 on Elective Orthopaedic Surgery Outcomes During the Peak of the Pandemic, an Uptick of Complications: An Analysis of the ACS-NSQIP.

INTRODUCTION: Since the World Health Organization declared a pandemic in March 2020, COVID-19 has pressured the healthcare system. Elective orthopaedic procedures for American seniors were canceled, delayed, or altered because of lockdown restrictions and public health mandates. We sought to identify differences in the complication rates for elective orthopaedic surgeries before and atfter the pandemic onset. We hypothesized that complications increased in the elderly during the pandemic. METHODS: We conducted a retrospective analysis of the American College of Surgeons-National Surgical Quality Improvement Program database in patients older than 65 years undergoing elective orthopaedic procedures from 2019 (prepandemic) and April to December 2020 (during the pandemic). We recorded readmission rates, revision surgery, and 30-day postoperative complications. In addition, we compared the two groups and adjusted for baseline features with standard multivariate regression. RESULTS: We included 146,430 elective orthopaedic procedures in patients older than 65 years (94,289 before the pandemic and 52,141 during). Patients during the pandemic had a 5.787 times greater chance of having delayed wait time to the operating room (P < 0.001), a 1.204 times greater likelihood of readmission (P < 0.001), and a 1.761 times increased chance of delayed hospital stay longer than 5 days (P < 0.001) when compared with prepandemic. In addition, during the pandemic, patients were 1.454 times more likely to experience any complication (P < 0.001) when compared with patients prepandemic undergoing orthopaedic procedures. Similarly, patients were also 1.439 times more likely to have wound complication (P < 0.001), 1.759 times more likely to have any pulmonary complication (P < 0.001), 1.511 times more likely to have any cardiac complication (P < 0.001), and 1.949 times more likely to have any renal complication (P < 0.001). CONCLUSION: During the COVID-19 pandemic, elderly patients faced longer wait times within the hospital and increased odds of complications after elective orthopaedic procedures than similar patients before the pandemic.

Providing Orthopaedic Care to Vulnerably Underserved Patients: AOA Critical Issues.

ABSTRACT: Implementation of the Affordable Care Act has increased the number of Americans with health insurance. However, a substantial portion of the population is still considered underserved, including those who are uninsured, underinsured, and those who are enrolled in Medicaid. The patients frequently face substantial access-to-care issues. Many underlying social determinants of health impact this vulnerable, underserved population, and surgeons must understand the nuances of caring for the underserved. There are numerous opportunities to engage with this population, and providing care to the indigent can be rewarding for both the vulnerably underserved patient and their surgeon.

A Novel Hemiarthroplasty Design for Treatment of Post-traumatic Elbow Ankylosis and Distal Humerus Nonunion: A Case Report.

CASE: A 26 year old man sustained a blast injury to the right elbow, resulting in chronic distal humerus nonunion and post-traumatic ankylosis. After debridement and flap coverage, a custom distal humerus hemiarthroplasty construct with extramedullary orthogonal plating was used. Satisfaction and functional outcomes were maintained through 6 years of follow-up. CONCLUSION: This case presents a unique 1-stage surgical solution which demonstrates the potential for uncemented extramedullary hemiarthroplasty fixation with simultaneous compression plate osteosynthesis across a nonunion site. The potential for hemiarthroplasty designs to be linked to orthogonal plates preserves the intramedullary canal for future conversion to total elbow arthroplasty if necessary.

Socioeconomic status does not change decision-making in the treatment of distal radius fractures at a level 1 trauma center.

Objectives: To compare operative rates, total hospital charges, and length of stay between different socioeconomic cohorts in treating distal radius fractures (DRFs). Design: A retrospective cohort study. Setting: Large public level 1 trauma center. Patients: A retrospective search of all trauma activations over a 7-year period (2013-2020) yielded 816 adult patients diagnosed with DRF. Patients were separated into cohorts of socioeconomic status based on 2010 US Census data and insurance status. Intervention: DRFs were treated either nonoperatively using closed reduction and splinting or operatively using open reduction and internal fixation, closed reduction percutaneous pinning, or external fixator application. Main Outcome Measurements: Operative rates of DRF, total hospital charges, and length of stay. Results: Patients who were uninsured or in the low-income socioeconomic cohort had no significant difference in operative rates, total hospital costs, or length of stay when compared with their respective insured or standard income groups. Younger patients and those with OTA/AO type C, bilateral, or open DRFs were more likely to undergo operative intervention. Conclusions: This study demonstrates that low socioeconomic status based on annual household income and insurance status was not associated with differences in operative rates on DRFs, length of stay, or total hospital charges. These results suggest that outcome disparities between groups may be caused by postoperative differences rather than treatment decision-making. Although this study investigates access to surgical care at a publicly funded level 1 trauma center, disparities may still exist in other models of care. Level of Evidence: Prognostic Level III.

Use of Clindamycin for Necrotizing Soft Tissue Infection Decreases Amputation Rate.

OBJECTIVE: To identify the impact of clindamycin use on mortality and amputation rates in patients with necrotizing fasciitis. DESIGN: Retrospective review. SETTING: Level 1 trauma center, single-center study. PATIENTS/PARTICIPANTS: All patients from 2008 to 2019 with a diagnosis of necrotizing fasciitis. One hundred ninety patients were included in statistical analysis. INTERVENTION: Use of clindamycin in the initial antibiotic regimen in the treatment of necrotizing soft tissue infection. MAIN OUTCOME MEASUREMENTS: Amputation and mortality rates. RESULTS: Patients who received clindamycin had 2.92 times reduced odds of having an amputation when compared with their counterparts, even when American Society of Anesthesiologist scores, comorbidities, smoking, drug use, alcohol consumption, race, ethnicity, sex, and age were controlled for and regardless of other antibiotics started (P = 0.015). There was no significant difference in mortality rate between those patients who did and did not receive clindamycin as part of their initial antibiotic regimen (8.3% vs. 11.6%, respectively; P = 0.453). CONCLUSION: The use of clindamycin in the initial antibiotic regimen for treatment of NSTI was shown to significantly decrease rates of amputation but not mortality. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Fate of the Uninsured Ankle Fracture: Significant Delays in Treatment Result in an Increased Risk of Surgical Site Infection.

OBJECTIVE: To examine the impact of insurance status on access to orthopaedic care and incidence of surgical site complications in patients with closed unstable ankle fractures. DESIGN: Retrospective chart review. SETTING: Certified Level-1 urban trauma center and county facility. PARTICIPANTS: Four hundred eighty-nine patients with closed unstable ankle fractures undergoing open reduction and internal fixation between 2014 and 2016. INTERVENTION: Open reduction and internal fixation of unstable ankle fracture. MAIN OUTCOME MEASURES: Time from injury to presentation, time from injury to surgery, rate of surgical site infections, and loss to follow-up. RESULTS: A total of 489 patients (70.5% uninsured vs. 29.5% insured) were enrolled. Uninsured patients were more likely to be present to an outside hospital first (P = 0.004). Time from injury to presentation at our hospital was significantly longer in uninsured patients (4.5 ± 7.6 days vs. 2.3 ± 5.5 days, P < 0.001). Time from injury to surgery was significantly longer in uninsured patient (9.4 ± 8.5 days vs. 7.3 ± 9.1 days, P < 0.001). Uninsured patients were more likely to be lost to postoperative follow-up care (P = 0.002). A logistic regression analysis demonstrated that delayed surgical timing was directly associated with an increased risk of postoperative surgical site infection (P = 0.002). CONCLUSIONS: Uninsured patients with ankle fractures requiring surgery experience significant barriers regarding access to health care. Delay of surgical management significantly increases the risk of surgical site infections in closed unstable ankle fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

High-resolution spectral analysis of individual SERS-active nanoparticles in flow.

Nanoparticle spectroscopic tags based on surface enhanced Raman scattering (SERS) are playing an increasingly important role in bioassay and imaging applications. The ability to rapidly characterize large populations of such tags spectroscopically in a high-throughput flow-based platform will open new areas for their application and provide new tools for advancing their development. We demonstrate here a high-resolution spectral flow cytometer capable of acquiring Raman spectra of individual SERS-tags at flow rates of hundreds of particles per second, while maintaining the spectral resolution required to make full use of the detailed information encoded in the Raman signature for advanced multiplexing needs. The approach allows multiple optical parameters to be acquired simultaneously over thousands of individual nanoparticle tags. Characteristics such as tag size, brightness, and spectral uniformity are correlated on a per-particle basis. The tags evaluated here display highly uniform spectral signatures, but with greater variability in brightness. Subpopulations in the SERS response, not apparent in ensemble measurements, are also shown to exist. Relating tag variability to synthesis parameters makes flow-based spectral characterization a powerful tool for advancing particle development through its ability to provide rapid feedback on strategies aimed at constraining desired tag properties. Evidence for single-tag signal saturation at high excitation power densities is also shown, suggesting a role for high-throughput investigation of fundamental properties of the SERS tags as well.

Providing Hand Surgery Care to Vulnerably Uninsured Patients.

Economically vulnerable US patients are at risk for undertreatment of hand-related conditions as well as poorer outcomes. The cost of indigent care can be substantial to both the patients and their communities. Caring for these patients in a system that depends on inconsistent coverage requires a network of safety-net hospitals. To ensure that patients have access to care, the protection of safety-net hospitals should be prioritized when discussing federal and state funding allocation. On an individual scale, surgeons can also make changes in their practices to help find sustainable ways to care for indigent patients.

Self-assembly approach to multiplexed surface-enhanced Raman spectral-encoder beads.

We present a strategy for the synthesis of multiplexed spectral encoder beads based on combinations of different surface enhanced Raman (SERS) signatures generated by dye-functionalized Ag nanoparticle tags. A key problem in SERS-based multiplexing arises in balancing the competitive binding of different signal generating dyes to the nanoparticle surfaces, which leads to difficulty in generating final summation spectra by design. We avoid this complication by decoupling the formation of individual tags from multiplexing of their spectra by self-assembly of different tag combinations onto SiO(2) microbead supports via biotin-avidin binding. Linear combinations of individual nanoparticle tag spectra are generated in precursor solutions and are found to directly translate to the final encoder bead fingerprint spectrum in a 1:1 binding stoichiometry that preserves the original solution ratios. The result is an ability to multiplex spectral signatures in both frequency and intensity space to generate a large number of unique encoder signatures from a limited number of initial tag spectra. Raman microscopy of 75 individual beads shows that spectral response is highly uniform from bead-to-bead, making the encoder assemblies suitable for highly multiplexed bioassay applications and as model systems for cellular surface labeling studies for imaging and immunoassays.